Quines fases inclouen els assaigs clínics de medicaments?

Les fases dels assaigs clínics inclouen fases I, II i III, amb nombrosos individus i durades variades.

Quina recerca específica va ser destacada durant la conferència?

S'expliquen les recerques relacionades amb els anticossos antiamiloide per a l'Alzheimer.

Quins efectes i resultats tenen les teràpies amb anticossos monoclonals per a Alzheimer?

La teràpia amb monoclonal antibodi pot eliminar la placa amiloide al cervell, però té efectes secundaris avaluats segons el benefici potencial.

Quin és el benefici potencial d'eliminar l'amiloide en fases inicials de la malaltia?

És probable que pugui ajudar a reduir o retardar l'aparició dels símptomes.

L'eliminació de la placa amiloide significa immediatament un èxit total en el tractament de l'Alzheimer?

No, es necessita més temps per a avaluar els resultats clínics de benefici complet de la intervenció.

Les proves clíniques estudien la qualitat de vida dels pacients?

Són mesurades en molts assaigs per entendre el seu impacte, encara que els resultats poden variar entre pacients.

What’s New in Alzheimer’s Disease Clinical Trials?

01:09:58

https://www.youtube.com/watch?v=drBo5UnkKII

概要

TLDRDurant la conferència, es va discutir extensament la investigació i els assaigs clínics relacionats amb la malaltia d'Alzheimer, amb un enfocament especial en els anticossos antiamiloide. La Dra. Judy Heidebrank va explicar les diferents fases dels assaigs clínics que van des de la seguretat inicial fins a la comprovació de l'eficàcia dels tractaments, especialment centrant-se en el recurs als anticossos monoclonals per intentar eliminar la placa amiloide del cervell i tractar així els simptomatologia de l'Alzheimer. Es va esmentar que, tot i que s'ha vist que aquests tractaments poden eliminar amiloides, encara existeixen interrogants sobre quins beneficis clínics resultants ofereixen. Aquests assaigs han demostrat que poden retardar la progressió dels símptomes per uns quants mesos, tot i que presenten desafiaments pel que fa als efectes secundaris. En la gran discussió posterior, es va abordar la necessitat de futurs estudis que podrien oferir aproximacions més personalitzades i eficients per combatre la malaltia, així com l'impacte d'intervencions en la qualitat de vida dels pacients. També es va reflexionar sobre la importància de combinar diversos mètodes, com l’exercici i la interacció social, com una forma de reduir el risc d'aparició d'Alzheimer.

収穫

👩‍⚕️ La Dra. Judy Heidebrank va explicar les fases dels assaigs clínics sobre Alzheimer.
🧪 Es van discutir els anticossos antiamiloide com a tractament clau.
⚠️ Els tractaments poden eliminar amiloides però tenen efectes secundaris.
⏳ S'ha demostrat que poden retardar els símptomes durant mesos.
🔬 Encara no es coneix completament el benefici clínic final.
🧠 Hi ha diversos assaigs enfocat en prevenir símptomes en fases inicials.
🔍 Necessitem més estudis per confirmar els beneficis a llarg termini.
🏋️ L'exercici i la interacció social poden ajudar a reduir el risc d'Alzheimer.
💊 La personalització del tractament és un focus d'interès en la recerca.
📈 S'exploren maneres més realístiques d'administrar teràpies.

タイムライン

00:00:00 - 00:05:00
La presentació s'inicia amb la introducció de la Dra. Judy Heidebrank, especialista en proves clíniques en malalties relacionades amb la demència, especialment l'Alzheimer. Ha participat en proves que van des de fases inicials fins a avançades centrades en la prevenció i tractament de la demència d'Alzheimer.
00:05:00 - 00:10:00
Es descriuen les diferents fases d'assaigs clínics per a medicaments, des de la fase 1 on es prova la seguretat en humans, fins a la fase 3 que avalua l'eficàcia sobre una mostra més gran i amb comparació placebo. Es destaca la importància de distingir entre les proves dirigides específicament a l'Alzheimer.
00:10:00 - 00:15:00
En aquest segment es revisen els assaigs clínics que utilitzen anticossos monoclonals per tractar la demència d'Alzheimer, centrant-se en l’eliminació de les plaques d’amiloide al cervell. Aquestes plaques són un segell distintiu de l’Alzheimer i els anticossos poden ajudar a eliminar-les.
00:15:00 - 00:20:00
Un dels medicaments, l’aducanumab, va ser aprovat pel seu efecte en l’eliminació de l’amiloide, però no tots els estudis han confirmat el benefici clínic significatiu, i hi ha sol·licituds per realitzar estudis addicionals per determinar el seu veritable impacte en la progressió de la malaltia.
00:20:00 - 00:25:00
Esmenta l’acceleració en l'aprovació del FDA per a educanumab, condicionada a una base biològica més que a beneficis clínics contundents, la qual cosa implica necessitar més estudis que determinin si l’eliminació de l’amiloide tradueix realment en beneficis clínics palpables.
00:25:00 - 00:30:00
Un nou medicament, la canemab, es vertebrarà en una nova fase d'aprovació després d'haver demostrat disminuir l'acumulació d'amiloide i presentar una reducció de la progressió de la demència en comparació al placebo, malgrat els efectes secundaris.
00:30:00 - 00:35:00
La discussió destaca que, tot i que s'han notat algunes millores en la reducció de la placa amb la canemab i d’altres compostos similars, els efectes adversos mostren riscos que han de ser monitoritzats rigorosament, sobretot en pacients amb certs factors genètics de risc.
00:35:00 - 00:40:00
Hi ha notícies de nous estudis que investiguen teràpies alternatives que permetin una administració més pràctica i eficient, com ara formulacions subcutànies per facilitar el tractament de pacients amb Alzheimer.
00:40:00 - 00:45:00
Es parla dels estudis en marxa que tracten de prevenir les símptomes d’Alzheimer en pacients asimptomàtics amb plaques d’amiloide mitjançant teràpies en fases avançades com a part d'una aproximació preventiva.
00:45:00 - 00:50:00
S'aclareix la correlació entre Tau i la pèrdua funcional cognitiva, i es parla de noves investigacions que apunten a plaques de Tau com a objectiu terapèutic, tot i que les proves inicials han mostrat eficàcia limitada fins al moment.
00:50:00 - 00:55:00
La investigació sobre la Tau també contempla estudis curiosos sobre animals en hibernació que poden oferir noves perspectives sobre com el cervell pot gestionar la patologia de la Tau.
00:55:00 - 01:00:00
Les proves clíniques també contemplen altres vies de tractament no centrades en la placa o Tau, incloent intervencions de tipus comportamental o relacionades amb el benestar general que podrien influir positivament en la progressió de la malaltia.
01:00:00 - 01:09:58
Finalment, es repassen els numerables estudis en marxa que busquen comprendre millor el mecanisme de l’Alzheimer, amb la finalitat d'identificar nous objectius terapèutics i millorar la qualitat de vida dels pacients.

よくある質問

Qui va ser la ponent de l'esdeveniment?
La Dra. Judy Heidebrank.
Quines fases inclouen els assaigs clínics de medicaments?
Les fases dels assaigs clínics inclouen fases I, II i III, amb nombrosos individus i durades variades.
Quina recerca específica va ser destacada durant la conferència?
S'expliquen les recerques relacionades amb els anticossos antiamiloide per a l'Alzheimer.
Quins efectes i resultats tenen les teràpies amb anticossos monoclonals per a Alzheimer?
La teràpia amb monoclonal antibodi pot eliminar la placa amiloide al cervell, però té efectes secundaris avaluats segons el benefici potencial.
Quin és el benefici potencial d'eliminar l'amiloide en fases inicials de la malaltia?
És probable que pugui ajudar a reduir o retardar l'aparició dels símptomes.
L'eliminació de la placa amiloide significa immediatament un èxit total en el tractament de l'Alzheimer?
No, es necessita més temps per a avaluar els resultats clínics de benefici complet de la intervenció.
Les proves clíniques estudien la qualitat de vida dels pacients?
Són mesurades en molts assaigs per entendre el seu impacte, encara que els resultats poden variar entre pacients.

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オートスクロール:

