Howard Fillit, MD, the founding executive director and chief science officer at the Alzheimer’s Drug Discovery Foundation, sat with Moonshot for Life to discuss the state of Alzheimer’s research (AD). The Alzheimer’s Drug Discovery Foundation (ADDF) was founded in 1998 with a singular mission – find and fund the best ideas to prevent and treat Alzheimer’s. “Back then there wasn’t much in the drug pipeline for this disease. We had to change that, and we have,” says Dr. Fillit.

Dr. Fillit: We are in the business of developing drugs for Alzheimer’s disease and related dementias. We have three primary efforts: biomarkers, development of new treatments and treatments for prevention. So far, we have deployed about a hundred fifteen million dollars to about 590 drug development programs in 18 countries. Part of our operating principle is to invest in biotechnology companies. We have invested in almost a hundred biotechnology programs around the world in the last 20 years.

What’s your vision on how Alzheimer’s will be treated in the future? 

Dr. Fillit: I  have been focusing on Alzheimer’s for 40 years now and it is really amazing to me how we have evolved from the days when nobody had heard about Alzheimer’s to today where a lot of effort is going on in Alzheimer’s disease. I do think we are going to have new drugs in the near future, in 5 years from now. It will be the first of many new drugs that will come on the market. The other thing is we have learned a lot about lifestyle and medical comorbidities in terms of their contribution to the risk of Alzheimer’s disease and how they can be managed better. And how management of risk can really delay the onset of Alzheimer’s disease. There is some really good research about that. Studies have shown that prevention is possible to delay the onset of Alzheimer’s disease, with better lifestyle, exercise, diet, managing hypertension and diabetes.

Where is the science going at the moment? What are researchers focused on?

Dr. Fillit: There has been a large focus on beta amyloid as a target and some focus on tau as a target. This has been  mostly in clinical development in big pharma. We haven’t as an organization funded any beta amyloid projects for almost ten years now. We are funding targets, such as neuroprotection, neuroinflammation, vascular disease, epigenetics, mitochondrial energy failure, that are novel and are related to aging, which is the leading risk factor for Alzheimer’s disease.We are funding novel targets related to aging which is the leading risk factor for #Alzheimers says @a_hfillit @TheADDF Click To Tweet

Do you think they will lead to cures?

Dr. Fillit: Alzheimer’s disease is a multifactorial disease and it’s becoming clear that it’s more of a generic term for the pathology. Every person has some different pathology. We are going to a world of precision medicine where biomarkers will identify subtypes of people with Alzheimer’s and then we will tailor drugs to that specific subtype.

What are the key challenges that need to be addressed to get to that point?

Dr. Fillit: We really learned how to do trials much better. The ADDF contributed to the development of the first diagnostic test approved by the FDA and EMA for Alzheimer’s, AMYVID™. And now there is going to be tau imaging scans, other kinds of imaging scans. With Bill Gates and others, we have created the Diagnostics Accelerator, one of the primary purposes is to develop blood tests, blood biomarkers that could not only be used in the clinic to identify patients, but like the amyloid PET scans, imaging scans that can be used in clinical trials for the inclusion of patients and for monitoring the efficacy of therapy. But the biggest problem we have right now in clinical trials for Alzheimer’s, like in some other disease states like cancer, is recruitment of patients and enrolling patients. Less than 5% of Alzheimer’s patients are currently enrolled in clinical trials and it makes the clinical trials very long and very expensive.

ADDF recently announced a new research initiative as part of its Diagnostics Accelerator with expanded funding from  Bill Gates and Jeff and MacKenzie Bezos to fast-track the development of new diagnostic tools, such as blood tests and digital mobile phone apps, for the early detection of Alzheimer’s.With @BillGates and other philanthropists we have created the Diagnostics Accelerator to develop #diagnostics that can improve #clinicaltrials says @a_hfillit @TheADDF Click To Tweet

There have been a couple of failures over the last years, how do you look at them?

Dr. Fillit: There have been a lot of failures, but I think we had to learn how to do clinical trials better. A lot of the failures might have been due to the fact that we weren’t doing the clinical trials right. We weren’t showing target engagement with our drugs in Phase II. We weren’t using biomarkers to enroll and monitor patients in proper waysin ways that we can do now, that we couldn’t do in the past. I think studies that can use biomarkers will have a much greater success rate.

What’s the ambition of the ADDF, what do you want to achieve?

Dr. Fillit: I would like to help bring the first non-amyloid treatment to market. I would like to have ADDF  contribute to that. Right now, we are funding 33 clinical trials and I am hoping that at least one or two of those will be successful and will lead to approval around the world. It will be one of the first, even if it is a modest effect, it will break open the field and lead to one of the first new treatments. We haven’t had a treatment approved since 2003. We will go for a new approval.

What’s the timeframe?

Dr. Fillit:  I think in five years we will have something.

I would like to help bring the first non-amyloid treatment to market. I would like to have ADDF contribute to that.

Howard Fillit, MDFounding Executive Director and Chief Science Officer Alzheimer’s Drug Discovery Foundation
Nicole Verbeeck

Nicole Verbeeck

Nicole Verbeeck is Founder and Editor-in-Chief of Moonshot for Life, covering medical innovation, storyfying progress in healthcare. She is also founder of Juneau Cayenne, a creative design, content and technology lab crafting innovative storytelling experiences for clients in healthcare and life sciences worldwide.

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