Milestones, and Miles of Stones

By Dale Bredesen, M.D., Chief Science Officer for Apollo Health

I am both thrilled and grateful to announce that our successful, precision medicine clinical trial has been published in the Journal of Alzheimer’s Disease. Three absolutely outstanding physicians — Dr. Ann Hathaway, Dr. Kat Toups, and Dr. Deborah Gordon — achieved improvement in 84% of the trial patients, who had MCI (mild cognitive impairment) or dementia. It took us 30 years to get here, but this latest milestone will ultimately create a paradigm shift in the way we evaluate, prevent, and treat neurodegenerative diseases such as Alzheimer’s, Lewy body disease, macular degeneration, and ALS (Lou Gehrig’s disease).  
 
It began in 1993, when we discovered a new type of receptor, which we dubbed a dependence receptor, and which causes cells without growth factors to commit suicide. Then in 2000, we found that the parent of the Alzheimer’s amyloid — called APP for amyloid precursor protein — is actually one of these suicide receptors, so of course we wondered whether that function may have something to do with Alzheimer’s disease. Then in 2006, we found that indeed, irrespective of amyloid, the suicide function of APP is critical for “Mouzheimer’s” transgenic mice to develop Alzheimer’s. This led us to ask whether we could find drugs that would switch APP from causing cell suicide to preventing cell suicide, but we found that many different pathways play into this “Alzheimer’s switch”— hormones, inflammatory molecules, trophic factors, nutrients, and others — and in the middle of this, the light bulb suddenly came on and we realized that the genetics, toxicology, microbiology, epidemiology —  indeed, everything reported in the over 150,000 papers published on Alzheimer’s — fit neatly into a model in which Alzheimer’s disease could be conceptualized as a network insufficiency, one that could potentially be corrected by identifying and addressing the many contributors.  
 
So in 2011 we proposed the first comprehensive trial to do just that — identify and address the many contributors in a personalized way. Our proposed trial was rejected as being multivariable instead of the expected single drug approach, so we started with case studies, publishing data from over 100 patients with documented improvement between 2014 and 2018. Finally we were approved for our clinical trial in 2019, and once again we saw amelioration time after time in those who followed the protocol. Now it’s time for a larger, randomized controlled trial, and that is ready to start later this summer.
 
Of course, at every step along the way there has been skepticism and criticism, from our concept of dependence receptors to our transgenic mice to our proof-of-concept trial. There will likely be more stones cast after our upcoming trial, as well. But with each and every patient in whom we see a reversal of cognitive decline, and re-engagement with their families, we know that the years of research and translation have been well worth it. Here’s to a world in which Alzheimer’s is a rare disease, just as it should be.