For the first time ever, an experimental drug is being tested to determine whether it can prevent Alzheimer’s disease in a population that has a 100% genetic predisposition for early onset of the disease. The study, to start next year, will be one of only a few being conducted to test prevention treatments for a genetically predestined disease.

The cohort is very unique: members of an extended family of about 5,000 people from the Antioquia region of Colombia who carry a gene that causes them to develop early-onset Alzheimer's, with some experiencing symptoms of memory loss in their mid-30s, and most developing the disease by age 45.

The drug is crenezumab, from Genentech. Crenezumab attacks the protein beta amyloid in the brain. Many now believe that the disease is caused by a steady buildup of the sticky substance over many years.

The Colombian family—whose Alzheimer’s is caused by a mutation of a gene called presenillin—has been studied before, but not in this way, said Carole Ho, group medical director for Genentech. She oversees the neurology therapeutic area for Genentech, which includes clinical development of crenezumab.

“There have been studies for over 30 years on this population involving, for instance, clinical progression,” she said. “But this is the first time they’ll be helping test an interventional therapy.”

The family has thousands of members, but the trial will seek to recruit only 300 of them—all over age 30 and symptom-free. The gene mutation they carry allows the cohort to stay small, said Ho.

“Can we prevent Alzheimer’s? What’s very unique is that this particular group of participants allows us to address this question, because we know with 100% certainty that they will go on to get the disease,” she said. “In a prevention trial in the general population, that would be impossible, as you don’t know who will develop Alzheimer’s and who won’t. You have to enroll far more patients to get this many who will develop the disease.”

Genentech’s crenezumab beat out 25 rival drugs for a chance to work with this very unique population. The drug was selected because, unlike many of its competitors, it does not cause brain swelling. Rivals included Pfizer and Johnson & Johnson’s bapineuzumab, and Eli Lilly’s solanezumab.

Banner Health, a nonprofit organization that runs a hospital chain, will lead the trial. Banner is contributing $15 million, but the trial also is backed by a $16 million grant from the U.S. Department of Health & Human Services, part of the government’s new National Alzheimer's Plan, of which a goal is to find an effective treatment or prevention by 2025.

The rest of an estimated $100 million in total costs will be paid by Genentech, owned by Roche Holding. The primary CRO for the trial is PRA.

The family in Colombia, said Ho, is “extremely excited” to participate.

“I am so moved by the dedication and the interest they have in controlling their own destiny and finding a cure for others,” she said. For many years, the family thought of their genetic predestination as a curse.

Alzheimer's is the most common disease causing dementia, affecting 35.6 million people worldwide. Without an effective treatment, the number of Americans with Alzheimer's, currently estimated at 5.4 million, is expected to reach more than 10 million by 2050. That, in turn, could cause healthcare costs related to the disease to soar to more than $1 trillion annually. The Obama administration plans to invest $50 million in new Alzheimer's research funding in fiscal 2012, followed by another $80 million in fiscal 2013.

If Genentech’s drug works for the Colombian family, can those results be extrapolated to populations not necessarily predestined to develop Alzheimer’s? Ho says yes.

“Although familial Alzheimer’s constitutes a very small percentage of the Alzheimer’s disease population, we do know the biochemical consequences are the same: increased amyloid deposition in the brain,” she said. “And if we can demonstrate that the drug has beneficial clinical consequences in this population, then we can demonstrate it relative to the general Alzheimer’s population.”

Deposits of beta amyloid in the brain have been studied for decades. Thus far, though, removal of the plaque deposits has not resulted in improvement of cognitive abilities in those with Alzheimer’s. Many believe this is because, to be effective, drugs that target beta amyloid must be given before the plaque builds up and symptoms surface. The trial in Colombia will allow researchers a chance to test this theory.

“What’s really exciting is this is an opportunity to see if we can gain data that would suggest we can shift the paradigm from controlling symptoms to preventing the disease entirely,” said Ho.

If the study begins on time, Ho said, interim data would be expected in four to five years.

-- Suz Redfearn