00:00:11
I think we're going to have quite a few
00:00:13
people here today so that's exciting
00:01:17
all right well I think we'll go ahead
00:01:19
and get started
00:01:20
um thank you all so much for coming to
00:01:24
our speaker series today and I am
00:01:27
honored to introduce our speaker Dr Judy
00:01:30
heidebrank is the director of the
00:01:33
neurology cognitive disorders clinic and
00:01:35
is the co-leader of the clinical core of
00:01:38
the Michigan Alzheimer's disease
00:01:39
Research Center
00:01:41
she has been involved in collaborative
00:01:43
clinical trials and dementia for over 20
00:01:46
years including phase one through three
00:01:49
studies focusing on the prevention and
00:01:52
treatment of Alzheimer's Dementia in
00:01:55
addition she has led the University of
00:01:57
Michigan's participation in the
00:01:59
Alzheimer's disease neuroimaging
00:02:01
initiative since the Inception of this
00:02:04
longitudinal observational study of
00:02:06
brain images and other biomarkers in the
00:02:10
progression from normal aging to
00:02:12
dementia I am very pleased to
00:02:16
um have Judy High to bring with us today
00:02:20
well good afternoon everyone and thank
00:02:22
you for joining me to hear this update
00:02:24
about clinical trials in Alzheimer's
00:02:27
disease you probably know from the news
00:02:29
that there have been lots of reports
00:02:31
regarding recent information from
00:02:34
clinical trials and Alzheimer's disease
00:02:36
so this topic could not have been more
00:02:38
timely even if it did mean updating my
00:02:41
slides literally on a weekly basis as
00:02:43
some of these news releases are coming
00:02:45
in so here's what I'd like to go over
00:02:48
today I'll just start with a little bit
00:02:50
of background information about clinical
00:02:53
trials and the focus of the ones that
00:02:55
I'm going to review today and then spend
00:02:58
a fair amount of time about the trials
00:03:00
looking at the anti-amyloid antibodies
00:03:03
because those have really been in the
00:03:05
news in particular lately and then I'll
00:03:07
just give some brief highlights about
00:03:09
some other clinical trials that aren't
00:03:11
necessarily targeting amyloid or using
00:03:13
the anti-amyloid antibodies
00:03:16
so just as a reminder what I'm going to
00:03:19
focus on today are clinical trials
00:03:21
looking at potential treatments for
00:03:24
Alzheimer's disease but Alzheimer's
00:03:27
disease is one of many potential causes
00:03:30
of dementia so dementia is a syndrome
00:03:33
where individuals experience changes in
00:03:35
their thinking abilities that impact
00:03:37
their daily activities Alzheimer's is
00:03:39
the most common cause of dementia
00:03:41
particularly later in life but it's not
00:03:43
the only cause of dementia so some of
00:03:46
the other causes of dementia are
00:03:47
pictured here and it's important to pay
00:03:51
attention whenever you're hearing
00:03:52
information about clinical trials to
00:03:54
know whether the trial was focused
00:03:56
specifically on persons with Alzheimer's
00:03:58
as a cause of their Dementia or kind of
00:04:00
impairment or whether it was a different
00:04:02
type of dementia because treatments
00:04:04
against the specific pathology of
00:04:06
Alzheimer's like the plaques and Tangles
00:04:08
wouldn't necessarily be expected to have
00:04:10
an impact on a different type of
00:04:12
dementia that doesn't have plaques and
00:04:13
Tangles for example some studies though
00:04:16
might look more Broad readily at ways to
00:04:18
protect the brain from loss of nerve
00:04:20
cells in the setting of any number of
00:04:22
dementia causes so some potential
00:04:24
therapies might be studied in more than
00:04:26
one type of dementia but again I'm going
00:04:28
to focus today on clinical trials
00:04:30
related to Alzheimer's disease
00:04:33
and so you heard Stephanie mention that
00:04:35
at the University of Michigan we've been
00:04:37
involved in trials in different phases
00:04:40
what are these clinical trial phases
00:04:42
that she mentioned so before any type of
00:04:46
medication is reviewed for approval by
00:04:49
the Food and Drug Administration it
00:04:51
typically goes through a series of
00:04:53
phases of clinical trials and they are
00:04:57
ordered numerically phase one phase two
00:04:59
and phase three and they basically
00:05:02
expand in terms of the numbers of
00:05:04
individuals participate how long they're
00:05:06
being given the treatment and what type
00:05:09
of measurements are being looked at so
00:05:12
the first time a drug is given to a
00:05:14
human after it's gone through some early
00:05:16
studies in animals for example the first
00:05:19
round humans is a phase one trial and
00:05:22
the real question is here is this
00:05:24
medication safe it's been looked at in
00:05:26
animals we think it might be promising
00:05:28
for a particular disease but if it's
00:05:30
never been given to humans before we
00:05:31
just have to start out by saying is this
00:05:33
safe and how much can someone take how
00:05:36
long does it last in their body does it
00:05:39
need to be given every day every week
00:05:41
multiple times a day so these are very
00:05:43
early studies looking at how the drug
00:05:46
gets into the body where it goes how
00:05:47
long it lasts and are there any side
00:05:49
effects of any type so sometimes in
00:05:52
these initial phase one trials healthy
00:05:54
individuals are picked just to be able
00:05:56
to study the metabolism of the drug it
00:06:00
might be older adults if ultimately the
00:06:02
study is going to be used to if the drug
00:06:05
is going to be used to treat a condition
00:06:06
that's more common in older adults but
00:06:07
sometimes to begin with it's younger
00:06:09
healthy adults just to be able to see
00:06:11
how someone tolerates it how long it
00:06:14
lasts and really is it safe and at what
00:06:16
dose and duration so these might be
00:06:18
small numbers of individuals they may
00:06:21
all get the active drug there might not
00:06:23
be a placebo for comparison and
00:06:25
depending on the type of drug these
00:06:27
studies might just last a few days for a
00:06:29
few weeks
00:06:30
and as long as the medication looks like
00:06:33
it's safe and there's at least some
00:06:34
doses that look like they might be
00:06:37
useful I have to carry forward then a
00:06:39
phase two trial starts to introduce a
00:06:41
larger number of individuals these are
00:06:43
typically persons who have the condition
00:06:46
for which the treatment is being studied
00:06:48
and you still want to know is it safe
00:06:50
but this time individuals are given a
00:06:52
more standard dose over a longer period
00:06:54
of time to see again how do they
00:06:56
tolerate over a longer period of time
00:06:57
and is there some initial evidence that
00:06:59
it might be helpful for the condition
00:07:01
for which it's being studied so this
00:07:04
might have a few hundred patients and
00:07:06
they might be taking the intervention
00:07:08
for several months
00:07:09
with really trying to learn does this
00:07:11
drug look like it's potentially
00:07:13
beneficial and then sort of the pivotal
00:07:16
trial is at the phase three stage where
00:07:18
even more individuals are given the
00:07:21
medication often again with a placebo
00:07:23
group at this point phase two and phase
00:07:25
three typically have a placebo group so
00:07:27
you can compare if we're seeing
00:07:29
something is it because of the drug or
00:07:31
is it just by random chance to learn
00:07:33
that you really need to compare the
00:07:35
active drug versus a placebo and again
00:07:37
this would be many individuals over a
00:07:39
longer period of time to really answer
00:07:41
the overall question is there a benefit
00:07:44
to this treatment in this condition that
00:07:46
outweighs any potential risk so these
00:07:49
might be longer term trials many months
00:07:51
or even a few years just depending on
00:07:53
what type of condition is being studied
00:07:54
so today I'm going to focus on a lot of
00:07:58
the phase three information because
00:07:59
again that's sort of the pivotal stage
00:08:01
that aside is this drug ultimately going
00:08:04
to be helpful and potentially be
00:08:06
approved by by the FDA
00:08:08
foreign
00:08:09
so as I mentioned earlier a lot of the
00:08:12
trial information in the Alzheimer's
00:08:14
disease realm has been with compounds
00:08:17
that are targeting the amyloid plaque
00:08:20
buildup that happens in the brain when
00:08:22
someone develops Alzheimer's disease and
00:08:25
so there are a handful of medications
00:08:26
that are called monoclonal antibodies
00:08:30
these are antibodies that can get into
00:08:32
the brain bind to the buildup of the
00:08:34
amyloid protein and help the brain's
00:08:37
immune system remove that amyloid
00:08:39
protein from the brain and so all of
00:08:42
these they have some unusual names but
00:08:44
they end in m a b which stands for
00:08:47
monoclonal antibody so any drug that
00:08:49
ends in mab is an antibody not all mab
00:08:52
medications are anti-amyloid antibodies
00:08:55
but this slide shows the family of
00:08:59
amyloid antibodies that have been used
00:09:01
recently in clinical trials and this
00:09:04
just shows how the amyloid protein in
00:09:07
the setting of Alzheimer's disease it's
00:09:09
starts to form first smaller and then
00:09:12
larger clumps that eventually turn into
00:09:15
these more dense plaques that build up
00:09:17
in the brain and depending on the
00:09:19
specific antibody some of these
00:09:21
antibodies are geared to bind to the
00:09:23
more initial clumping stages some are
00:09:26
geared to design to the more dense
00:09:28
plaque aggregations that occur in the
00:09:30
brain it's not clear yet whether it
00:09:32
matters what stage the the antibody
00:09:34
binds to but there may be some reasons
00:09:36
that that could be important but all of
00:09:38
these have been studied as potential
00:09:40
therapies for Alzheimer's disease in
00:09:43
people with symptoms
00:09:45
and as you may know one of them called
00:09:49
adducanumab was approved as a treatment
00:09:52
for Alzheimer's disease in the early
00:09:54
symptomatic stages was approved by the
00:09:57
FDA back in June of 2021 and as you can
00:10:01
see from this picture it's different
00:10:03
from all the medications we were
00:10:04
previously using that were pills this is
00:10:07
an intravenous medication because the
00:10:10
antibody doesn't come in a pilliform and
00:10:12
can't get into the brain in a pill form
00:10:14
so it's delivered intravenously gets
00:10:16
into the brain binds to the amyloid
00:10:18
plaque to help it remove it so what do
00:10:21
we know about educanuman the drug that
00:10:23
was approved back in 2021
00:10:26
well in its initial phase trials they
00:10:29
looked specifically to see does this
00:10:32
drug help do what we think it can do and
00:10:35
that is remove amyloid buildup from the
00:10:37
brain and so this slide shows the
00:10:39
results of one of the early phase Trials
00:10:41
of educanumab in this case all the
00:10:44
individuals had the condition of
00:10:45
interest because they were looking to
00:10:47
see can it remove amyloid so you had to
00:10:49
know that individuals had amyloid in the
00:10:51
brain so this study was done in about
00:10:54
165 individuals with either very early
00:10:58
symptoms at the mild cotton impairment
00:11:00
stage or mild dementia due to
00:11:02
Alzheimer's disease and all the
00:11:04
individuals underwent specialized brain
00:11:07
scans that showed they had buildup of
00:11:09
the amyloid fat protein so the left hand
