The theme of the Clinical Trials on Alzheimer’s Disease (CTAD) conference asked a question: Therapeutic Trials in AD: A New Hope for 2022? The answer, I am happy to report, is yes! This year’s conference was different than the 13 previous conferences — and I say that from the experience of having attended them all.
This year was notable for the number of clinical trials reporting results and the preview of many more expected to report out soon. Clinical research is a long game. What we are seeing now is the result of years of dedicated and diligent work by researchers across the globe. It isn’t just the quantity of research that matters, but the quality, and that was clearly evident too.
CTAD 2021 demonstrated how much Alzheimer’s research has matured. Just four or five years ago the research presented was nearly exclusively around abnormal amyloid and tau protein build up in the brain. It’s gratifying to see a much broader perspective taking hold, with trials at this year’s conference reporting on a wide range of novel and repurposed drugs targeting the many biology of aging factors implicated in Alzheimer’s, including inflammation, metabolic function, synaptic activity and more.
In just one example, ADDF-funded researcher Dr. Miranda Orr of Wake Forest discussed her work targeting so called “zombie cells” in the brain, which proliferate with aging. The cells have found a way to avoid the natural death cycle and instead they linger on, releasing toxins that damage nearby healthy cells. Her eagerly anticipated phase 2 study is testing a combination of two repurposed drugs that deactivate the internal programs in these zombie cells so they can go through their natural death process. Her phase 2 trial is enrolling adults 65 years and older with mild cognitive impairment at three different sites in the United and hopes to replicate earlier finding where the damaged cells were shut down and cognition was stabilized.
A reoccurring theme this year was the invaluable role of biomarkers in furthering Alzheimer’s research and the promise that one day soon they will be a vital part of day-to-day patient management. One blood test is already there. Data presented at CTAD confirmed that the PrecivityAD™ blood test, which received early funding from the ADDF, is 81% accurate in predicting the level of amyloid in the brain. The test’s effectiveness is evidenced by the fact that it was just chosen as tool to screen participants for the AHEAD study, a 75-site clinical trial funded partly by the National Institutes of Health that is testing an investigational treatment to delay memory loss before Alzheimer’s symptoms even begin. The test is currently on the market and available to physicians for their patients in 49 states, with New York expected to approve soon.
I talked about all of this and more with Dr. Jeffrey Cummings, Director of the Chambers-Grundy Center for Transformative Neuroscience at the University of Nevada, Las Vegas. Dr. Cummings is a world-renowned Alzheimer’s researcher and clinical trial expert.
We are both incredibly excited about the direction of Alzheimer’s research and optimistic about the many potential new treatments in development. In addition to discussing results and the promise of individual trials, Dr. Cummings and I also discussed two special sessions led by the ADDF at this year’s meeting.
In the first, we discussed the promise and challenges of repurposed drugs, which are already approved to treat other illnesses and are now being tested in Alzheimer’s. The session featured three ADDF-funded researchers.
- Ana Pereira at the Icahn School of Medicine in New York is repurposing an ALS (Lou Gehrig’s disease) drug called riluzole that modulates a neurotransmitter in the brain called glutamate.
- Giacomo Koch at the Saint Lucia Foundation in Rome is repurposing a Parkinson’s treatment called rotigotine that acts on dopamine transmission in the brain.
- Michela Gallagher of AgeneBio is evaluating a novel extended-release formulation of anti-epilepsy drug levetiracetam, which targets overactivity in a part of the brain that has a major role in learning and memory.
The upside of repurposed drugs like these is that the early research—animal testing and assessing drug safety in humans—is already done, giving researchers a head start. The challenge is it’s often difficult to attract the tens of millions of dollars in funding needed to bring these drugs to market.
Drs. Pereira, Koch and Gallagher discussed some of the innovative ways they’re approaching the challenge. This includes developing new doses and formulations that may yield new intellectual property, creating new biotech firms that can attract venture funding and take risks that large pharma companies cannot, and working more closely with the FDA on streamlining trial designs and incentivizing development of these potentially groundbreaking treatments.
In the second, we discussed exploratory trials. These phase 2a trials often provide the first signal for whether a drug is working against Alzheimer’s symptoms and, thanks to biomarkers, whether it is engaging with its intended target to potentially alter the course of the disease.
The panel featured experts from academia and pharma, as well as a statistician who discussed ways to maximize the design of these seminal trials, which are used to determine whether a drug moves on to lengthy and costly FDA-regulatory enabling trials or if they are abandoned. Ensuring these decisions are made based on sound research will help the ADDF and the field overall to optimize deployment of resources.
The ADDF has been leading the way in exploratory trials, convening an expert panel to develop best practices for their design. The guidance was published in May of this year in the journal Neurology. It was particularly heartening to hear Dr. Cummings say during our chat that not only did he hear from several people that this was one of the best panels at CTAD, but that he also knows of many who have used the Neurology article to aid in their trial design decision making.
The information that came of out of this year’s CTAD conference reflects significant progress in Alzheimer’s research. I hope you join me in taking pride in ADDF’s role in bringing us to this point. Together, we will continue to do great things.