What's up with Alzheimer's research?

So I haven't posted for a while.  One of our children was married over in Seattle, and, as an elder in our church, I've had a lot to do there.  And then I sometimes have slow periods finding content I think you'd find interesting.

For those interested, I've given up on acupuncture for insomnia.  At least according to my Fitbit, I had some minor, transitory improvement in sleep quality, but I can't really say it did anything for my insomnia.  So I just continue to adapt to life the way it is.

But what’s been going on in the world of Alzheimer’s research?  Are there new drugs coming?  Any breakthroughs in understanding the disease?  Well, here are a few items of interest that I’ve noticed.  It’s certainly not complete, and the items are in no particular order.  Spoiler alert: there are no breakthroughs.  But these were interesting to me. 

Fosgonimeton, a drug with a history of safety, was expected to improve cognitive and daily functioning in adults with mild to moderate Alzheimer’s disease.  But it failed to meet its goals in a recent second phase of a three-phase clinical trial.  The drug was being developed by Athira Pharma.  It is not designed to remove amyloid plaques.  After all, removing amyloid plaques may not be the best approach to treating the disease anyway.  There were some positive improvements in some of the test subjects, so this drug may not be dead yet.

Alzamend Neuro and Massachusetts General Hospital are preparing to conduct a Phase 2 clinical trial of a candidate treatment code named AL001.  This is an oral therapy being developed for dementia related to Alzheimer’s disease.  It will use a new system for delivering lithium to the brain.  So far, pre-clinical studies and the Phase 1 trial have demonstrated its safety with a small group of test subjects … the main purpose of Phase 1 trials.  But I don’t see any claim that the earlier trials found any improvement in memory and cognition.

Amylyx Pharmaceuticals is testing an oral therapy code named AMX0035.  In a recent trial, the study drug reduced the levels of several biomarkers associated with Alzheimer’s disease.  A company press release stated, “The results from this exploratory analysis suggest that AMX0035 engages important pathways implicated in the [development] of Alzheimer’s disease and other neurodegenerative diseases.”  Despite these results, data from a Phase 2 trial showed that six months of oral treatment failed to slow cognitive decline compared with a placebo.

In a proof-of-concept clinical trial, treatment with a prospective pharmaceutical, CT1812, previously called Elayta, slowed the decline of cognitive function among adults with mild to moderate Alzheimer’s disease.  That’s according to results after about six months of treatment at trial sites in the U.S., Europe, and Australia.  In a company press release, Lisa Ricciardi, president and CEO of CT1812’s developer Cognition Therapeutics said, “The trial showed that after 182 days of treatment, [CT1812] demonstrated evidence of clinical improvements on cognition coupled with a favorable safety and tolerability profile.”  Ricciardi added that the findings “will inform dose selection and provide a foundation for advancing [the therapy] to the next stage of clinical development.”  Of course, a “proof of concept trial” comes even before a Phase 1 trial.  So this one has a long way to go.

As I found out when I was first diagnosed, donepezil (Aricept) can cause significant gastro-intestinal issues.  That’s why I stopped taking it.  This is a problem with this whole class of drugs, the acetylcholinesterase inhibitors.  Now, the FDA has approved the oral therapy Zunveyl (benzgalantamine), previously known as ALPHA-1062.  Zunveyl carries the acetylcholinesterase inhibitor galantamine through the digestive track and then into the blood stream before releasing it.  This bypasses the stomach issues.  According to Dr. Elaine Peskind, (with whom I am acquainted), an Alzheimer’s expert at the University of Washington School of Medicine in Seattle, approval of the drug “marks a meaningful step forward in improving the quality of life for those living with Alzheimer’s and their families.”

Administration of Montelukast oral film, an existing therapy being repurposed by Intelgenx to treat mild to moderate Alzheimer’s disease, led to significant improvements in patients’ cognition versus a placebo.  This was according to a report of a Phase 2 clinical trial.  The drug was approved years ago as a treatment for asthma, but it may have value in treating Alzheimer’s and Parkinson’s diseases.  But there was a confusion factor in the report summary: “[W]hen considered across all doses of [Montelukast], no benefit to general cognition was observed when compared to change under placebo.”  Go figure.

A New Drug on the Horizon?

Troriluzole.  I've never heard of it before.  But it just popped up on my radar as a new treatment candidate for Alzheimer's disease.  It's currently being investigated as a treatment for some forms of cerebellar ataxia (like mine?), obsessive-compulsive disorder, and some other neurological disorders.  It's a formulation of the existing drug riluzole that is used to treat ALS -- Lou Gehrig's disease.  The re-formulation is to increase its bioavailability.  

But suddenly, a study from Auburn University in Alabama, published in the Journal of Neurochemistry, indicates that it may treat underlying mechanisms in Alzheimer's disease ... in mice.  Mice again, but you have to start somewhere.  At least we already have a lot of experience with the riluzole from a safety standpoint.  And administration of the drug to genetically modified mice -- modified to produce a disease like Alzheimer's -- improved their memory and cognition.

It's probably a long way from the work with mice to an approved treatment.  But what's interesting about this investigation is that it may lead to better insight on how Alzheimer's actually works.  It's increasingly evident that removing amyloid plaques simply addresses symptoms, not the underlying disease.  But most of the drug strategies getting attention are about removing plaques.  And sometimes removing plaques doesn't even help.  So it may be that, not only do we get a new drug that will deal more directly with the underlying disease, but we will learn more about what the disease even is.  (Because we don't really know!)

Here's an article about the research.  But beyond what I've said here, the discussion gets pretty deep.

Whither the Acupuncture?

Back on August 10, we wrote that I had begun getting acupuncture treatments for my insomnia.  At the time, I had completed one treatment, and believed I had gotten some improvement.  Not that I didn't wake up in the middle of the night as in the past, but that first night my Fitbit recorded significant improvement in sleep quality.  So I thought it was worth continuing to see what would happen.  (Some of you suggested this was a placebo effect, and -- I don't know -- maybe you're right.)  The research I cited in my August 10 post used six treatments as a benchmark for evaluation.  I thought that was a good goal for me.

Except that I need to be good at counting to make sure I get all six...

As of last Friday, I thought I had completed the six treatment goal.  Aside from the initial boost in sleep quality, I didn't feel that my sleep had improved.  I still woke up in the middle of the night, and my sleep scores were back to being pretty bad.  So I said that last Friday's treatment would be my last.  Except that was only five treatments, not six.  (I don't count good.)

My pattern is to get to sleep relatively easily, but then wake up at 1 or 2 a.m.  When I wake up, I REALLY wake up, and in an unpleasant way.  It's painful even just to lie there.  So, I would get up and take care of a few things, but I had always been able to go back to bed and get back to seep after being up for one and a half hours.  This might yield six and a half hours of sleep.  Not ideal, but I can live on that.  But for the past few months, getting back to sleep has been nearly impossible.  I would feel unwell during the day, and I thought I could just nap after noon.  Aside from a schedule that didn't accommodate naps well, I usually couldn't even get to sleep for the nap.  If I could get to sleep, it would be only for 15 minutes or so -- not making up for what I lost the night before.

After cancelling my subsequent appointments, it occurred to me that, after starting the acupuncture, I have recently actually been getting back to sleep at about 4 a.m. and been sleeping OK after that.  Waking up last night was quite unpleasant, but I went back to bed after an hour and a half, and my Fitbit says I actually got seven hours with a (for me) good sleep quality score.  This is a more sustained improvement -- it's been a long time since I've seen that.  So maybe I was premature on cancelling my appointments, and I should reschedule.  Stay tuned.