00:11:12
column here these are just some of the
00:11:15
specific amyloid pet scans before the
00:11:17
start of the study they use a tracer
00:11:20
that gets into the brain and if there is
00:11:21
amyloid buildup there the Tracer will
00:11:24
bind and the visual signal of that is
00:11:26
this red bright red coloration that
00:11:29
indicates the Tracer is fine so all
00:11:31
these individuals had evidence of
00:11:33
amyloid buildup in the brain at the
00:11:34
start of the study and they were
00:11:36
randomly assigned to receive regular
00:11:39
infusions of educanumab essentially on a
00:11:43
monthly basis for a year and they could
00:11:45
receive either the placebo or one of
00:11:48
three different doses
00:11:50
and they look to see at the end of the
00:11:52
year what did the pet scans look like
00:11:54
and the individuals who received the
00:11:56
placebo essentially showed a similar
00:11:58
degree if not perhaps slightly higher
00:12:00
amount of amyloid buildup in the brain
00:12:02
whereas the individuals receiving the
00:12:04
active drug you could see a
00:12:06
dose-dependent removal of the amyloid so
00:12:09
the individuals receiving the highest
00:12:10
dose had what essentially looked like a
00:12:13
normal pet scan there really wasn't
00:12:15
detectable binding of the Tracer so it
00:12:17
was clear that this drug could do what
00:12:19
it was intended to do get into the brain
00:12:22
and help remove the amyloid however in
00:12:26
addition to seeing a dose-dependent
00:12:28
benefit or effect in terms of removing
00:12:31
the amyloid from the brain there were
00:12:33
dose-dependent side effects and those
00:12:36
were often picked up on standard MRI
00:12:39
scans where at higher doses in
00:12:42
particular some individuals developed
00:12:45
either small amounts of swelling as sort
00:12:47
of fluid was shifting into the brain or
00:12:50
tiny areas of bleeding what are called
00:12:51
micro hemorrhages and those were
00:12:54
detected more commonly among individuals
00:12:56
who received the higher dose of the drug
00:12:58
so the question has been is the benefit
00:13:02
of removing the plaque is it more
00:13:05
important than the potential side effect
00:13:06
of this bleeding or swelling a lot of
00:13:09
times that bleeding or swelling was
00:13:11
clinically silent the people who had
00:13:13
those radiologic changes didn't have any
00:13:15
symptoms but in some cases they did as a
00:13:19
group those radiologic changes are
00:13:20
called Aria stands for amyloid related
00:13:23
Imaging abnormality because again
00:13:25
they're often detected on Imaging scans
00:13:28
on brain scans even if the individual
00:13:30
isn't experiencing symptoms
00:13:33
um so the big question was is removing
00:13:35
the amyloid actually beneficial to the
00:13:37
individual or does it just make a pet
00:13:39
scan look better after a year of therapy
00:13:42
so as you can I'm actually skipped sort
00:13:46
of the phase two and went directly into
00:13:48
two large phase three studies
00:13:50
specifically designed to try to answer
00:13:52
the question what is the benefit of
00:13:55
receiving this drug removing the amyloid
00:13:57
from the brain and again what are the
00:13:59
potential risks in terms of the Aria or
00:14:01
any other types of side effects so two
00:14:04
large studies were designed to answer
00:14:06
that specific question
00:14:07
together they enrolled more than 3 000
00:14:10
individuals again these individuals all
00:14:13
had early symptoms of Alzheimer's either
00:14:15
in the mild dementia stage or in the
00:14:18
mild cognitive impairment stage and they
00:14:20
all had evidence of brain amyloid
00:14:22
buildup by undergoing studies such as
00:14:24
those amyloid pet scans and they were
00:14:27
randomly assigned to receive either
00:14:29
Placebo a low dose or a higher dose and
00:14:32
the intention was to follow everyone
00:14:34
over a year and a half to see if there
00:14:38
was a difference in terms of the
00:14:40
Dementia or mild counter impairment a
00:14:42
difference in their cognitive symptoms
00:14:43
over that time frame depending on
00:14:46
whether they got the active drug versus
00:14:48
the placebo
00:14:50
and the main thing that they looked at
00:14:52
to determine whether the drug was having
00:14:55
an effect was a rating of someone's
00:14:58
cognitive impairment and this rating is
00:15:01
something called the clinical dementia
00:15:03
rating scale it's not something that's
00:15:05
typically done in the setting of a
00:15:07
standard Clinic visit when someone's
00:15:09
being followed for Alzheimer's disease
00:15:11
dementia this is a more lengthy
00:15:14
interview both with the person
00:15:16
experiencing the symptoms and someone
00:15:18
who knows them well a close friend or
00:15:20
family member and the interview asks
00:15:22
questions about how are their how
00:15:24
they're doing in terms of tests that
00:15:26
involve memory do they seem to know in
00:15:29
general the day and date and where
00:15:30
they're at or not how do they do out and
00:15:33
about in the community are they able to
00:15:35
function independently go run errands
00:15:36
things like that or do they need regular
00:15:39
assistance and how do they do in the
00:15:40
home environment in terms of their
00:15:42
household activities or hobbies and what
00:15:45
about their personal care and so both
00:15:47
someone who knows the individual well
00:15:49
and the individual dual him or herself
00:15:51
are interviewed and tested as part of
00:15:53
that interview and in the end the Raider
00:15:56
makes a decision about whether they are
00:15:59
seeing impairments in one of six
00:16:01
different areas and how much of an
00:16:03
impairment they are seeing so if this
00:16:04
individual is felt to be functioning
00:16:06
perfectly normal Lee they would get a
00:16:08
rating of zero in each of their areas
00:16:10
their memory isn't changing they're well
00:16:12
oriented they know where they are they
00:16:14
know that the time of day their judgment
00:16:17
seems intact they can function
00:16:19
independently in the community at home
00:16:21
and in their personal care they get a
00:16:23
rating of 0.5 that suggests there's been
00:16:25
a mild change maybe they don't forget
00:16:28
things entirely but some of the details
00:16:30
whereas if they're rated a one recent
00:16:33
events are really slipping from their
00:16:34
memory they might not remember them at
00:16:36
all for example for orientation maybe
00:16:38
they're off on the day or date
00:16:40
frequently but if they're rated a one
00:16:43
they may not know the month or the year
00:16:45
but they may still not know where they
00:16:47
are if they are confused about their
00:16:49
location they might marry a higher level
00:16:51
of impairment so in the end each of
00:16:53
these areas is rated
00:16:55
and you can either create a global score
00:16:58
by in the sense averaging them or you
00:17:00
can just sum up their total score and
00:17:02
see how what's their total score a
00:17:05
higher score would be more impairment so
00:17:08
individuals who are maybe still function
00:17:10
independently but not quite at the level
00:17:12
they were before they may get a lot of
00:17:14
0.5s individuals who are starting to
00:17:16
need assistance may get a lot of ones
00:17:18
and then you just track these scores
00:17:20
over time to see how they do and compare
00:17:23
this in the treatment group in the
00:17:25
placebo group
00:17:26
well it gets a little more complicated
00:17:28
because in the end these large phase
00:17:30
three studies were halted before their
00:17:34
intended completion date because they
00:17:36
did an interim analysis that predicted
00:17:38
the drug would not show a benefit in the
00:17:41
two studies combined but when they
00:17:43
looked at the data after they had halted
00:17:45
it so not everyone had made it through
00:17:47
to the 18-month time point but they
00:17:49
looked at the data that they'd
00:17:51
accumulated and lo and behold the two
00:17:53
studies ended up giving somewhat
00:17:55
different results so in the emerge study
00:17:58
if you tracked that score on the
00:18:00
clinical dementia rating scale and in
00:18:03
this graph a higher score is higher up
00:18:06
on the y-axis so as this as these uh
00:18:10
as these lines are increasing that means
00:18:13
a higher CDR score which means more
00:18:16
impairment so in the emerge study a
00:18:19
higher dose group didn't have as much of
00:18:22
an increase in their CDR score as the
00:18:25
placebo so there was a difference of
00:18:27
about 0.39 which is about the difference
00:18:31
between one box here and here so not
00:18:35
quite a full half point but it means
00:18:36
that an individual might have stayed in
00:18:39
this box instead of Shifting to this box
00:18:41
over the course of the study if they
00:18:42
receive treatment but all other boxes
00:18:45
change the same way
00:18:47
another way of looking at it is that the
00:18:50
high-dose treatment group was
00:18:52
functioning at a level that the placebo
00:18:55
group was functioning at maybe four to
00:18:58
five months earlier so it's as though
00:18:59
it's slowed that decline by four to five
00:19:01
months over the 18 months of the study
00:19:04
so it's suggested a benefit in slowing
00:19:06
down the progression of the symptoms in
00:19:09
one study but in the other study study
00:19:11
there wasn't a detectable difference so
00:19:13
the cdrs the scores people were
00:19:16
progressing gradually declining whether
00:19:18
they got the high dose or the placebo
00:19:19
and so the question was what what does
00:19:22
this mean it does the drug maybe work
00:19:24
sometimes work there are a lot of
00:19:26
technical reasons why these different
00:19:28
results may have occurred but ultimately
00:19:30
we don't know well you might say gosh
00:19:32
even if we don't know if it's clearly
00:19:34
helpful even if there's a chance it
00:19:36
slows things down is it it might be
00:19:38
worth it for a disease that we know
00:19:39
progresses without therapy but we have
00:19:42
to balance that with the side effects
00:19:43
and as I mentioned before with the
00:19:46
monoclonal antibodies we know when they
00:19:47
get into the brain and bind there can be
00:19:50
some Associated swelling of the brain
00:19:52
tissue or bleeding and in this case with
00:19:54
educanumab on the high dose
00:19:58
40 percent of individuals had at least
00:20:00
radiologic evidence of either the
00:20:03
swelling the edema or the Hemorrhage or
00:20:06
some combination thereof most of the
00:20:09
time it didn't cause symptoms but about
00:20:11
a quarter of those who had detectable
00:20:13
changes on the scans did experience
00:20:15
symptoms that kind of correlated with
00:20:17
either where that swelling was so if the
00:20:19
swine was in the back of the brain they
00:20:21
might experience some visual changes
00:20:23
because that's where our brain processes
00:20:24
visual information or just from the
00:20:26
swelling no matter where it occurred
00:20:28
they might develop a headache or nausea
00:20:30
or things like that so
00:20:32
um in in these individuals often the
00:20:34
dose had to be stopped and they had to
00:20:36
be monitored to see if those symptoms
00:20:37
recovered
00:20:39
so what do you do with information that
00:20:41
says the drug may or may not have a
00:20:43
benefit but it does have some known side
00:20:45
effects well what the FDA did was they
00:20:49
granted approval but through a mechanism
00:20:51
that's a little different than the
00:20:53
traditional approval they granted what's
00:20:55
called accelerated approval which is a
00:20:58
conditional type of approval that's
