Alzheimer’s
Why I Work in Biotech Investing
Alzheimer's Disease is personal for me. When I was young, my grandmother, Rita Clements ("Gran Rita") was diagnosed with Alzheimer's Disease ("AD"), and eventually passed away in 2018. My family and I witnessed her progression of this horrific condition, and the emotional toll was high. Our family is blessed to have had the resources for extensive care and support options as Gran Rita battled Alzheimer's, but I am well aware that most families across the world are not so lucky.
As all families with Alzheimer's patients experience, our family came to accept the reality that no cure exists for AD. We understood the inevitable would come to pass. Despite decades of scientific research and billions of dollars spent on clinical trials down the drain, no meaningful progress has been made. Yes, there is positive research that points to lifestyle changes that can make a positive impact on disease progression, but we have had no medical breakthroughs as a result of the significant time and resources invested.
This trend is frustrating, but I am an optimist by nature -- I believe a breakthrough is on the horizon. We may still need another decade of research, experimentation, and clinical trials, but there is an intersection of scientific forces that point toward positive progress and renewed opportunity to address this puzzling disease.
Carrying on a Legacy
My grandmother’s battle with AD is only a part of my motivation to support biomedical innovation. Gran Rita cared deeply about supporting biomedical research and healthcare throughout her life, which compounds my interest in healthcare and biotechnology. She was a fervent supporter of UT Southwestern in Dallas, and I hope to honor her legacy in whatever way I can.
My writing and social media posts for 8th Summit consistently feature my grandfather, Dick Bass, because Dick provided the initial inspiration for the name, 8th Summit. Gran Rita’s life and legacy are equally as inspiring to me but in different ways. Her life’s pursuits also exemplify many of the values that 8th Summit aims to showcase. Most of all, her commitment to serve Texas and Dallas in different ways inspires me to emulate her service in my life. In addition to her support for UT Southwestern in Dallas she served on the UT Board of Regents and as First Lady of Texas. I firmly believe that Gran Rita would be proud of my goals to carry on the legacy of her service, and I hope that I can play a small role in finding treatments, predictions, and cures for Alzheimer’s Disease. Although this problem may take decades longer to create viable solutions, I have faith that in my lifetime many people will not suffer the hopeless fate of AD.
False Hope or Progress?
New FDA drug approvals for Biogen’s Aducanumab in 2021 and more recently Eisai’s Lecanemab have received huge amounts of press, both positive and negative. The approval for Aducanumab was marred by controversy because of the uncertainty that the drug had meaningful efficacy in slowing the disease. Several FDA officials resigned in protest of the FDA’s regulatory process and approval for Aducanumab, and Medicare refused to cover the wildly expensive new drug (almost $30,000 per year). Many hospitals also refused to administer it.
The controversy arises because the efficacy of Aducanumab was limited at best, and side effects could be severe. Aducanumab is one of many drugs in development that target the amyloid-beta (“amyloid”) plaques that accumulate in patients with AD and dementia. For decades, scientists have hypothesized that amyloid is the primary culprit for the disease and that clearing the amyloid plaque should improve or reverse the conditions of AD. This “Amyloid Hypothesis” has proven to be unreliable with only mild improvements in patients after billions of dollars spent on clinical trials by Biogen, Eisai, Eli Lilly, Roche and other companies.
The Amyloid Hypothesis has even created a cadre of scientists that promote its scientific promise aggressively despite the uncertainty. Some are even accused of falsifying their data. To be fair, these scientists are in a difficult situation: they have spent decades of their lives and perhaps their entire career testing the Amyloid Hypothesis. And, this research has shown positive indicators and promise. But, the unrelenting focus on the Amyloid Hypothesis has sucked the vast majority of resources and capital for scientific labs and clinical trials that could have fueled progress for alternative therapeutic approaches. For example, it is much harder for a lab to receive NIH funding for an alternative approach since the NIH has dedicated so many resources and focus on the Amyloid Hypothesis over the years
Amyloid clearing drugs are proving to be a mediocre approach to slowing the progression of AD symptoms, but they may be great to have as a first line of defense. In order to halt or reverse Alzheimer’s progression, we will need to look to alternative theories and targets. Importantly, we will also need to identify individuals with high genetic risk developing AD much earlier in life, and attempt to implement behavioral, supplemental, and therapeutic modalities for preventing AD progression in the first place.
