The Heat Is On

Aducanumab, they wayward child of Alzheimer's disease treatments, will get her day in court on November 6.  Here is the entry in the Federal Register announcing the meeting when the FDA will consider Biogen's request for approval.  And the pressure on the FDA to approve is considerable.  

What must the FDA consider in their decision?  First is safety, and the second is efficacy.  Is it safe, and will it work?

First -- safety:  The monoclonal antibody is known to cause microhemorrhages in the brains of some test subjects.  None of these had serious consequences, but the test subjects were taken off the treatment immediately when the hemorrhages were detected.  All test subjects required frequent MRIs to detect the hemorrhages, and it's anticipated that anyone treated with an approved drug will require the same MRI regimen.

Second -- efficacy:  During Biogen's trial, fear of microhemorrhages caused the researchers to significantly cut the dose for many of the test subjects.  When the data was analyzed at the end, the researchers had a mixture of data from both doses.  From this, they initially concluded that the treatment was ineffective and declared it a bust.  But the researchers worked late into the night to discover that, if you broke out the test subjects who were exposed to the full dose, maybe it worked after all.  It wasn't a cure, but it appeared to be the first pharmacological treatment that would actually attack the disease mechanism and slow its progress.

There are some who believe that the trial was botched, and they should have a do-over.  But that would take four more years.  Others say that we understand both the risks and the potential well enough that we should just go ahead and make it generally available.  We'll see what they decide.

I actually first began hearing back in 2016 that we should just make it available before even performing the drug trial.  I don't know if I could find the article now, but I believe I saw a doctor making the case for it in Parade Magazine.  The thought was that Alzheimer's disease is so onerous and so many victims would not outlive the trial that it should be available to anyone willing to take the risk.  That didn't happen, but I'm guessing that the FDA will approve it without the customary level of evidence for its efficacy.  It's likely they will agree with Biogen that the side effects and risks are sufficiently well understood to let it go forward.  

Join the Polar Bear Club to beat your Alzheimer's!

RNA binding protein 3, or RBM3 is a protein whose design is specified in the RBM3 gene.  The gene is especially "expressed" -- or used to generate the RBM3 protein -- when the body is exposed to cold stress.  It's notably present in winter-time hibernating mammals.  What RBM3 does in different cells is complex, sometimes doing good things, sometimes doing bad things.  It can work against some cancers, but it can promote others.  Can it have an effect, for better or worse, on your brain cells? 

My pastor sent me this article about research with mice showing that perhaps driving body temperature down and then raising it carefully may combat dementia.  The article was based on research discussed in Nature Reviews Neurology which purported to find that mice with a disorder similar to Alzheimer's disease in humans experienced repairs to some neurons when their body temperatures were radically decreased and then carefully raised.  The RBM3 thus generated apparently repaired synapses and altered the course of their diseases.  They said that RBM3 in their research "prevented loss of synapses and alleviated behavioral and memory impairments." 

What got the researchers looking into this?  It began with looking into the possible health benefits of the cold water dips of the Polar Bear Club and long-standing rumors that plunging into freezing water somehow benefited people's health.

Do you need to join the Polar Bear Club to get your RBM3 busy?  One idea is that a virus can be used to artificially insert RBM3 protein into cells.  So maybe you can skip the dip.

So how far away is an RBM3 therapy?  Pretty far.  This research is very preliminary, and it only points to possibilities. 

Here's the standard disclaimer on mouse models:  Mice are not people.  In the past, research with mice has generated a great deal of excitement until it was learned that a phenomenon with mice could not be replicated in humans.  Also, mice don't get Alzheimer's disease.  Instead, their genome (their DNA) can be modified to produce a disorder similar to Alzheimer's disease in humans, but it's not the same.

Look into my eyes ... you have Alzheimer's ...

We have discussed many times the importance of early detection of Alzheimer's disease.  It is in the early stages, perhaps years before symptoms appear, that interventions are thought to be most effective.  This includes lifestyle interventions, but it will also likely be the case with drug interventions, such as the now-promising aducanumab.