00:21:00
based on a Drug's biological effect and
00:21:03
I think it's very clear this drug has a
00:21:05
biological effect it can remove the
00:21:07
amyloid buildup from the brain
00:21:09
but with an accelerated approval that
00:21:12
biological effect is hoped to be
00:21:15
translated into a clinical effect but
00:21:17
that doesn't have to be established yet
00:21:19
so when accelerator approval is granted
00:21:21
there is typically a requirement to have
00:21:23
an additional study to confirm does that
00:21:26
biological effect really translate into
00:21:28
a clinical benefit or not and so there
00:21:31
is an additional trial underway to try
00:21:33
to see ultimately does this drug have a
00:21:36
clinical benefit but given that it's
00:21:39
only a conditional approval Medicare
00:21:41
last year decided that it would not
00:21:44
cover it except in the context of a
00:21:46
clinical trial to really help understand
00:21:48
does this drug have benefits that
00:21:50
outweigh the risk which means for all
00:21:52
practical purposes we aren't prescribing
00:21:55
this medication because it's not covered
00:21:57
by insurers so it's really only
00:21:59
continuing on in clinical trials and in
00:22:02
fact many institutions individually
00:22:04
reviewed the risk and benefit
00:22:06
information and decided there wasn't
00:22:07
enough benefit to outweigh that risk to
00:22:10
offer it and so again its use is really
00:22:13
restricted at this point to to clinical
00:22:15
trials but again it is approved by the
00:22:18
FDA for individuals at an early
00:22:20
symptomatic stage of Alzheimer's either
00:22:22
mild cutter impairment or mild dementia
00:22:24
but it needs to be given very carefully
00:22:27
for example individuals need to be able
00:22:29
to be followed with the MRI scans to
00:22:32
look for some of these radiologic
00:22:34
findings to be able to adjust the dose
00:22:36
or halt the dose if that's appropriate
00:22:38
to do so
00:22:39
so that's kind of where we stood last
00:22:41
year but what's been the more recent
00:22:44
development well now if you've been
00:22:45
hearing the news you've heard about a
00:22:47
drug called luck in a lab rather than
00:22:49
adjectana map and somebody might say
00:22:51
well la Cana map is it just the French
00:22:53
version of edge Academy no it's it's a
00:22:55
different drug but it's the same idea
00:22:57
it's another monoclonal antibody and
00:23:00
just as with that you canimab it did an
00:23:03
early study to look to see what is the
00:23:06
effect of this drug on the amyloid
00:23:08
buildup in the brain and so in this
00:23:10
study individuals had amyloid cut scans
00:23:13
were assigned to different doses of the
00:23:15
drug and lo and behold they also showed
00:23:18
a dose-dependent removal of the amyloid
00:23:21
plaque so they didn't publish nice
00:23:22
pictures the way they educator map study
00:23:24
did but they published their graph
00:23:26
showing the drop in the amyloid buildup
00:23:28
that was most impressive with the
00:23:31
highest most frequent dose and less
00:23:33
impressive with lower or less frequent
00:23:36
dosing and So based on this biological
00:23:40
effect the FDA just just granted Latina
00:23:44
map that same accelerated or conditional
00:23:47
approval that educantum have received
00:23:49
previously so this again has been
00:23:52
approved by the FDA because it has a
00:23:55
biological effect in a disease that
00:23:56
doesn't have good therapies at this time
00:23:59
so the hope is further studies would be
00:24:01
able to be done to show that not only
00:24:03
does it reduce the amyloid but it has a
00:24:05
clinical benefit well in fact one of
00:24:07
those studies has already been done just
00:24:10
not reviewed yet by the FDA but the
00:24:13
results of it were just announced in the
00:24:15
last few months this was a phase three
00:24:18
trial called Clarity and as the name
00:24:21
implies it was designed to give Clarity
00:24:23
does this drug have a clinical benefit
00:24:26
not just a benefit in terms of changing
00:24:29
a pet scan and so this phase three Taro
00:24:32
nearly 1800 individuals all again in an
00:24:36
early symptomatic stage of Alzheimer's
00:24:38
disease they were followed over time and
00:24:41
compared with that same clinical
00:24:43
dementia rating scale outcome measure
00:24:45
now for their publication they flipped
00:24:47
it so that as the CDR score is
00:24:51
increasing you actually fall further
00:24:53
down on this graph and so falling down
00:24:56
means that the dementia is worsening or
00:24:59
the cognitive impairment is worsening
00:25:00
but you see a difference between the
00:25:03
group who received the placebo their
00:25:06
decline was greater at the end of 18
00:25:08
months compared to the group receiving
00:25:10
the lakina map and that absolute
00:25:13
difference on that CDR scale was about
00:25:16
0.45 so again sort of one box different
00:25:20
on the left hand side of the scale but
00:25:23
that did represent a 27 percent slowing
00:25:26
of that rate of decline one thing that
00:25:29
looks even more promising is that these
00:25:33
curves or these lines seem to be
00:25:35
separating more as time goes on so it's
00:25:39
possible if the trial had continued more
00:25:41
than 18 months you might see an even
00:25:44
greater separation between the treatment
00:25:45
group and the placebo group we don't
00:25:47
know that because the trial did end at
00:25:49
18 months but at this point we can say
00:25:52
if an individual had been coming in and
00:25:54
getting infusions of lacanumab in this
00:25:56
case they are infusions every two weeks
00:25:58
rather than the monthly infusions with
00:26:00
Edge Academy but at the end of those 18
00:26:03
months of infusions they would be
00:26:05
functioning roughly where the placebo
00:26:07
group was functioning at about 12 months
00:26:11
so it appears to sort of again slow that
00:26:13
decline by about six months over the one
00:26:17
and a half years or 18 months of the
00:26:19
trial so you could look at it saying if
00:26:21
someone was doing something
00:26:22
independently if they received a
00:26:24
treatment they may be able to keep doing
00:26:26
that for six months longer than someone
00:26:28
who only received the placebo
00:26:30
what's the downside again was there any
00:26:33
evidence of Arya yes
00:26:35
um swelling and small bleeding did occur
00:26:37
the rate was lower than in the
00:26:40
educanumab trial so it was about 22
00:26:42
percent and in in most cases again it
00:26:45
was clinically silent it didn't change
00:26:47
people's day-to-day function or cause
00:26:49
any symptoms but at a small percent
00:26:51
um there were symptoms and this data
00:26:54
will all be reviewed by the FDA to
00:26:56
determine whether to Grant the drug full
00:26:58
approval or not and we'll have to wait
00:27:00
and see do insurers like Medicare will
00:27:04
they continue to approve it only in the
00:27:08
context of clinical trials or will they
00:27:10
say yes we'll approve it for regular use
00:27:12
if the FDA grants a full approval or if
00:27:15
um if they review this information as
00:27:17
well
00:27:19
um they did look at other outcome
00:27:20
measures too besides that clinical
00:27:22
dementia rating scale if you looked at
00:27:24
the pet scans again a dramatic dropping
00:27:26
of the amyloid on the treatment group
00:27:28
compared to the placebo if you looked at
00:27:30
other clinical measures these are either
00:27:31
tests of thinking or measurements of
00:27:34
day-to-day activities all of them showed
00:27:36
less decline in the treatment group
00:27:38
compared to the placebo so really
00:27:41
consistent evidence that there is a
00:27:43
difference between like anime and
00:27:44
Placebo unfortunately it's not a major
00:27:47
difference it's more modest but it does
00:27:49
appear to slow that progression again we
00:27:52
need to balance that out against the
00:27:54
potential side effects which were not
00:27:56
equally experienced among all members of
00:27:59
the trials it turns out that those
00:28:02
individuals who carry a specific genetic
00:28:04
risk factor or Alzheimer's disease
00:28:07
called the APO lipoprotein E4 genotype
00:28:11
those individuals particularly if they
00:28:13
have two copies if both of their apoe
00:28:15
genes are the type 4 they had a much
00:28:18
greater likelihood of experience the
00:28:20
Aria types of side effects so if they
00:28:23
divided the likelihood of detecting
00:28:25
swelling on an MRI scan if you didn't
00:28:27
have any copies of the apoe4 it was only
00:28:30
five percent compared to if you had two
00:28:32
copies it was up at 30 percent and ten
00:28:36
percent of the time that almost 10
00:28:37
percent of the time that led to symptoms
00:28:39
so this has really led to the thought
00:28:42
that if we do offer this medication we
00:28:45
will really want to know who genetically
00:28:47
is going to be at a higher risk of some
00:28:50
of these side effects because that may
00:28:51
change ultimately the decision about
00:28:53
whether to pursue this type of treatment
00:28:57
but in the end we say gosh is this going
00:28:59
to be a practical way of treating most
00:29:02
individuals with early Alzheimer's
00:29:04
symptoms coming in every two weeks for
00:29:05
infusions that's a that's a lot of time
00:29:10
and Logistics are there other ways of
00:29:13
making these types of therapies more
00:29:15
realistic to be used on the numbers of
00:29:17
individuals experiencing this condition
00:29:19
well one of the other antibodies
00:29:21
antenerimab was studied in a
00:29:24
subcutaneous form so just small needle
00:29:27
injections under the skin that could be
00:29:28
given at home and potentially even be
00:29:30
you know administered by someone in the
00:29:32
home rather than needing to come into
00:29:33
infusion center so there was promising
00:29:36
hope for this as a more straightforward
00:29:38
or a logistically more feasible way of
00:29:41
treating individuals but unfortunately
00:29:42
in its large phase three studies they
00:29:45
didn't show any significant slowing of
00:29:47
Decline and it turns out that the
00:29:49
amyloid removal when they measured it
00:29:51
was lower than the expected suggesting
00:29:54
this drug just may not have been
00:29:55
powerful enough to either see the a
00:29:57
benefit in amyloid removal or a clinical
00:29:59
benefit so it really hasn't been seen as
00:30:03
an option
00:30:04
there's another drug that the FDA
00:30:08
reviewed just last week it's another
00:30:11
monoclonal antibody called dinanumab and
00:30:14
it looks like it can remove plaque very
00:30:17
quickly they actually interestingly did
00:30:20
just a pet only study looking at pet
00:30:23
scans before and after six months of
00:30:25
treatment with their drug donatumab and
00:30:28
that previous drug that I mentioned
00:30:29
educanumab and we're able to show that
00:30:31
in six months there was much more plaque
00:30:34
removal with danina map compared to
00:30:35
educanuman well why is this important
00:30:38
well one thought was maybe you don't
00:30:39
have to treat someone with this drug as
00:30:42
long as you might have to with some of
00:30:44
the others maybe you can remove that
00:30:45
plaque rapidly and don't have to keep
00:30:47
dosing once that plaque is gone so it
00:30:50
may not be 18 months of therapy maybe
00:30:51
it's only 6 or 12 months of therapy and
00:30:54
then you can stop dosing when the plaque
00:30:56
is gone we don't know yet whether that
00:30:58
will truly have a clinical benefit
00:31:00
because those trials are ongoing but
00:31:02
this was submitted for the FDA to review
00:31:04
