3.3 Aim to Get Better at Understanding Dementia Blog#3: Alzheimer's Disease: Where are we with drug treatments?
AIM to Get Better at Understanding Dementia Blog #3
On 10th December,
I attended an online webinar, hosted by Alzheimer’s Disease International.
It was their inaugural “End of Year Forecast”
webinar, entitled “Translating the
Alzheimer's Treatment Revolution into Real World Solutions”
Professor Jeff Cummings is
possibly one of the most intelligent humans on the planet yet he explained very
complex issues around current and future drug treatments for Alzheimer’s
Disease (AD) in a way that even I understood! It probably helped that his
amazing accent reminded me of “Deputy Dog” (for those of you old enough to
remember the 1970’s cartoon character) and therefore very easy to listen to! I
have tried to use the same language he used in my notes below. If you would
prefer a more academic overview, you can read the academic paper on which his
talk was based by using the link below:
https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.12465
ADI have produced their own blog
about the event, which includes a link to a recording, so if you would rather
read their blog than mine, or watch the actual webinar, click below:
Here are my notes from the
webinar:
· The whole webinar used just one slide, (see below),
giving an overview of the 127 drugs for AD currently being tested in clinical
trials.
· The majority of these are currently in phase 2
trials.
· It currently takes 10 years for drugs to move from
phase 1 to phase 3 and approval; it is essential we find a way to reduce this
timescale.
· Most of the progress is currently being made with
drugs administered intravenously (IV) or subcutaneously (SC) and one of the
challenges is to get these developed into a form that can be taken orally
(which was the same with cancer treatment research several decades ago)
· The trials in the blue area are drugs being
developed specifically for neuropsychiatric symptoms (agitation, distressed
behaviours, hallucinations). One of these drugs was approved in USA in 2024,
which is a major breakthrough in reducing antipsychotic use in dementia care.
· The trials in the orange area are focussed on
symptom reduction and the drugs in the purple area are aimed at slowing disease
progression. 2024 has seen major breakthroughs in the approval of
drugs that can slow disease progression, for the first time ever!
© J Cummings; M de la Fleur, PhD, Illustrator. Full
publication available at https://doi.org/10.1002/trc2.12465
· The trials with a red box next to them are focussed
on Amyloid – specifically, triggering the body’s own immune system to break
down the Amyloid plaques. One of the challenges with this is that these drugs
don’t just trigger the breakdown of proteins in the brain – it can also cause
the breakdown of proteins in blood vessels, increasing the risk of
blood “leaking out” of the blood vessels into the brain. This is most likely to
happen if people carry the APOE4 gene (the gene that predicts the risk of AD),
If we know who is most vulnerable to experience these side effects, we can take
action to reduce the risk.
· The trials with a dark green square next to them
represent trials focussed on the protein Tau. It is currently thought
that limiting the build up of Tau in the brain will have far more
effect on disease progression than limiting the build up of Amyloid. This
is therefore a vital area of research.
· COMBINATION THERAPY IS COMING! As with treatments
for cancer and HIV, it is highly likely that we will soon be using treatments
that focus on both Amyloid and Tau.
· 30% of the dots on the graphic represent trials
that are “repurposing” drugs. For example, Donepezil and Memantine are being
developed as “depot injections” which can be given monthly, for those people
who may not remember to take oral medications as prescribed. Parkinson’s drugs
and some cancer drugs are being trialled to see if they can be used effectively
in AD. This is really important as it will drastically reduce the time to get
to phase 3 and approval – don’t need to go through animal testing and phase 1
trials because they have already gone through these phases for a different
purpose.
· Semaglutide , the drug being used for diabetes and weight loss,
is being investigated for its possible effect on AD, both for its
anti-inflammatory and metabolic properties. It has already be shown to a very
effective anti-inflammatory in the treatment of kidney disease and heart
disease. We will know by the end of 2025 if it will have a
positive effect on AD, but it looks very promising.
· There are even clinical trials going on looking at
the potential effect of caffeine (effects on Tau), Nicotine, Cannabinoids
(treatment of agitation), Chinese medicine.
· Use of psychedelic medications is also being
trialled on people with PTSD, and people with PTSD and dementia.
Diagnostics
· We are very close to having blood tests to diagnose
AD, by looking at levels of Tau, Amyloid and inflammatory markers. This is
essential, partly because blood tests are much more accessible, and therefore
equitable than scans which are expensive and complex to carry out. Also, many
GP’s will mis diagnose AD when the person has another form of dementia, so it
will ensure targeted treatments can be given. In USA, the FDA has approved the
use of blood tests for eligibility to take part in clinical trials.
Genetic testing:
· Although useful in identifying risk, not useful in
diagnostics.
· Looks for APOE4 gene. If you have 0 copies of the
gene, you still have a 15% lifetime risk of developing AD. If you have 1 copy
(from one parent) you have 30 - 40% lifetime risk. Risk. If you have 2 copies
(one from each parent) your risk is 90% +.
· Not really helpful to know your risk until we have
more effective treatments! There is not really anything you can do about a
genetically inherited risk – much more helpful to focus on the 14 reversible
risk factors (World Alzheimer’s Report 2024).
Final reflections
This was one of the most
fascinating updates on dementia I have ever attended, and I came away feeling
inspired.
I will definitely be looking out
for more ADI webinars! Informative and accessible!
Mary-Joy
Albutt 26.1.25
©AimtoGetBetter2025
For more blogs by MJ, please
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https://maryjoyalbutt.blogspot.com
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