In the largest planned study to examine the effects of a new Alzheimer's Disease (AD) treatment is underway. It will involve 40 sites across the country. Some of the notable sites include Yale University School of Medicine; Northwestern University; the University of California San Diego; University of Michigan, Ann Arbor; University of Kentucky; University of Pittsburgh; and Johns Hopkins University, to name a few. The clinical studies are being coordinated through UC San Diego's Alzheimer's Disease Cooperative Study (ADCS) headed by Dr. Howard Feldman, MD.
Photo source: Pixabay.com
The official name of this colossal undertaking is T2 Protect AD and is still accepting volunteers. To sign up you can go to www.t2protect.org. The project should take a year for each participant, or, as Dr. Feldman told KPBS News, “We are examining for benefits in cognitive function and thinking and memory over the course of one year.” He went on to say, " We’re aiming to achieve somewhere of about a 40 percent reduction in what would typically happen to a person over this period of time.”
The drug being tested is a compound called toriluzole (BHV-4157), developed by Biohaven Pharmaceuticals. Toriluzole was developed by Biohaven's glutamate platform. It is designed to balance the glutamate system through glutamate transporter modulation. One school of thought suggests that AD, as well as other neurodegenerative diseases, such as ALS, is due to too much glutamate in the synapse. Because this can cause excitotoxicity (which kills neurons), the idea is that by restoring the glutamate balance you can slow or even reverse symptoms of AD.
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Preclinical investigations have lent credence to the idea that excess glutamate could cause some if not all of the symptoms of AD. For instance, one study showed that excess glutamate in the synapse, due to ineffective glutamate transporters (GLT-1) in genetically engineered mice, produced AD-like symptoms. Another study revealed that restoring glutamate transporters in mouse models of AD significantly improved cognitive functions, restored synaptic integrity, and reduced amyloid plaques.
Previous attempts based on different scientific hypotheses for the etiology, progression, and fatality of AD have helped, but not cured, AD patients. Cholinesterase (the enzyme that breaks down acetylcholine) inhibitors are used based on the theory that AD is due to deficits in the cholinergic system. Vitamin E supplements, exercise, and cognitive stimulation have also been used to slow cognitive decline in AD patients. Biohaven has recently presented their rationale for their Phase II / Phase III clinical trials at the 11th conference of Clinical Trials on Alzheimer's Disease (CTAD). If these studies prove promising we may have a new weapon in our arsenal against AD.
Below is a very brief video going into more depth about how glutamate neurons could become excitotoxic. The video focuses on stroke, which is the definite cause of glutamate excitotoxicity in this case. Scientists are not sure what leads to glutamate excitotoxicity in AD, but the process would essentially lead to the same consequences.
Video source: YouTube.com