you to see if they would Granite
00:31:06
accelerator approval again accelerate
00:31:08
approval saying does this drug have a
00:31:10
promising biological effect in terms of
00:31:12
amyloid removal and interestingly the
00:31:15
FDA decided not to Grant approval not
00:31:17
because they weren't convinced I think
00:31:19
by this type of data or other data were
00:31:21
submitted but they said gosh there
00:31:23
haven't been enough people on the drug
00:31:24
for long enough periods of time very few
00:31:27
people have been on this drug for a year
00:31:28
for example and in some cases you might
00:31:31
need to give it for a year to fully
00:31:32
remove that AMOLED plaque but in some
00:31:34
ways because the plaque has been removed
00:31:36
so quickly they didn't have enough
00:31:38
people on the drug for a year for the
00:31:40
FDA to say we've seen enough safety data
00:31:43
about it to feel comfortable approving
00:31:45
it so the FDA declined to granted
00:31:47
accelerated approval but these phase
00:31:50
three trials looking at not just plaque
00:31:52
removal but clinical benefit as well are
00:31:55
expected to release their results later
00:31:57
on this year and so the FDA will then
00:31:59
likely review it to determine if it
00:32:01
should receive traditional approval so
00:32:03
we might have yet enough other potential
00:32:05
therapy in terms of a monoclonal
00:32:07
antibody again some benefits slowing the
00:32:10
disease we hope but some risk as well so
00:32:12
these need to be balanced very carefully
00:32:15
so in the end you say well gosh if we
00:32:18
can get rid of amyloid from the brain
00:32:19
and we know that's one of the Hallmarks
00:32:21
of Alzheimer's why aren't we getting a
00:32:23
more dramatic effect why aren't we
00:32:24
really halting the disease or reversing
00:32:26
the disease and the answer is we don't
00:32:28
know but one possible reason is by the
00:32:31
time we're giving these drugs to people
00:32:33
with symptoms of either mild Dementia or
00:32:36
mild kind of impairment the amyloid
00:32:39
plaque has really been building up for
00:32:41
many years in a silent phase so that
00:32:44
amyloid pathology begins before the
00:32:46
symptoms are ever apparent so by the
00:32:48
time we're treating individuals who have
00:32:50
symptoms we're trying to address a
00:32:52
problem that's been changing in the
00:32:54
brain for several years so maybe it just
00:32:56
isn't isn't going to be enough once
00:32:58
people have developed the symptoms of
00:33:00
Alzheimer's disease but potentially
00:33:03
maybe there would be a greater benefit
00:33:05
maybe you could forestall symptoms not
00:33:07
just for six months but maybe for years
00:33:09
or more if you delivered these
00:33:12
treatments as people were starting to
00:33:14
develop the plaque rather than many
00:33:15
years years later so that in fact is the
00:33:18
question that's been posed to a lot of
00:33:20
prevention trials using the same
00:33:22
monoclonal antibody agents so many of
00:33:26
the ones that I just mentioned have
00:33:27
either been studied in trials in
00:33:30
individuals at risk for Alzheimer's one
00:33:33
of them unfortunately didn't show a
00:33:34
benefit but the dosing was felt to
00:33:36
probably too low at the time
00:33:39
when the get to narimab data that I
00:33:41
presented earlier when it didn't show a
00:33:44
clinical benefit the company decided to
00:33:46
sort of stop development so there isn't
00:33:47
going to be a prevention trial with it
00:33:49
but both like canimab and denatumab have
00:33:53
trials in individuals at risk for
00:33:55
Alzheimer's to see if giving infusions
00:33:58
early on can prevent the risk of those
00:34:01
symptoms emerging and there's a trial
00:34:04
that has been going on for several years
00:34:05
using another monoclonal antibody called
00:34:08
solanasumab and we expect to hear the
00:34:11
results of that trial later on this year
00:34:13
so so stay tuned and I will just mention
00:34:16
that we are currently participating in
00:34:19
this so we hope to hear the results
00:34:20
release those results in the next
00:34:23
several months and we're currently at
00:34:25
the University of Michigan recruiting
00:34:26
individuals to participate in the
00:34:28
lakinumab prevention trial it's called
00:34:31
the ahead study and it's looking for
00:34:33
individuals who may be at risk for
00:34:35
developing Alzheimer's symptoms later in
00:34:37
life partly just because there are aging
00:34:40
we know that's a number one risk but
00:34:42
also maybe if you're younger but have a
00:34:44
strong family history or you know you
00:34:46
carry one of those genetic risk factors
00:34:48
like the April lipoprotein E4 Gene that
00:34:51
would enable you to be screened for this
00:34:53
study ultimately individuals in this
00:34:56
trial will undergo those amyloid pet
00:34:59
scans to see if they have amyloids
00:35:01
silently building up and depending on
00:35:04
the level of that buildup they'll
00:35:06
receive the active drug or Placebo
00:35:08
either on a essentially a monthly basis
00:35:11
or every two weeks so pitching the more
00:35:13
frequent infusions to individuals who
00:35:15
have a higher level of amyloid buildup
00:35:17
and the less frequent infusions to those
00:35:19
who have a more intermediate level of
00:35:20
buildup
00:35:22
um but this trial is also unique but
00:35:24
besides just being a prevention trial
00:35:25
it's actually doing a pre-screening
00:35:27
stage before people get to the amyloid
00:35:30
pet scan stage by looking at blood
00:35:33
levels of amyloid because it turns out
00:35:35
you can measure very very tiny
00:35:37
quantities of amyloid in the blood that
00:35:40
can give you a reasonable indication
00:35:41
about whether amyloid may be building up
00:35:44
in the brain now these tests aren't
00:35:45
perfect yet and so they're just being
00:35:47
used as an initial screen to say is
00:35:50
there some chance we might find amyloid
00:35:52
in the brain based on this Blood result
00:35:54
and if so those individuals can move
00:35:56
forward to have the Pet Scan and we know
00:35:58
in many cases the Pet Scan may not show
00:36:00
any buildup so the blood biomarkers
00:36:02
aren't being used as a substitute but
00:36:04
just as a way to take an initial look
00:36:06
and see can we refine who needs to have
00:36:09
the Pet Scan based on a blood prediction
00:36:12
about amyloid buildup and so individuals
00:36:15
in the study will have regular pet scans
00:36:17
regular MRI scans for safety reasons and
00:36:20
tracking to see how their cognition does
00:36:23
over time they're all starting with
00:36:25
normal thinking abilities and we want to
00:36:26
know does treatment change the course
00:36:29
over the next several years in terms of
00:36:30
whether they develop cognitive symptoms
00:36:32
or other types of changes
00:36:36
so let me spend a little time now
00:36:37
Switching gears away from amyloid again
00:36:40
that's where all the big news has been
00:36:42
lately but just at least mention some of
00:36:44
the other types of studies that are out
00:36:46
there in Alzheimer's disease clinical
00:36:48
trials some of them have focused on the
00:36:51
other main pathology and Alzheimer's
00:36:53
disease the Tau protein that builds up
00:36:56
in the form of the tangles inside the
00:36:59
nerve cell compared to the plaques that
00:37:01
are building up outside the nerve cell
00:37:02
so why might that be an important Target
00:37:05
well it turns out that the Tau pathology
00:37:08
actually correlates better with the loss
00:37:11
of nerve cells and the clinical symptoms
00:37:13
compared to the amyloid pathology as you
00:37:16
could imagine from what I've already
00:37:18
said people can have a lot of amyloid in
00:37:20
their brain and it can be completely
00:37:21
silent that's why they're being enrolled
00:37:23
in prevention trials because they aren't
00:37:25
having symptoms but we're trying to
00:37:26
prevent those symptoms but when towels
00:37:29
start spreading their brain that's when
00:37:30
symptoms really start to develop and so
00:37:32
perhaps targeting the town might help
00:37:35
people who are already exhibiting the
00:37:38
symptoms it may be more effective than
00:37:40
targeting the amyloid maybe the amyloid
00:37:42
treatments need to be earlier but the
00:37:43
Tau treatments could still be given
00:37:45
later and in fact it turns out in at
00:37:48
least animal studies you can have a lot
00:37:49
of amyloid in your brain but if you
00:37:51
control the Tau you might be able to
00:37:53
prevent or modify those cognitive
00:37:55
deficits so that was the conclusion of
00:37:58
this study from years ago where
00:38:00
essentially laboratory mice who are
00:38:04
genetically engineered to develop a form
00:38:06
of Alzheimer's they could manipulate
00:38:08
whether amyloid or Tau became expressed
00:38:11
in their brain and they looked to see
00:38:13
could a mouse learn the position of a
00:38:16
submerged platform in kind of a Milky
00:38:18
pool of water because the mice didn't
00:38:20
like swimming around constantly they
00:38:21
want to find that platform in rest and
00:38:23
so they put them in this container which
00:38:27
has some
00:38:28
basically has some landmarks they can
00:38:30
look around and sort of decide where
00:38:32
they are and once they learn where that
00:38:33
submerged platform is the next time they
00:38:35
put them in the container they look at
00:38:37
the landmarks and say aha I know where
00:38:39
to go to find that platform if they can
00:38:40
remember it so a normal Mouse after
00:38:44
they've learned it is you know pretty
00:38:45
much spending its time right where the
00:38:46
platform is but a mouse that has a lot
00:38:49
of amyloid and talent its brain is
00:38:51
really randomly swimming around the
00:38:53
different quadrants can't find that
00:38:54
submerged platform but a mouse that's
00:38:57
not allowed to develop the town buildup
00:38:59
that can develop the amyloid build up
00:39:01
still can learn where that submerged
00:39:03
platform is so again the Tau May
00:39:06
correlate better with the cognition so
00:39:07
Tau therapies may help people once
00:39:10
symptoms have already been present
00:39:12
so where do we stand in town therapies
00:39:15
for Alzheimer's disease well just like
00:39:17
there are amyloid antibodies there are
00:39:19
also Tau antibodies under development
00:39:21
for Alzheimer's disease unfortunately
00:39:24
the studies so far have not shown great
00:39:26
promise as they've moved along from
00:39:29
phase one to phase two for example so
00:39:31
many of the ones that have been studied
00:39:33
so far have not shown a clear clinical
00:39:36
benefit
00:39:37
One Drug showed a slight difference at
00:39:40
the very end of the study on one measure
00:39:42
but not on any of the other measures of
00:39:44
cognition and the thought might be that
00:39:47
not all Tau antibodies are equally
00:39:50
effective it may depend on what part of
00:39:52
the tile protein the antibody is
00:39:54
targeting so other antibodies aimed at
00:39:57
different sections of the Tau protein or
00:39:59
other immune approaches vaccines that
00:40:01
allow you to develop your own Tau
00:40:03
antibodies those are now moving forward
00:40:05
in clinical trials so we'll have to stay
00:40:07
tuned to see if those are potentially
00:40:09
more effective and there have been a lot
00:40:11
of other agents trying to block just the
00:40:14
buildup of the towel itself not by an
00:40:17
antibody to remove it by but just
00:40:19
preventing the towel from accumulating
00:40:21
the form of Tangles
00:40:22
um so there's a company that in fact is
00:40:24
