One of the great benefits of The Reserve is that we can tap into a wealth of resources—notably our Members—to help us investigate intellectual pursuits that run the spectrum of science, health, and technology. This September evening was a case in point. This time, the topic was Alzheimer’s Disease—specifically, we discussed the causes of the growing disease that’s expected to climb from 5.4 million cases in 2016 to 13.8 million in 2050.
The Pavilion was set up to seamlessly accommodate the entire evening—from the expert-driven panel discussion to the wine-paired dinner. Members arrived to a champagne reception before sitting down in one of the rows of chairs facing the panel. The long, wine glass-covered tables stretched behind us as a reminder of the dinner to follow. In total, about 75 Members were in attendance, and during dinner the panelists and several other experts mingled with us at the table to offer more insight and answer questions in a more intimate setting.
The discussion touched on how we can delay the onset of Alzheimer’s, possibly prevent it, as well as whether there’s going to be a cure in our lifetime. Member Pascal Levensohn who is the Managing Director of Dolby Family Ventures moderated the lively discussion. He said that his main considerations in putting together a panel was to include “three of the most recognized global experts on Alzheimer’s Disease—all of whom I’ve had the pleasure of working with directly through the Dolby family’s commitment to finding a cure for AD.”
Mr. Levensohn explained the pillared approach of the Dolby’s hybrid philanthropic and for-profit investing strategy to help further research and ultimately find a cure for this disease. While he noted that there may not be a single cure in our lifetime, that doesn’t mean there isn’t hope. The four pillars are: 1) supporting disease modifying therapeutic programs focusing on de-risking companies to get to partnership stage, 2) improving patient and family experience now with the Ray Dolby Brain Health Center, 3) investing in startups at intersection of digital and medicine, and 4) supporting political action and advocacy to increase research funding.
The panel was small, but mighty—with a trifecta of scientists and doctors with expertise that is esteemed worldwide.
Alireza Atri, MD, PhD, the Ray Dolby Endowed Chair in Brain Health Research at California Pacific Medical Center and visiting faculty at Harvard Medical School.
Lennart Mucke, MD, Director of the Gladstone Institute of Neurological Disease in San Francisco and professor of neuroscience at UCSF.
Howard Fillit, MD, founding Executive Director and Chief Science Officer of the Alzheimer’s Drug Discovery Foundation in New York.
The primer by Dr. Atri, who is one of the most experienced principal investigators of phase III clinical trials for Alzheimer’s drugs, set the stage for the night as he brought us up to speed on the disease—explaining what it is, why it’s growing at such a large rate, and how to identify it.
We were reminded that this disease can, and does, attack even the most brilliant. As Dr. Atri says, it’s an equal-opportunity disease with victims including Gene Wilder, Ronald Reagan, and Charlton Heston. Brilliant people aren’t spared, he says. Three overarching questions that we aimed to gain a better understanding were:
Is there one root cause of AD?
Dr. Mucke responded that, Alzheimer’s is complicated. It’s actually a series of related brain diseases that cause and accelerate neuronal cell death. People are susceptible due to genetic factors. They can also contract it as a long-term effect of traumatic brain injury, and they can also become susceptible from vascular and inflammatory conditions. None are very well understood aside from the genetic cause of early onset, which is less than 1% of the population. The riskiest known Alzheimer’s gene variant, apolipoprotein E-e4 (APOE-e4), is alarming because it’s so common—roughly 20% of the population carries the gene, but like high cholesterol for heart disease, it’s only an indicator of potentially striking later in life. This causal complexity means it is unlikely that any one specific drug will ever be able to successfully address the full scope of the disease.
What is the single most important thing we can do to prevent or delay the onset of AD?
The panelists stressed that the prevalence of AD is increasing as the population ages, and since we’re making great advances in cardiovascular disease and cancer, longevity is increasing. The current paradigm is that people come to doctors too late. In fact, Alzheimer’s develops 10–20 years before a patient shows symptoms. And one of the more promising aspects of curing the disease is early detection, as this can help delay the progression of AD. Abnormal protein accumulations (for example, amyloid plaques or tau tangles) ultimately cause dysfunction of synapses and trigger neuronal cell death. These abnormal protein accumulations can be seen through PET scans. If we can turn the main focus to finding it in the early stages, we might be able to intervene before there is widespread damage to the brain. Again, today this early detection can delay, but ultimately not to prevent, Alzheimer’s. Breakthroughs in medical imaging of brains are on the horizon that may significantly help non-invasive early detection.
Today, if you are diagnosed with AD, is there anything you can do to stop it from progressing?
Dr. Fillit gave hope for medicines that will someday lessen the decline or deliver a cure, but this is a complicated disease that’s relatively new. In his professional career (which started in the late ‘70s), Alzheimer’s went from being relatively unheard of to being acknowledged and widely studied, but we are still far from a cure. The genetic insights clearly identify targets at the root of the disease, and while there are some exciting drugs in the late stages of trials, there are still no drugs that cure or reverse the disease yet. While some medicines can improve or stabilize symptoms, patients ultimately decline. There’s no single magic bullet. Because of the multifactorial nature of the disease, treatment needs to be individualized with a combination of medications.