Also, early (and accurate) detection is important to Alzheimer's research.  The younger a test subject is, the less likely the test results are to be confused by other brain pathologies that emerge as we get older.  People (like me) who first display symptoms at 65 or older, likely were already developing the disease at 50.  But so far, there is no reliable test to identify the disease at this age.

We seem to be on the verge of FDA approval of one or more blood tests for early detection of Alzheimer's disease.  These will look for the presence of beta amyloid in a blood sample.  Beta amyloid in the blood has been found to correspond to the development of Alzheimer's disease.  But are there other ways of detecting the amyloid?  It seems there is at least one other.

A research study published in the November 20, 2019 issue of the journal ACS Chemical Neuroscience described a process for identifying beta amyloid in the retina of the eye.  The researchers found that, when they shone a light on the retina, the beta amyloid molecules (due to their unique shape and small size) scattered the light in a peculiar way.  This type of scattering is called Rayleigh scattering, and it is what causes scattered sunlight in the sky to present as the color blue.  In the case of the sky, the blue light is scattered across the sky by the small air molecules.  The small amyloid molecules can apparently do something similar with light shone on the retina.

Once fully developed, it seems this process will provide an easy and (relatively) inexpensive way of identifying the onset of Alzheimer's disease early in the pathology.  It may resemble the test you get for glaucoma at your optometrist. 

So what is to be done with this development?  In a recent announcement, the Canadian AI medical imaging company, Retispec, announced that they are partnering with Gentex Corporation to develop the technology and move it into use.  Gentex engineers and manufactures electro-optical equipment for a variety of industries -- such as the device that dims the rear view mirror in your car at night. 

How long will this take to bring an approved device to market?  I don't know, and I didn't get any insight from the literature the partnership has released.  Considering how advanced the blood tests seem to be (just awaiting FDA approval), I think the blood tests will be available first.

Thank you so much!

Our Walk to End Alzheimer's is now complete, and I am so gratified by the support that Amy and I received from so many of you!  I don't know how they calculate this or where the bars are, but they classified me as a "top fundraiser" and "grand champion."  So thank you so very much!

Your contributions go, of course, to a very good cause.  The Alzheimer's Association is a major funder of Alzheimer's research, and they provide many vital services to people with Alzheimer's disease and their families.

While the Walk is over, they will keep my personal contributions web page open for belated contributions until late December.  

Not yet history -- Eastern Washington Virtual Alzheimer’s & Dementia Conference

Now that the dementia-friendly conference, my Community Engagement Series talk, and the Walk to End Alzheimer's are behind me, the next focus is on the Eastern Washington Alzheimer's and Dementia Conference.  For the second year in a row, I am on the planning committee, but with a lesser role compared to the other events.  Last year, I was the event photographer, which went OK.

The conference is scheduled for October 29, and registration is now open.

This is a big event each year for this side of the state (the desert area east side of the Cascade Mountains), but the virtual approach is, of course, new.  But virtual conferencing seems to be working out in other venues with sometimes significantly increased participation.

The Eastern Washington conference focuses on the needs of both caregivers and medical professionals. 

Dementia Friendly Communities Conference 2020 is now history

The Collaborating for a Dementia Friendly Washington conference came off quite well, and I'm very happy to have been a participant--not only in its planning and execution, but also to have been a speaker.  We had about 280 registered participants, with maximum attendance at one time of 200.  All registered participants have the option of viewing the whole conference for some period of time into the future, so those who couldn't get off work to attend will still be participating.  Of course, my speaking was limited to just three three-minute statements, but I think I made good use of the time allotted.

Some of what I said is available on YouTube, but not all.  Here is the link to the first day panel discussion, where three of us reflected on the keynote speaker's talk. I appear at 47 minutes and then at 59 minutes.  I was allocated 3 minutes each time.

For those interested, here is all of what's publicly available on YouTube.

Walk to End Alzheimer's 2020 now history...