so dedicated to
00:40:26
um towel therapy specifically it's
00:40:28
called Tau RX so they're really looking
00:40:30
at therapies for Alzheimer's that Target
00:40:32
Tau and they've looked at compounds that
00:40:35
again are thought to be able to prevent
00:40:37
the accumulation of the Tau in the form
00:40:39
of the tangles
00:40:41
and the most recent compound they
00:40:43
studied it goes by name that is too long
00:40:45
to pronounce so it's abbreviated hmtm
00:40:48
but it's an oral compound so it doesn't
00:40:50
have to be given intravenously it's
00:40:52
chemically related to a dye called
00:40:54
methylene blue
00:40:56
so one of its interesting side effects
00:40:59
is that someone takes it my mouth it
00:41:01
will turn body fluid specifically urine
00:41:04
will turn blue and so it makes it very
00:41:06
easy to know if you're taking the active
00:41:08
drug compared to a placebo which is
00:41:10
always made it a challenge if you want
00:41:12
to do comparative studies so in their
00:41:15
phase three trial called Lucidity they
00:41:17
gave individuals either the hmtm or a
00:41:21
related compound that was meant to
00:41:23
function as a placebo but had still that
00:41:26
blue chemical effect so people couldn't
00:41:28
tell whether they were getting the
00:41:29
active drug or the placebo just by that
00:41:31
blue coloration and so in the end when
00:41:34
they compared how cognition changed in
00:41:37
individuals with different levels of
00:41:39
cognitive impairment from Alzheimer's
00:41:40
they didn't see a difference between
00:41:42
those taking the hmtm and those taking
00:41:45
the MTC but as it turned out when they
00:41:49
started measuring blood levels of what
00:41:51
they thought was the active component
00:41:53
they could detect it both in those who
00:41:55
receive the h MTM and in those who
00:41:58
receive what they thought was the
00:42:00
placebo so maybe it wasn't that the drug
00:42:03
didn't work it's just that both worked
00:42:05
and so you couldn't tell the difference
00:42:07
so this is going to need some further
00:42:09
thought to tease that out because it's
00:42:10
really hard to make a comparison if both
00:42:13
people are getting sort of active
00:42:14
treatments during this study
00:42:17
um so I think is still a viable approach
00:42:19
we just need more information and more
00:42:21
compounds but there have been some
00:42:23
really interesting studies presented
00:42:25
recently not clinical trials in humans
00:42:27
but some research researchers are
00:42:30
focusing on Tau changes in animals it
00:42:33
was known from previous studies that Tau
00:42:35
can accumulate in the brain of
00:42:37
hibernating animals in a way that's
00:42:40
similar to how the Tau Tangles build up
00:42:42
in humans when they experience
00:42:44
Alzheimer's disease they get these
00:42:46
tangle-like structures this was known
00:42:48
from I think hibernating squirrels that
00:42:50
they studied in the lab or other animal
00:42:51
species but someone got the idea to look
00:42:54
at this in hibernating bears and so some
00:42:57
researchers actually went out and
00:42:58
collected blood samples from bears
00:43:00
during their hibernation and later on in
00:43:03
the summer when they woke back up these
00:43:05
were measurements of towel in the blood
00:43:06
again I mentioned we can now measure
00:43:09
these proteins in the blood and get
00:43:10
predictions about what's going on in the
00:43:12
brain and it turns out they did have
00:43:14
more of the tangle like how in their
00:43:17
bloodstream when they were hibernated
00:43:19
but those levels fell back to normal
00:43:21
during the summer very interesting
00:43:23
observation we don't know what it means
00:43:25
we don't know if that tau is protecting
00:43:29
the brain while the animal is in
00:43:30
hibernation is it is it a good response
00:43:33
or is it a not great response but the
00:43:35
good part is when the animal wakes up
00:43:37
from hibernation it clears it and what's
00:43:38
the secret of clearing that can we study
00:43:41
that as a way of potentially clearing
00:43:43
Tau buildup in humans so you know can we
00:43:45
figure out what that process is and I
00:43:47
think the other interesting question was
00:43:48
who is heroic enough to draw blood from
00:43:52
hibernating bears and awaken them from
00:43:54
their sleep to be able to collect these
00:43:57
samples so a lot more to be learned I'm
00:44:00
going to switch gears in the final few
00:44:02
minutes and talk about some studies that
00:44:04
don't have anything to do or at least
00:44:05
not directly with amyloid or Tau but
00:44:08
maybe have a little bit of a link with
00:44:09
hibernating bears obviously a
00:44:11
hibernating bear might get rather upset
00:44:13
if you awaken it and ask it to do
00:44:14
something it doesn't want to do like
00:44:16
provide a blood sample and we also know
00:44:18
that individuals with Alzheimer's
00:44:20
dementia they can also develop agitation
00:44:23
particularly later on in the disease
00:44:25
course where you know being asked to get
00:44:27
dressed or take a shower can be
00:44:29
confusing tasks and they can resist that
00:44:31
care or react sometimes verbally or
00:44:34
physically in an aggressive Manner and
00:44:36
at this point there are no approved
00:44:38
medications for the agitation or
00:44:40
aggression associated with Alzheimer's
00:44:42
dementia but that could change because
00:44:45
there are studies looking at specific
00:44:47
compounds this is a study of a drug
00:44:49
called Rex piprazole it's used currently
00:44:53
for treating disorders like
00:44:55
schizophrenia where people can have
00:44:57
confusion misperceptions that can be so
00:44:59
associated with agitation but these
00:45:02
individuals in this study all had
00:45:03
Alzheimer's dementia with frequent
00:45:05
aggressive behavior and they received
00:45:08
either Placebo or a daily dose of this
00:45:10
medication and they just measured how
00:45:12
much agitation
00:45:14
their study partner or family member
00:45:16
reported while they were receiving
00:45:18
either the active drug or the placebo
00:45:20
and in the end those who got the active
00:45:23
drug at either dose had fewer points on
00:45:27
this agitation scale it was about five
00:45:29
fewer points which means that either one
00:45:32
disruptive behavior might go from almost
00:45:35
a daily basis to almost not at all or
00:45:38
maybe five different behaviors that were
00:45:39
happening several times a week were now
00:45:41
only happening once a week so it could
00:45:43
have been a marked change in one
00:45:44
Behavior or a slight change in multiple
00:45:46
behaviors any of those would have a
00:45:49
translated into a five-point difference
00:45:51
so this looks promising but I think the
00:45:54
other thing that's very interesting is
00:45:55
that everybody's score on the agitation
00:45:58
scale dropped even even if they were
00:46:00
just receiving the placebo there was
00:46:02
actually about a 15 Point drop in the
00:46:04
placebo group alone and then an added
00:46:07
five-point drop in the treatment group
00:46:09
suggesting that just the benefits of
00:46:11
being in a trial working with folks who
00:46:13
can help understand these behaviors or
00:46:16
having the that interaction perhaps that
00:46:19
itself was associated with less
00:46:21
agitation and that's obviously hard to
00:46:23
replicate by simply giving someone a
00:46:26
medication every day so the FDA will
00:46:28
review this and it potentially may
00:46:30
become the first medication approved to
00:46:33
treat the agitation associated with
00:46:34
Alzheimer's dementia
00:46:37
um and then I'm going to just finish
00:46:39
with a final few slides looking at
00:46:41
non-medication trials some related to
00:46:44
Alzheimer's disease recently was
00:46:46
announced the result of a trial looking
00:46:48
at exercise the exert trial we know
00:46:51
exercise can have a lot of helpful
00:46:54
effects biochemically on the brain and
00:46:57
so the researchers wanted to know did
00:47:00
different types of exercise help
00:47:02
individuals with mild cognitive
00:47:04
impairment individuals showing some
00:47:05
memory changes but still independent in
00:47:07
Daily activity so not at the dementia
00:47:09
level but at the mild counter impairment
00:47:11
level and so they compared individuals
00:47:13
receiving an aerobic regimen of exercise
00:47:16
but they were targeting certain heart
00:47:18
rates versus those who did more toning
00:47:20
and stretching and they hypothesized
00:47:22
that those with the more aerobic
00:47:24
activity would show less cognitive
00:47:26
decline over time compared to just the
00:47:28
toning and stretching and as it turned
00:47:30
out both groups were remarkably stable
00:47:33
over 12 months whereas many individuals
00:47:35
with mild kind of impairment would
00:47:37
expect to have a decline over that
00:47:39
period of time and so the conclusion
00:47:41
would be even a modest or low level of
00:47:44
activity if it's stretching and toning
00:47:46
may help protect the brain cells or
00:47:48
maybe it was some other aspect of the
00:47:50
study because these individuals were
00:47:52
working at their local YMCA with
00:47:54
trainers on a regular basis so maybe it
00:47:57
was a social social interactions or some
00:47:59
other aspect that also helped to
00:48:01
preserve the memory over time because we
00:48:03
know from other studies those types of
00:48:06
activities social rather than just
00:48:08
physical activity can be helpful as well
00:48:10
so Dr hiroko Dodge who was previously
00:48:13
with our Michigan Alzheimer's center she
00:48:16
has done several studies looking at the
00:48:18
benefits of social contact to
00:48:21
individuals who either are older with
00:48:23
normal cognition or have this mild
00:48:25
counter impairment and in her study she
00:48:28
arranged volunteers to have regular
00:48:30
video sort of Zoom chats this was
00:48:32
planned pre-pandemic but became very
00:48:35
important when the pandemic hit because
00:48:37
they were able to continue the
00:48:38
intervention and so individuals either
00:48:41
receive these regular video chats plus a
00:48:43
weekly phone call or the control group
00:48:45
just had a weekly phone call and they
00:48:48
compare their cognitive scores and those
00:48:49
in the video chat group if they started
00:48:52
with memory impairment they actually
00:48:53
showed improvements on some of the
00:48:55
memory measures over the six and 12
00:48:57
months that these interventions were
00:48:59
being applied
00:49:01
and so you might say well gosh what if
00:49:03
we start doing all these things together
00:49:04
not just regular exercise but we engage
00:49:07
with others socially we follow a good
00:49:09
diet we treat our other health
00:49:12
conditions our blood pressure diabetes
00:49:14
what if we do all of these sort of
00:49:16
Lifestyle interventions what might the
00:49:17
outcome be then that's exactly what the
00:49:20
finished geriatric prevention trial or
00:49:22
the finger trial did where individuals
00:49:25
received either very structured
00:49:26
counseling about nutrition exercise they
00:49:29
were engaged in cognitive activities or
00:49:32
they were just sort of told we think
00:49:33
it's good for you to focus on these but
00:49:35
there wasn't any structured interaction
00:49:36
and these were older individuals at risk
00:49:39
for cognitive symptoms they followed
00:49:41
them over two years and showed better
00:49:44
test scores cognitively and those with
00:49:46
the more structured intervention and a
00:49:48
lot lower risk for certain health
00:49:50
conditions and chronic diseases as well