Genetic Testing
The incredible cost reduction in genetic sequencing now allows individuals to know their genetic makeups for a relatively affordable price. Companies like 23andMe and The DNA Company offer tests for certain genes or even Whole Genome Sequence (WGS) tests direct-to-consumer by collecting simple saliva or blood samples for a few hundred dollars. (For context, the cost of sequencing the first whole human genome was $2.7 billion dollars and took 13 years to complete from 1990 to 2003). Some people may fear the knowledge of knowing your genetic risks. Personally, I want to know, and I took a test from The DNA Company. I firmly believe that with the right mindset this knowledge can empower you.
Because of Gran Rita, I expected to carry genes that suggest an increased risk of Alzheimer’s. My hunch was correct. The most widely validated and studied gene connected to Alzheimer’s is the ApoE gene which codes for the ApoE protein. There are several different classifications for this gene and they are notated by three different alleles, e2, e3, and e4, and each person carries two copies of the gene, one from Mom one from Dad. The lowest risk group are those that carry two copies of the APOE e2 allele, which is denominated as “APOE e2/e2.” The highest risk group are those the carry two copies of the APOE e4 gene, “APOE e4/e4,” and this group has on average about a ten times higher chance of developing AD. My genetic makeup is ApoE e3/e4, which suggests about a 2 to 3 times greater AD risk. Importantly, these “elevated risks” do not guarantee you will get the disease. Importantly, many people with ApoE 4/4 never develop AD; your genes are not your destiny. These high-risk individuals who stay healthy may carry other neuroprotective genes or they live lifestyles that promote brain health.
Knowing my elevated risk gives me an unexpected sense of empowerment. Since I am only 25 years old, I now can be deliberate throughout my whole life in taking steps that may prevent AD. Over time, our knowledge of the genetic determinants and underlying biology of AD will only improve. Because of my known risk, I have a strong desire to track this progress and stay at the cutting-edge of promising approaches for preventing neurodegeneration. Later on in life, if my doctors and I ever do develop concern for cognitive impairment, my genetic make-up could qualify me for genetically-targeted therapeutics (“precision medicines”).
Novel Therapeutic Approaches
Dozens of companies are developing therapeutics for AD with emerging, novel approaches. I will need to write a more in-depth blog post in the future to cover the wide gamut of companies, but I will highlight one promising area of research and development: microglia and inflammation. A growing body of evidence is demonstrating a clear connection between inflammation in the brain as an important contributor to cognitive decline and conditions like AD. Specifically, scientists believe microglia are a the type of cells in the brain that could be targeted by therapies to reduce or prevent inflammation. Microglia function similar to immune cells within the brain and have the ability to clear inflammatory proteins and markers if working properly. One example of a company targeting microglia with strong clinical trial progress is Alector. Alector has several trials in the pipeline targeting various neurodegenerative conditions, including Alzheimer’s, and microglia genes are one of their targets. Only time will tell if these trials bear fruit (and most trials fail), but this is one example of a company with a radically different approach to the amyloid drugs that have dominated clinical trials in recent years.
Holding Out Hope
Although AD has been an immensely difficult disease to understand, these new lines of research and testing provide hope to me. Decades ago, most cancers were a death sentence, and we did not have the diagnostic tests to find cancers at early stages when chances of successful treatments are much more likely. Today, we have a high likelihood of curing many cancers with a panoply of therapeutic approaches to target cancer. Many of these therapeutics, utilize specific protein or genetic targets. These “targeted therapies” are becoming more and more common and drug approvals for these drugs will only accelerate. Most cancers are easier to treat than neurodegenerative diseases but still took hundreds of billions of dollars of investment in R&D. The progress may be slower, but I have confidence that with enough time and invested resources a similar trajectory of progress will come for AD.
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As I continue to learn and do my own research on cutting-edge research and innovative companies pushing for progress on Alzheimer’s, I will periodically share my findings. In the meantime, the memories of and inspiration from Gran Rita will fuel my drive to become a mover and shaker in the world of biotech, health, and wellness.
Disclosure: I mention several companies that have publicly traded stocks in this post. I am not a financial advisor, and none of these mentions are intended to be investment advice.