2018 was a special year for the ADDF and the Alzheimer's community. Researchers from all over the world have contributed to our understanding of neurodegenerative diseases. There was progress on every front ranging from a better understanding of Alzheimer's disease, new partnerships with donors, a renewed interest in the biotech community, and new discoveries about how prevention can delay the onset of Alzheimer's and related dementias.
I've highlighted the top five advances I believe have made a significant impact in accelerating drug discovery and development—bringing renewed hope to people living with Alzheimer's.
1. Biomarkers and Better Clinical Trial Design
I have always felt we needed to jump start the search for new biomarkers. My dream came true when philanthropist Bill Gates and ADDF's co-founder Leonard Lauder, along with other philanthropists, announced the Diagnostics Accelerator, which will provide more than $35 million in grants to researchers for novel biomarkers for early, effective detection of Alzheimer's disease and other dementias.
The Diagnostics Accelerator is a game changer for the prevention and treatment for Alzheimer's disease. The response to our request for proposals from the scientific community is overwhelming. We are currently evaluating close to 300 proposals from 27 countries on six continents.
Biomarkers are used to diagnose, monitor disease progression, and aid in the development of effective drugs. For cancer, there are many biomarkers, such as blood tests and imaging tests. In Alzheimer's, very few validated biomarkers exist, which not only hampers drug development but can result in patients being misdiagnosed.
The ADDF supported the first biomarker ever approved to diagnose Alzheimer's—the beta-amyloid PET scan—and we continue to invest in these critical tools. Biomarkers will make clinical trials more efficient and rigorous. They are also being used to enroll patients in trials directed to a specific target, as was done most recently by Biogen with its anti-beta amyloid vaccines. Ultimately, biomarkers can determine which therapies would be most effective for an individual.
An online opinion article I wrote for Scientific American, "We Need New Biomarkers for Alzheimer's Disease," generated great reader interest and is printed in the February issue of the magazine.
2. Finding Treatments Based on our Understanding of the Biology of Aging
Aging is the leading risk factor for Alzheimer's disease. Both aging and Alzheimer's disease are due to complex multifactorial causes. This means we need "multiple shots on goal" to discover effective drugs, and as in cancer, we will need multiple drugs addressing multiple targets to effectively treat the disease.
I was the senior author of a paper published in the journal Neurology that explored novel approaches that could slow or prevent Alzheimer's beyond the common amyloid theory. Precision medicine using combination therapy is likely needed for better treatment outcomes in Alzheimer's disease, just as it is for heart disease and cancer.
3. Phase 2 Trials Reporting
Most of the clinical trials the ADDF is supporting are in phase 2, which is the first time a drug is tested in patients for efficacy. Many of these trials will be reporting in the next several years.
Some of our researchers shared promising results of their phase 2 studies at our 19th International Conference on Alzheimer's Drug Discovery. Giacomo Koch, MD, PhD, of the Santa Lucia Foundation, presented his findings of the DOPAD trial that will inform the design of a larger study for rotigotine (currently approved for Parkinson’s disease and restless leg syndrome) as a potential cognitive enhancer for Alzheimer's disease.
Krista Lanctôt, PhD, of Sunnybrook Health Sciences Center in Toronto, Canada, reported that the use of synthetic cannabinoid nabilone significantly reduced agitation in patients with moderate to severe Alzheimer's disease.
4. Increased Investments and Interest from the Biotech Community
There has also been an increased interest in the field with the biotech community raising significant funds to support novel ideas. In the last eight years, many of the major pharmaceutical companies cut back or closed their research and development into neurodegenerative disorders due to failures of drugs under investigation in late-stage pipelines. But the sheer burden of unmet medical need for people with neurodegenerative illnesses, including Alzheimer's, makes it hard to ignore.
Some examples of recent investments in companies developing drugs with novel targets include San Francisco based biotechs, Denali Therapeutics and Alector. In December 2017 Denali raised $250 million in an IPO for drugs that are neuroprotective and target neuroinflammation, and in July 2018 Alector raised $133 million and is planning a $150 million IPO in early 2019 for drugs that target neuroinflammation. Other companies also raised significant amounts such as IFM Therapeutics for neuroinflammation drugs and Magnolia Neurosciences (PDF) for neuroprotective drugs. In addition, although Pfizer closed its neuroscience division, Pfizer Ventures announced it would invest at least $150 million in promising early-stage neuroscience companies.
The ADDF is also providing funding in this positive environment to support novel ideas in early-stage companies so that they can leverage promising results to raise additional capital. One of our portfolio companies, Tetra Discovery Partners, is developing a drug that can bolster neuronal connections to improve learning and memory. The ADDF provided funding for an early clinical trial testing the drug for safety. Tetra raised $40 million from the pharmaceutical company Shiongi Inc. for a larger clinical trial in Alzheimer's patients. Similarly, the ADDF provided early funding to AgeneBio and Cognition Therapeutics, both of which have raised additional money from the National Institutes of Health for large clinical trials.
5. Prevention
2018 was a sea change in how we look at prevention. We now have scientific evidence that supports a healthy lifestyle to help reduce risk of getting Alzheimer's and dementia. Researchers in Finland reported that lifestyle changes improved cognitive function and memory in older people with APOE4, a genetic risk factor for Alzheimer's disease. And preliminary reports of the results of the SPRINT-MIND study, found that nondiabetic adults with increased risk for cardiovascular disease may reduce their risk of mild cognitive impairment (MCI) and the combined risk of MCI and dementia by reducing their blood pressure.
Richard S. Isaacson, MD, Director, Alzheimer's Prevention Clinic, Weill Cornell Medicine, published a paper last January in Frontiers of Aging Neuroscience, discussing six body mechanisms involved in Alzheimer's disease that offer promising targets for risk-reducing interventions. In November he published details on a comprehensive Alzheimer's risk reduction program and guidelines to personalize Alzheimer's risk management.
In an ADDF-funded study, Dr. Isaacson is collaborating with the ADDF's Cognitive Vitality program to build and test web-based brain health lessons in two randomized controlled trials—one for the lay public and another for healthcare professionals. His web-based, educational portal, Alzheimer's Universe, has educated 1.2 million people in 56 countries.
I have never been as optimistic as I am today that these advances will result in safe and effective drugs for the prevention and treatment of Alzheimer's disease. I am proud of the ADDF's leadership in the field and look forward to exciting developments in the year ahead.
Howard Fillit, MD is the Founding Executive Director and Chief Science Officer at the ADDF.