00:49:52
this was in Scandinavia but now as being
00:49:55
replicated across multiple locations so
00:49:57
there are multiple finger like studies
00:50:00
being done the one that's being done
00:50:02
here in the U.S is called the pointer
00:50:04
study an acronym for protecting
00:50:07
essentially the brain through lifestyle
00:50:09
interventions to reduce the risk of
00:50:12
cognitive impairment so a very similar
00:50:14
program where a large number of older
00:50:17
individuals who might be at risk because
00:50:19
of other health conditions or their age
00:50:22
or their family history but they either
00:50:24
receive a very structured lifestyle
00:50:26
intervention or just kind of a
00:50:27
self-guided one to see if we can
00:50:29
replicate that impact on cognitive
00:50:31
function and ultimately other health
00:50:34
conditions as well so this is an ongoing
00:50:36
study at several locations throughout
00:50:38
the US that we'll learn about more in
00:50:40
the coming years
00:50:42
but there's a lot more out there as well
00:50:45
so um you know I focused a lot on this
00:50:48
part of the biochemical pathway the
00:50:50
amyloid practice
00:50:52
aggregation or deposition talked a
00:50:55
little bit about this part the tangles
00:50:57
but there's lots and lots of other steps
00:51:00
that are going on in the brain when
00:51:02
someone is developing the pathology of
00:51:04
Alzheimer's and this slide isn't meant
00:51:06
to explain any one particular part of
00:51:08
them but just to say it's a complex
00:51:10
disease it's not just a simple thing
00:51:12
where one change happens there are a lot
00:51:14
of things going on which makes it
00:51:16
challenging but it also means there are
00:51:18
many potential steps for which we could
00:51:21
develop therapies or targets to
00:51:23
intervene and so we hope at the
00:51:26
University of Michigan to be involved in
00:51:27
some of these other treatments that
00:51:30
maybe aren't necessarily directly
00:51:31
attacking amyloid or Tau but other
00:51:34
important aspects in these biochemical
00:51:36
processes of Alzheimer's disease so I'll
00:51:39
finish with just mentioning some of the
00:51:41
studies that I've been involved with or
00:51:42
hope to to be involved with there are
00:51:44
many many more going on at the
00:51:46
University of Michigan through our
00:51:47
Alzheimer's Research Center that my
00:51:49
colleagues are leading so feel free to
00:51:51
take a look at our website if you want
00:51:53
to know what's happening right now we
00:51:55
were involved in the phase two trial of
00:51:57
lakinumab as I mentioned we've got a
00:52:00
prevention trial using the drug
00:52:01
solanasumab that is just finishing up
00:52:04
and one that is enrolling folks using
00:52:06
laquinimab as a prevention trial we have
00:52:09
other studies where we just follow folks
00:52:11
without any specific intervention but
00:52:13
using some of these specialized brain
00:52:14
schemes to track how things progress
00:52:16
over time some of these studies were the
00:52:18
ones that led us to understand that
00:52:20
amyloid can build up silently many years
00:52:23
before symptoms develop and in the
00:52:25
future we hope to be involved in some
00:52:28
really sophisticated trials where
00:52:31
compounds have been engineered to Target
00:52:33
you know very specific parts of this
00:52:35
pathway like these Sigma receptors here
00:52:37
and some using compounds that are a
00:52:39
little more I would call sort of natural
00:52:41
or organic like this medication or
00:52:44
compound called benefitiamine is kind of
00:52:47
an analog of thiamine a normal vitamin
00:52:49
that we have there are reasons to think
00:52:52
that in Alzheimer's disease there might
00:52:54
be insufficient levels of thiamine in
00:52:57
the brain or related compounds so giving
00:52:59
a simple sort of natural supplement
00:53:01
would that help slow down the
00:53:03
progression of Alzheimer's so there are
00:53:04
a couple trials planned using these
00:53:06
compounds that we hope to be involved
00:53:08
with and in the future one looking at
00:53:11
more specific therapies targeting the
00:53:13
Tau aspect in what's called a platform
00:53:15
trial where you can simultaneously
00:53:18
compare different Tau therapies or
00:53:20
anti-cal therapies against the placebo
00:53:22
rather than having to do separate trials
00:53:24
to sort of kind of speed up whether we
00:53:26
learn if a particular compound is
00:53:28
helpful or not so as I mentioned these
00:53:30
are just some of the things that we're
00:53:32
they're doing right now or hope to be
00:53:33
involved with many more available so
00:53:36
feel free to take a look at the Michigan
00:53:38
Alzheimer's disease Research Center
00:53:40
website specifically under the research
00:53:42
part to see what studies are enrolling
00:53:45
now and just keep an eye out there
00:53:46
because we add more all the time and
00:53:49
with that I will pause I think we've got
00:53:51
a few minutes if we are able to open up
00:53:54
questions
00:53:55
yeah absolutely thank you so much that
00:53:57
was a lot of really great information we
00:53:59
do have time for a couple questions so
00:54:02
if you do have a question you can go
00:54:04
ahead and put it in the Q a box and I
00:54:06
will pass that along to Judy
00:54:09
yeah
00:54:10
that box like we got one right away
00:54:14
already
00:54:17
this one says given that drugs have
00:54:20
demental side effects I'm interested in
00:54:24
finding out if the university has an
00:54:27
entertained or would entertain a
00:54:29
clinical trial to replicate results of
00:54:32
Dr Dale bresden
00:54:35
work that has produced stunning results
00:54:39
and not just slowing and advancing and
00:54:42
the advance of dementia but in reversing
00:54:45
the decline of cognition his protocol
00:54:48
isn't drug based and I would like to
00:54:50
know if the university would ever
00:54:52
consider such an approach to treating
00:54:54
Alzheimer's yeah I think that's a really
00:54:57
great great question so Dr bredesen has
00:54:59
designed
00:55:01
um not necessarily a specific regimen
00:55:03
but more of an approach to treat
00:55:06
Alzheimer's on an individual basis
00:55:09
taking into account a lot of the science
00:55:11
that says it you know there may be a
00:55:14
different aspect of Alzheimer's that's
00:55:16
more prominent in one person than
00:55:18
another so in one person there might be
00:55:20
a lot more inflammation and another
00:55:22
person it might be more oxidation or
00:55:24
some other component and so the idea of
00:55:27
his approach is to do a lot of blood
00:55:31
work and other markers related to these
00:55:33
and sort of design a specific
00:55:35
intervention tailored to that person's
00:55:38
blood work and it also involves aspects
00:55:41
of diet or sometimes even caloric
00:55:43
restriction like not eating During
00:55:45
certain hours of the day so it's not a
00:55:47
it's not a one-size-fits all but it's
00:55:49
sort of an algorithm and so that makes
00:55:51
it hard to study you know how do you
00:55:54
study it when each person is going to
00:55:55
get a little different combination of
00:55:58
supplements or things like that but I
00:56:01
think it really does deserve study
00:56:02
because right now what we're hearing is
00:56:04
largely sort of and anecdotal reports
00:56:06
not really rigorous scientific results
00:56:08
but I think it would have to be a
00:56:10
collaborative effort probably something
00:56:12
more than any one Center could tackle
00:56:15
but you'd have to think about it
00:56:17
creatively how do you what's your
00:56:19
comparison group so maybe you look at
00:56:21
all the different possible supplements
00:56:24
that might be recommended and in one
00:56:26
group you say okay we're going to do a
00:56:27
very careful match to the blood work and
00:56:30
the other group we're going to randomly
00:56:31
assign some combination to see is it
00:56:34
really that individual tailoring that
00:56:36
makes a difference or is it just doing
00:56:37
something focusing on your health helps
00:56:40
you be better and it really doesn't have
00:56:41
to do anything with a specific compound
00:56:43
so I think that's a great question but
00:56:45
not a simple answer
00:56:48
all right I'm gonna go into another
00:56:51
question having read Sebastian Walsh at
00:56:54
all's
00:56:55
bmj editorial La Canada map and
00:56:58
Alzheimer's disease with the subtitle
00:57:01
new trial reports little to celebrate
00:57:04
for patients and carriers I'd like to
00:57:07
hear Dr heidebring's perspectives on the
00:57:11
clinical meaningfulness
00:57:13
of the amount of reduction in cognitive
00:57:15
decline based on the clinical dementia
00:57:19
rating
00:57:19
that is reported in the pivotal trial
00:57:22
which seems to be an important
00:57:24
consideration along with the trial's
00:57:26
safety findings the authors conclude
00:57:30
against the scale and severity of
00:57:34
adverse
00:57:35
events and substantial practical
00:57:38
barriers to widespread use lecanomev is
00:57:42
unlikely to represent a favorable risk
00:57:44
benefit balance for patient or value for
00:57:48
money for Health Systems
00:57:50
wow that was a mouthful of a question
00:57:53
but it was very well um proposed because
00:57:57
I think that's really the key question
00:57:58
is uh we have a drug I think there's
00:58:02
consistent evidence of a benefit in
00:58:05
terms of slowing progression but
00:58:07
numerically that benefit is small and we
00:58:11
have side effects that we know again
00:58:13
most of the time those are clinically
00:58:16
silent but if not adhere to carefully or
00:58:20
monitor carefully they could become more
00:58:22
problematic and so ultimately what's the
00:58:24
risk benefit and I think that answer is
00:58:26
going to be different in different
00:58:28
people I think one way of posing it is
00:58:30
the way I sort of suggested earlier
00:58:33
would it have been worth it to you to be
00:58:35
coming in every two weeks for this
00:58:36
infusion if now at the end of the study
00:58:38
you were back to where you were six
00:58:39
months ago and I think some people would
00:58:41
say absolutely I could be doing this for
00:58:43
six months longer I could be doing that
00:58:44
I could be independent in these
00:58:46
different ways and what's you know
00:58:47
what's the value of Independence how do
00:58:49
you measure that other people would say
00:58:51
I didn't really feel that much different
00:58:53
six months ago I'm not changing much I'm
00:58:57
not sure it's worth it so again it's a
00:58:59
very hard question to answer I think
00:59:00
everyone's going to have their own take
00:59:02
and we don't know whether that benefit
00:59:04
might be greater as time goes on that's
00:59:08
an unanswered question at this point I
00:59:10
agree that this is not going to be the
00:59:12
way we treat Alzheimer's logistically
00:59:14
it's just not a drug we can administer
00:59:16
to the numbers of people who are even
00:59:18
you know potentially falling into that
00:59:20
eligibility range but I think it's a
00:59:23
breakthrough in saying you know we can
00:59:25
do something on the ambly basis that
00:59:27
modifies we just need to develop even
00:59:29
more powerful I guess and safer drugs
00:59:32
ultimately
00:59:34
great uh do you have time for a few more
00:59:36
questions Judy sure sure okay great
00:59:39
um are there any trials looking at the
00:59:42
quality of life
00:59:44
um often that is an embedded measure in
00:59:47
the clinical trials so that lacena mab
00:59:50
study did include measurements where
00:59:52
they asked both the participant about
00:59:54
