Landmark study will test Genentech drug for Alzheimer's prevention

A drug in development at Roche's Genentech unit is to be tested in a landmark study to see if it can prevent early-onset Alzheimer's in people who are genetically predisposed to develop the disease.

The five-year study is the first of its kind and will see if Genentech's crenezumab can actually prevent Alzheimer's disease from developing among the members of an extended family grouping in Colombia that carry the presenilin-1 (PSEN1) gene.

People with the PSEN1 mutation have a much greater tendency to produce amyloid beta, one of the constituents of the plaques that characterise Alzheimer's, and typically go on to develop the cognitive symptoms of Alzheimer's around the age of 45.

Genentech is collaborating with the Banner Alzheimer's Institute and the National Institutes of Health on the $100m Alzheimer's Prevention Initiative (API) study, which will last five years and enrol around 300 asymptomatic subjects who can be traced to a PSEN1-positive common ancestor. A small number of patients in the trial will be from the US.

"We will attempt in the study to prevent the build-up of plaques in the brains of patients, thereby hopefully preventing the cognitive decline that accompanies the disease," said Richard Scheller, executive vice president of research and early development at Genentech.

"This is the ultimate test of whether amyloid beta is the toxic substance that causes the disease; up to this point this is still a hypothesis that has not been proven," he added.

Crenezumab is thought to cross the blood brain barrier into the central nervous system, bind to amyloid beta and cause it to be removed from the brain via the cerebrospinal fluid before it can aggregate into plaques.

If effective in the PSEN1-posiitve population, the antibody could become a means of preventing symptom development among patients with other, more common forms of Alzheimer's, said Scheller.

The humanised monoclonal antibody - known as MABT5102A - is in two trials looking at its ability to affect the progression of symptoms in patients with mild-to-moderate Alzheimer's. Genentech licensed the drug from Swiss biopharma company AC Immune in 2006.