Amy and I participated in the Walk to End Alzheimer's this past Sunday.  It was a very pleasant experience, and I was gratified to have been supported so well by so many of you.  I was rated a "Top Fundraiser" and a "Grand Champion."  Not sure what the criteria for these two badges are, but I'll take it.

Because of the covid, it was not a group walk.  There was an on-line opening ceremony, and then we were to all walk about two miles in our neighborhoods.  Amy and I walked along the river.

Again, thanks to all who supported us in this!  Your contribution will not only help in the search for a cure, but it will also provide direct support to families struggling with the challenges that Alzheimer's disease brings.

Whither Aducanumab?

The rumor I heard two weeks ago was that it will be a few months before we hear anything from the FDA on approving Biogen's application for approval of aducanumab, but I don't know exactly what that means.  Is that when they will begin their work, or is that when we should expect a conclusion?

In any event, we have just learned that they will at least begin their work very soon -- November 6.  This will include, among other things, public hearings.  This is what I learned from this article.

Aducanumab is not a cure for Alzheimer's disease, but, if it lives up to expectations, it is a major breakthrough that can give a measure of relief to many families and to the healthcare and elder care systems. 

You are invited...

This Thursday, October 8, I will be speaking at the Alzheimer's Association Washington State Community Forum about my experience with Alzheimer's disease.  It's a Zoom meeting, so you don't need to be in Seattle, or even Washington State, to participate -- anyone can join.  And it's free.  If you're interested, you can register here.  It's at 2:00 p.m. Pacific Time, 5:00 p.m. Eastern Time, or 11:00 a.m Hawaiian Time.

 

Conference second day and the latest research update

I attended the second day of the conference, Collaborating for a Dementia-Friendly Washington, on Wednesday.  My part was to participate on a panel  of ten thought leaders, focusing on the major takeaways from the conference.  My takeaway was the utility of the toolkit that the Dementia-Friendly America organization has created for communities to use in understanding their situation with respect to livability of their communities for people with dementia.  It is a very rich and valuable resource.

The week before, I attended a webinar with Maria C. Carrillo, Chief Science Officer of the Alzheimer's Association in which she reviewed the current state of affairs in Alzheimer's research.  Here are a few highlights and interesting statements that I noted:   

• We don't know when the FDA will act on Biogen's request for approval of aducanumab, but there is some thought this may happen in March 2021.
• Aducanumab doesn't cure Alzheimer's disease, but it does appear to slow its progress.  What is significant about it is that it is the first medication that actually addresses the disease process.  Earlier medications, such as donepezil, may temporarily improve cognitive function, but they only treat symptoms.
• If aducanumab lives up to it's potential and even somewhat slows the progress of Alzheimer's disease, it could still significantly reduce the load of dementia patients on the healthcare system. 
  
• Thirty percent of dementia cases are mixed dementia, meaning that more than one cause is at work.
• Knowing what mix of causes is at work in a case of dementia will influence the treatment plan.  Therefore, there has been important work on several new types of PET scans that can more clearly distinguish which mechanisms are at work.  For this reason, the Alzheimer's Association is promoting the idea that Medicare should begin covering PET scans.
• As we've discussed previously, very sensitive blood tests for Alzheimer's disease are nearing approval.  This is very significant, because they will make it easier to identify per-clinical cases and thereby accelerate drug trials.  They are currently looking to recruit about 3,000 test subjects.
  
• There are currently 121 drug candidates involved in 136 trials in progress.  43% of these involve re-purposing previously approved drugs.
• As we noted before, there is a correlation between flu shots and reduced incidence of Alzheimer's disease.  No one knows why.  It may simply be that people who get flu shots tend to be people who live a healthier lifestyle.
  
• More work is needed to investigate Alzheimer's disease in non-white populations.  In the U.S., the disease incidence and progression is different among African American and Hispanic populations.  Much of the research to date has focused on Europeans and Americans of European ancestry.
• The current goal is the have a cure for Alzheimer's disease by 2025.