their quality of life trying to rate it
00:59:56
numerically had their study partner
00:59:59
provide a sense of what they thought the
01:00:01
participant's quality of life was like
01:00:03
and they also had the study partner rate
01:00:05
their own burden so to speak as a
01:00:08
caregiver how much you know of your time
01:00:10
do you think is spent providing care for
01:00:12
this person and is that in any way you
01:00:14
know a detriment and so those caregiver
01:00:17
burden and Quality of Life ratings were
01:00:19
tracked those haven't been published yet
01:00:22
to my understanding but they did show a
01:00:24
difference in the treatment group versus
01:00:26
duplicity group again a small difference
01:00:28
but those are things that are really
01:00:30
hard to to to measure trying to put
01:00:33
numbers on on quality of life but you're
01:00:35
right I think that's an important aspect
01:00:36
of trying to understand the
01:00:38
meaningfulness of scales like that CDR
01:00:42
all right how long does the removal of
01:00:46
amyloid last after treatment another
01:00:49
great question it probably lasts quite a
01:00:53
bit longer than just you know the last
01:00:55
infusion and
01:00:57
um we know that in part from individuals
01:01:00
who participated in the phase two study
01:01:03
of locina mab
01:01:05
um some got the active drugs at
01:01:06
different doses some got the placebo
01:01:08
they had pre-imposed pet scans and then
01:01:11
some were invited later on to enter an
01:01:14
open label but there was a lag period
01:01:16
between when they finished the phase two
01:01:18
and when they finish the open label what
01:01:20
everyone got the drug and so if they got
01:01:22
a new pet scan when they entered the OPA
01:01:24
label you could say if they'd gotten the
01:01:26
active rug and their and their amyloid
01:01:28
was lower did it stay lower for that
01:01:30
year or two years when they weren't
01:01:32
receiving further therapy and the answer
01:01:34
was yes it did seem to stay low so that
01:01:37
is encouraging that maybe you don't need
01:01:39
to keep dosing forever with these agents
01:01:42
on the other hand if you track their
01:01:44
cognition there was a sense that if it
01:01:47
was being slowed down that benefit was
01:01:50
starting to slide when they weren't
01:01:52
receiving the treatment so so yes we
01:01:54
were able to keep the amyloid low even
01:01:56
without continuous therapy but one of
01:01:59
the benefits persist is a harder
01:02:00
question but researchers trying to
01:02:02
answer that right now
01:02:06
all right
01:02:07
why did the number of participants
01:02:10
reduce so much during the study of
01:02:13
educatamab
01:02:15
Oh you mean looking at the numbers I
01:02:16
don't know if it's referring to looking
01:02:17
at the numbers of people at different
01:02:19
time points well
01:02:21
um if that's the question
01:02:23
um because the styles were halted early
01:02:25
not all people made it to the 18-month
01:02:28
time point that they designed and
01:02:30
everybody enters the trial at a
01:02:31
different time you don't enroll all 3
01:02:33
000 people at day one some people
01:02:35
enrolled you know at one point other
01:02:37
people a few months later and other
01:02:38
people a few months later you continue
01:02:39
to accumulating people they halt the
01:02:41
trial part way through some people at
01:02:43
that point have made it to 18 months but
01:02:45
it's only a fraction of those that they
01:02:47
originally intended to follow the whole
01:02:49
way through so the numbers at each time
01:02:51
point is smaller and smaller because the
01:02:53
trial is halted early so fewer and fewer
01:02:55
people had the opportunity to get to
01:02:57
those later time points and there are
01:02:59
other things that happen too people drop
01:03:00
out of the trials for any number of
01:03:02
reasons so it's common for up to maybe
01:03:05
15 20 of people not to finish a trial
01:03:09
for all sorts of reasons
01:03:11
all right
01:03:13
wasn't there a research peer-reviewed
01:03:16
Journal article where an invested an
01:03:19
investigator manipulated data regarding
01:03:22
amyloid plaque will that affect any
01:03:24
amyloid clinical trials yeah that's
01:03:26
another great question that was another
01:03:28
big news story in the past year it was a
01:03:32
publication looking at a specific
01:03:35
form of amyloid where the thought was
01:03:39
that the actual scientific data had been
01:03:43
either manipulated or the same result
01:03:45
was published in multiple ways and not
01:03:47
really reflecting unique unique data
01:03:51
many people had actually questioned that
01:03:54
original publication because they they
01:03:56
was sort of identifying a toxic species
01:03:58
of the amyloid several Labs early on and
01:04:01
said we really can't replicate that it
01:04:04
was kind of one piece in the big amyloid
01:04:07
puzzle and no specific therapies were
01:04:10
ever designed towards that specific
01:04:12
species in part because the early data
01:04:14
couldn't be replicated so the fact that
01:04:16
that data May well have been falsified
01:04:18
is a huge you know it's a huge
01:04:20
disappointment and that you know
01:04:21
scientific Integrity is so important so
01:04:23
that really does need to be reviewed and
01:04:26
corrected but fortunately it didn't
01:04:28
really change the larger course of
01:04:31
treatments geared towards amyloid
01:04:33
okay all right here's another one
01:04:36
because social contact is able to slow
01:04:40
decline of memory does the exert or
01:04:43
other exercise trials have a beneficial
01:04:46
effect merely due to social contact with
01:04:50
exercise coaches is this why the balance
01:04:53
group showed as strong results as the
01:04:57
cardiovascular exercise group I think
01:05:00
that is an unanswerable question because
01:05:02
you couldn't separate out the social
01:05:04
contact from the exercise since all of
01:05:07
these exercise sessions were being
01:05:08
conducted with that social contact piece
01:05:11
of it working with a YMC trainer for
01:05:13
example so you'd have to design a
01:05:15
separate experiment where you can still
01:05:18
monitor people and know that they're
01:05:19
exercising you know like they have to
01:05:21
turn on a zoom camera with the exercise
01:05:22
and someone just you know behind the
01:05:24
scenes documents that they don't they
01:05:26
are exercising but isn't actually
01:05:27
interacting with them during their
01:05:29
exercise to be able to separate that
01:05:32
component out so we don't know which of
01:05:34
those components led to the benefits
01:05:36
whether it was to come combination
01:05:37
either one separately can't answer that
01:05:40
question right now
01:05:41
all right just a comment I have observed
01:05:45
a significant provement of
01:05:48
once winter ended last year and he
01:05:51
resumed considerable biking and weight
01:05:54
workouts that along with sunshine and
01:05:57
more social interaction really seemed to
01:05:59
help I'm glad to hear that it is not my
01:06:01
imagination now we're looking into
01:06:04
cardio equipment for Indoor Winter use
01:06:06
we already have a weight machine perfect
01:06:09
perfect maybe you could describe that
01:06:11
what your husband went through was sort
01:06:12
of like that bear Awakening from
01:06:14
hibernation it was you know doing
01:06:15
something biologically that was helpful
01:06:18
as he got more light exposure more
01:06:21
exercise all those other activities so
01:06:23
good for you
01:06:24
all right what are the risks of taking
01:06:27
uh
01:06:30
okay I can't pronounce it betho tiamine
01:06:34
oh the benphotiamine yeah which is
01:06:37
available as a supplement if it doesn't
01:06:40
help if it doesn't prove beneficial
01:06:42
could Alzheimer's patients take it just
01:06:45
in case there might be a benefit yeah I
01:06:48
mean in theory that's true with a lot of
01:06:50
supplements that people are proposing
01:06:53
that might be helpful whether it's a
01:06:54
vitamin supplement an anti-inflammator
01:06:57
you know things that are over the
01:06:58
counter
01:06:59
um we'd really like to know because some
01:07:02
people are out there selling quite
01:07:03
expensive version of these things and so
01:07:06
um rather than just saying what do we
01:07:08
got to lose we'd really like to know
01:07:11
um partly because we want to know if
01:07:13
it's helpful to prescribe it but also to
01:07:15
know in a rigorous way are there side
01:07:17
effects because without those studies
01:07:19
we're just relying on people's just sort
01:07:21
of anecdotally saying hey I tried it and
01:07:23
it bothered my stomach which is probably
01:07:24
the most common side effect that we hear
01:07:26
with most of these supplements but we
01:07:28
wouldn't know without rigorous study are
01:07:29
there electrical effects on the heart
01:07:31
are there interactions with other
01:07:33
medications so that's why we really like
01:07:35
to have that rigorous study to say not
01:07:37
only is this that you know not only does
01:07:38
it help people but we know it's safe to
01:07:40
take in combination with other things
01:07:41
too
01:07:43
okay one last question
01:07:46
um
01:07:47
uh Risperdal worked wonders for my loved
01:07:51
one with A.D as far as agitation and
01:07:55
angry outbursts it was a game changer
01:07:57
have you ever recommended Risperdal for
01:08:00
those same behaviors
01:08:02
um yes Risperdal is sort of in the same
01:08:05
category as the drug that I mentioned
01:08:07
and so we will in many cases use those
01:08:11
types of medications because we know on
01:08:13
an individual basis they can be helpful
01:08:16
unfortunately there isn't a magic one
01:08:18
that works for every person every time
01:08:20
and you know that's partly why there
01:08:22
hasn't been a drug that's approved yet
01:08:24
because when you study groups of people
01:08:25
they don't all behave the same way
01:08:28
um but yeah Simpsons we don't have any
01:08:30
technically approved therapies for the
01:08:32
agitation and behavioral challenges we
01:08:34
resort to using medications that we
01:08:36
think might be helpful even without that
01:08:38
FDA stamp of approval
01:08:41
okay just one more I I fibbed that's
01:08:44
perfect
01:08:44
is it true that general anesthesia
01:08:47
causes pitau to elevate oh I think I
01:08:51
would say
01:08:52
um I will defer on that one I mean there
01:08:54
are a lot of there are a lot of
01:08:56
interesting questions about anesthesia
01:09:00
and whether its effects are only
01:09:03
temporary you know turning the mind off
01:09:05
and you know rebounding afterwards or
01:09:07
whether there are any links to any
01:09:09
Alzheimer's type changes some of the
01:09:10
things that I had heard about were
01:09:12
related really more to
01:09:14
inhaled anesthetic agents that we don't
01:09:16
use anymore so at this point I would say
01:09:18
there's not anything convincing in my
01:09:20
mind that an anesthesia is a direct risk
01:09:23
for Alzheimer's changes but a lot a lot
01:09:25
more is being done to look at that
01:09:28
okay I think that is all that we had
01:09:32
um be on the lookout for an email that
01:09:35
will come out
01:09:37
um um I will be sending out an
01:09:38
evaluation for this so it'd be really
01:09:40
helpful
01:09:41
um we like to make sure that we're
01:09:43
serving everybody uh properly and and
01:09:46
I'm glad everybody had a chance to
01:09:48
attend so thank you so much for coming
01:09:50
all right thanks everyone

タグ

Alzheimer
Investigació mèdica
Anticossos monoclonals
Plaques amiloides
Assaigs clínics
Qualitat de vida
Neurodegeneració
Prevenció
Medicina
Salut mental