Ongoing Phase III trials for AD

Contributed by: Michael Rafii, M.D., Ph.D - Director of the Memory Disorders Clinic at the University of California, San Diego. ______________________________________

Despite the recent stoppage of the semagacestat trial and the negative findings from the Dimebon study, there still remains a frenzy of activity searching for a disease modifying drug for AD. There are currently three large phase III trials being conducted for mild-to-moderate AD, and more about to get underway:

Bapineuzumab is a humanized, monoclonal, anti–beta-amyloid antibody. It is designed to bind to and remove the beta-amyloid peptide that accumulates in the brains of those with Alzheimer’s. This study uses an approach called “passive immunization” in which subjects are immunized with antibodies to beta-amyloid.

On the market for more than 25 years as a treatment for autoimmune diseases, IVIg contains antibodies that bind to the beta-amyloid aggregates many believe are central to cognitive decline of Alzheimer’s.

Solanezumab (LY-2062430):
Solanezumab is a beta-amyloid antibody designed to bind to and remove the beta-amyloid protein that accumulates in the brains of those with Alzheimer’s. More specifically, it binds to soluble beta-amyloid and may pull the beta-amyloid away from the brain to be cleared through the blood.

In addition, a Phase III trial of Resveretrol in mild-to-moderate AD will soon begin. Resveratrol is a compound in grapes and wine. While levels of resveratrol in wine varies, it is generally more abundant in red grapes and red wine. Resveratrol intake has demonstrated in vivo protective properties against multiple illnesses, including cancer, cardiovascular disease, and ischemia, and was also found to confer resistance to stress and to extend life span. It has been demonstrated in small studies to have some positive effects in AD. Resveratrol has been shown to lower the levels of secreted and intracellular amyloid-beta (Abeta) peptides produced from different cell lines by promoting intracellular degradation of Abeta. It has been shown to promote neuronal survival.

To sum up, beta-amyloid is still the target for most Alzheimer's therapies. We are learning that soluble beta-amyloid, not amyloid plaque, is most likely causing brain cell destruction. I think each trial has a very good chance of showing some benefit. Namely, in each of these trials (perhaps with the exception of resveretrol), soluble amyloid is the target, and the immune system is being used to target beta-amyloid. The big question is whether treatment is initiated early enough in the course of the disease to limit how much damage soluble beta-amyloid is causing.

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1 comment :

  1. Is there also an open trial for poly-therapy with Dimebon and Aricept? If so, what is the status?