Despite the vast population Alzheimer’s disease (AD) affects each year and the urgency surrounding the disease, no new drugs have been approved by the FDA in 16 years. In addition to that, only five medical treatments have ever been approved for AD, and these treatments only act to control symptoms rather than change the course of the disease. The lack of success in AD drug development has infused scepticism in the field. Voices can be heard saying to abandon the amyloid hypothesis and focus on novel approaches, try combination therapies, work on early diagnosis or build new models for drug development.
This recent scientific publication shows the latest developments in the AD drug pipeline as of 2019. There are a total of 132 agents in clinical trials listed on clinicaltrials.gov with 96 of them focusing on disease modification. The article presents the drugs at different clinical phases (1-3). In brief, phase one focuses on testing safety on a small number of patients with a small dose of the drug. Phase two is designed to test the efficacy and side effects with therapeutic doses, (proof-of-concept), whereas phase three tests the drugs efficacy and effectiveness on a larger sample of patients. Amyloid plaques and Tau are still the main targets in clinical trials, with Amyloids as the dominant target in phase two and phase three trials. The drugs presented are classified as biological therapies (antibodies, proteins, stem cells etc) and small molecules (low weight organic compounds). Mechanisms of action presented are for e.g. amyloids plaques reduction, anti-inflammation, metabolic interventions, neuronal regeneration and protection, and interactions with neurotransmitter signaling. A different category, devices, is also discussed; such as implantable electrodes for neurostimulation with electrical currents.
Bear in mind that all clinical trial for disease modification of AD so far has failed approval by the FDA. However the next ten years of AD research will be exciting. All we know is that we need to be innovative and persistent. What would be the first therapy that will turn the course of the disease, alleviate suffering for almost 30 million people worldwide and millions more that will acquire AD?