Drug Discovery – The Innovation Engine Powering Cures

Howard Fillit, M.D.

As the Chief Science Officer of the Alzheimer’s Drug Discovery Foundation (ADDF), I am often asked: what is drug discovery? It is the “innovation engine” that drives breakthroughs in treating diseases.

Diseases of the brain, such as Alzheimer’s, are complex. Though the cause of Alzheimer’s isn’t fully understood, scientists continue to uncover new processes that contribute to it. And each new finding into the cause of the disease represents a potential target for drugs to treat it – and an opportunity for innovation.

When the ADDF was founded in 1998, the pipeline of drugs in development for Alzheimer’s was limited. The few drugs being developed almost all focused on the same target, beta-amyloid. In Alzheimer’s, scientists think this protein misfolds and accumulates into toxic plaques. It was one of the earliest processes discovered in Alzheimer’s, so it makes sense that it was the first drug target pursued.

Now, we know a lot more. Inflammation, genes including APOE, epigenetics, oxidation, mitochondrial dysfunction and vascular issues are among the factors contributing to the development of Alzheimer’s disease. We also know that beta-amyloid isn’t the only misfolded protein damaging neurons – tau, TDP-43, and α-synuclein (e.g., Lewy bodies) are involved in Alzheimer’s and other neurodegenerative diseases. But major investments by pharmaceutical companies and others in Alzheimer’s drugs in clinical trials are still targeting beta-amyloid and, to a lesser extent, tau.

The ADDF pursues a different path. Our commitment to innovation leads us to fund new drug targets as they emerge, resulting in a more diverse pipeline of drugs. In 2001, we supported one of the earliest drug discovery programs targeting neuroinflammation by Dr. D. Martin Watterson at Northwestern University. Dr. Watterson went on to develop three potential Alzheimer’s drugs – MW 150, 151, and 189 – all of which are advancing to clinical trials.

A year before the ADDF funded Dr. Watterson, we invested in a pioneering idea for an Alzheimer’s treatment from Dr. Frank Longo, currently a professor at Stanford University. Dr. Longo had discovered a receptor on neurons that could help protect them from multiple kinds of damage, and he wanted to try to find compounds to activate it. This approach, now called “neuroprotection,” was entirely untested and therefore risky.

In drug research, risk is the enemy of innovation. Risk means you might fail, lose money or have to start over. For the ADDF, risk is an opportunity to learn. We have a staff of neuroscientists who dig into the available research to understand emerging targets and how drugs for them could (or could not) work. With Dr. Longo, we saw the opportunity to develop a drug that could change Alzheimer’s forever. Today, that drug is called LM11A-31 and it is being tested in Alzheimer’s patients in Phase 2 clinical trials. Time Magazine hailed it as “a radical new drug (that) could change old age.”

Drug discovery is risky, yes, but it’s where the most innovative ideas to conquer Alzheimer’s are born.

Thanks to the ADDF’s commitment to innovation, our generous donors, and federal funding, the drug pipeline in Alzheimer’s is robust, and effective treatments are in our sights. Click here to learn how you can support the ADDF’s important work.

Howard Fillit, M.D., is the Founding Executive Director and Chief Science Officer of the Alzheimer’s Drug Discovery Foundation. 

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Without continued support for health research, many of the most promising young scientists, their ideas and a myriad of potentially life-changing scientific breakthroughs will vanish into oblivion.
Paul Marinec, PhD; University of California San Francisco