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Discovery & Development Drug Discovery, Bioprocessing - Upstream & Downstream

Advancements in the Fight Against Alzheimer's Disease

Credit: Author supplied

Alzheimer's disease (AD) has long posed a formidable challenge to the field of medical science. From 1990 to 2019, the occurrence of AD experienced a 147.95 percent surge and is now affecting 40 million people worldwide, with numbers expected to double every 20 years up to around 2050. 

At the center of AD investigations are two troublemakers: amyloid beta plaques and tau neurofibrillary tangles. These are thought to kickstart a series of problems including inflammation, oxidation, excitotoxicity, and tau hyperphosphorylation, all leading to cognitive decline. Current treatments aim to fix imbalances in the brain’s messengers to ease cognitive problems. Medicines such as donepezil, galantamine, and rivastigmine (called acetylcholinesterase inhibitors or AChEIs) help with a messenger called acetylcholine, while memantine deals with another messenger called glutamate, keeping things in check. But these therapies only provide temporary relief for symptoms without addressing the underlying progressive deterioration and demise of brain cells. 

A more recent breakthrough involves targeting beta-amyloid plaques using monoclonal antibodies, such as lecanemab (born from a collaboration between Eisai and Biogen). Lecanemab has been approved by the FDA and is under review by the EMA, and it marks a shift away from symptomatic therapies to a potential disease-modifying effect. The drug has been shown to slow cognitive decline by 25 to 35 percent, with a report in the Harvard Gazette saying it could spark optimism and hope in the AD field (despite a black box warning for safety concerns). Another monoclonal antibody in development, donanemab, is also showing promise for slowing cognitive decline. 

There’s also a lot of other fascinating research taking place. For example, researchers from the Perelman School of Medicine at the University of Pennsylvania discovered that 4-phenylbutyrate (PBA) effectively reversed disease signs, including memory impairment, in an AD mouse model. Acting as a “chemical chaperone,” PBA inhibits protein accumulation, restoring normal protein regulation processes (proteostasis) in the brains of mice. The treatment significantly improved cognitive performance, even when administered late in the disease course. Notably, PBA is already approved by the FDA for an unrelated metabolic disorder. 

Researchers are also exploring prevention strategies. Research on dietary supplements indicates varying impacts of vitamins B6, B12, folates, E, C, and D for AD prevention. Red wine, glucosamine, omega-3, omega-6, antioxidants, and plant metabolites are just some potential avenues being researched to help protect the brain. Flavonoids, resveratrol, luteolin, and a Mediterranean diet also emerge as promising contributors. 

Outside of academia, the Critical Path for Alzheimer's Disease consortium aims to accelerate treatment development by fostering collaboration among pharmaceutical companies, nonprofit foundations, and government advisers. By sharing data from clinical trials and establishing data standards, researchers hope to expedite the discovery of more effective therapies for AD. As of May 2023, as indicated by a report from the Alzheimer's Association Journal, there were 187 trials underway to assess 141 drugs.

Accelerating research and clinical development efforts is crucial for alleviating the burden of Alzheimer’s. We need to improve trial design and infrastructure, use disease registries for rapid enrollment, employ validated biomarkers, and foster collaboration among all stakeholders. Increasing awareness, securing funding, promoting data sharing, and enhancing understanding of Alzheimer’s biology are also vital for drug development. As these plans unfold, momentum will build, bringing us closer to achieving our goals.

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About the Author
Mallikarjun Chityala

CEO, Fitabeo, UK

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