Howard Fillit, MD: Repurposing Therapies for Alzheimer Disease

DECEMBER 07, 2017
Matt Hoffman
Howard Fillit, MD, the founding executive director and chief scientific officer at the Alzheimer's Drug Discovery Foundation, sat with MD Magazine to discuss the state of therapies for Alzheimer Disease (AD). The foundation helps fund clinical trials for therapies that are often too much of an investment risk for funding to be acquired. 

He stressed the pressing need for repurposed drugs, such as those that have been re-utilized for cancer and migraine therapies, that can be used to help patients with AD sooner rather than later. Despite multiple advancements having been made and some promising therapies in the pipeline this year, Fillit acknowledged that none are a cure for the neurodegenerative condition, and therapies that slow the progression of cognitive impairment are becoming more and more important.

Howard Fillit, MD, founding executive director and chief scientific officer of the Alzheimer's Drug Discovery Foundation:
What we need - like in cancer, like in diabetes, like in hypertension, like in HIV/AIDS - we're going to need combination therapy because the way this disease evolves is multifactorial. You have inflammation, epigenetic changes, neuronal energy failure, mitochondrial dysfunction, hypoxia and ischemia from microvascular disease, protein chaperone misfolding and failure, so we are going to need a combination of drugs to attack this disease, just like in cancer.

There is a lot of excitement now because there are over 250 clinical trials testing 126 drugs, and our foundation just put out a clinical trials report (which is available on our website) which delineates all of these drugs. It is amazing because when I started in the field in 1980, there were no drugs in clinical trials. Now we have got 126, and our foundation has supported about 25% of those, which is amazing. There are drugs in clinical trials that are anti-inflammatory now that are epigenetics, and we're supporting a number of biotech companies that are doing this.

It is actually a really exciting time to be in drug development and drug discovery for Alzheimer's because there are so many targets that we know about now from the biology that could be the focus of drugs - and we're testing a lot of them, including 17 repurposing drugs. In other words, taking drugs that are on the market and testing them. They might be on the market for other neurodegenerative diseases, like ALS and Parkinson's, and are disease-modifying drugs, [and we are] repurposing them and testing them in Alzheimer's patients. A number of them will report out in the next year or 2.

The advantage of repurposing is that if these trials are positive and the drugs are shown to be safe, then the next day I can prescribe these drugs off-label for my patients. I do not have to wait for FDA clearance. The big opportunity when you discover a repurposing drug that works is that then we can go back and do new chemistry, create new chemical entities, get new indications for unique drugs, and build the space because we have a proof-of-concept. 

For example, in ALS, we are repurposing riluzole, which is the only drug that has really ever been shown to slow the course of ALS. We're repurposing that for people with Alzheimer's disease right now. I expect that trial will wrap up in about 2 years, so that is pretty quick. We are going to have an answer [soon], unlike when new chemical entities have to go through a regulatory environment that takes 12 to 15 years. Once these trials come out, it opens up a new area, but the drugs can be used off-label immediately.

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