WAM recently received a question from a reader about the latest on Alzheimer’s drug research. So we turned to the man who knows this field better than anyone, Dr. Howard Fillit, Founding Executive Director and Chief Science Officer of the Alzheimer’s Drug Discovery Foundation (ADDF), and a member of WAM’s Scientific Advisory Council. His question came via video from Stephanie Devaney. Read Dr. Fillit’s answer below!
Stephanie Devaney: I’m just wondering about any updates on Biogen’s TANGO trials for Gosuranemab and ask if you all have heard anything specifically regarding any of the outcomes or any data that’s been released? It’s been a wonderful drug for my brother-in-law, and just wondering if it’s another hopeful on the horizon in addition to Biogen’s Aducanumab?
Dr. Fillit: There is a lot of interest in anti-tau antibodies, which work by removing tau from brain synapses and keep it from spreading. As the disease progresses, tau jumps from synapse to synapse and we want to stop this. The investigational drug, called gosuranemab (BIIB092), is being studied in the TANGO trial in patients with early Alzheimer’s disease. The drug is designed to target the tau protein, which is one of the key proteins that build up in the brain of Alzheimer’s patients. Researchers are evaluating the investigational drug to see if it may help reduce the spread of tau in the brain—potentially slowing the progress of the disease. This trial is currently in phase 2, and has not reported results yet, but we look forward to seeing those.
WAM then had a few more questions for Dr. Fillit about other Alzheimer’s drugs making news.
WAM: There is a lot of talk about the potential for new Alzheimer’s drugs. You are so close to the research. Which do you feel holds the greatest promise? And how are they attacking the disease?
Dr. Fillit: This is a defining time for Alzheimer’s research with better diagnostics, a solid scientific understanding, and 120 drugs in clinical trials looking at novel treatments for Alzheimer’s disease.
This June an FDA decision is expected for Biogen’s aducanumab, which would be the first disease-modifying treatment to show that reduction in amyloid plaques in the brain slows cognitive decline in patients with early-stage Alzheimer’s and potentially helps them maintain their ability to complete activities of daily living. Whatever the final decision may be, the aducanumab clinical trial was a landmark trial that moved the field forward, as it was one of the first trials to use a biomarker test to enroll patients who had amyloid plaques in the brain, a hallmark of Alzheimer’s and the target of aducanumab. Biomarkers — from PET scans and CSF fluid tests to the recently-announced first ever blood test biomarker – reflect a new era in Alzheimer’s drug development.
The drug pipeline is more diverse today than it has ever been. While the primary focus of Alzheimer’s drug discovery over the past two decades has been the beta amyloid target, novel research approaches are gaining ground. At the Alzheimer’s Drug Discovery Foundation (ADDF), we have long believed that aging is the leading risk factor for Alzheimer’s, and as such, and it is likely new therapeutics for Alzheimer’s disease will come from an understanding of the effects of aging on the brain. We have continued to increase our support for the development of drugs that address the multitude of aging-related biological changes that may contribute to this complex disease. Today, the ADDF is funding 35 active clinical trials targeting novel mechanisms, aimed at neuroinflammation, genetics and epigenetics, neuroprotection, and metabolic and mitochondrial dysfunction, among other aging malfunctions.
Later this year we are expecting several promising phase 2 trials to report new data. There are a few trials I am particularly excited about, including one led by Dr. Frank Longo of Stanford University and the biotech PharmatrophiX, who has developed a drug, C-31, aimed at protecting brain cells from damage and halting the progression of Alzheimer’s. Another encouraging trial we are anticipating results from is led by Dr. Ana Pereira of the Icahn School of Medicine at Mount Sinai Hospital, exploring riluzole, an FDA-approved drug for ALS, for the potential treatment of Alzheimer’s disease. Riluzole works to modulate the age-related build-up of a neurotransmitter called glutamate, which can affect synapses and accelerate age-related cognitive decline.
Alzheimer’s is a complex disease. Our success in fighting it will likely involve combination therapy – an approach that’s standard of care in diseases of aging such as diabetes, heart disease and cancer. Combination therapy through precision medicine is ultimately the goal.
WAM: If someone is diagnosed today and doesn’t have a drug available that is effective, what do you advise that person to do in terms of lifestyle and/or therapeutic interventions?
Dr. Fillit: When I meet a newly diagnosed patient for the first time, I look at three key areas: healthy lifestyle, risk reduction and new therapeutics.
As the evidence mounts that personalized lifestyle interventions may improve cognitive functions and memory, particularly in people at risk for Alzheimer’s, it is never too early for all of us to start taking action to preserve our cognitive vitality. Make brain health a part of your overall healthcare routine by following a healthy lifestyle, including diet, exercise, sleep, reducing stress, and being socially engaged. Providing credible, science-based strategies to promote brain health and prevent Alzheimer’s disease is the focus of our Cognitive Vitality resource, where you can find more information on seven steps to help maintain your brain health.
Aside from living a healthy lifestyle, it is also important to reduce your risk for Alzheimer’s by avoiding smoking and excessive alcohol, managing medical co-morbidities/chronic illnesses, such as diabetes and hypertension, and treating depression. We recently reported on the latest finding from the Lancet Commission, which said targeting 12 risk factors throughout life may delay or prevent up to 40% of dementia cases.
Lastly, I often discuss exploring therapeutics with my patients – there are two types of drugs on the market that focus on enhancing memory and cognitive function. Cholinesterase inhibitors are modestly effective in treating the symptoms of Alzheimer’s, while memantine drugs help improve memory and cognitive function in people with moderate to severe dementia.
Another option is to consider participating in a clinical trial. Clinical trials are being conducted all over the world right now and need people in every stage of Alzheimer’s, as well as non-symptomatic aging population. Your participation can help us find a cure.
Howard Fillit, MD is the Founding Executive Director and Chief Science Officer, the Alzheimer’s Drug Discovery Foundation (ADDF) and is a Clinical Professor of Geriatric Medicine, Palliative Care and Neuroscience, The Icahn School of Medicine at Mount Sinai.
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