After an announcement by federal officials approving clinical trials for the drug Crenezumab, researchers searching for a way to treat Alzheimer's Disease are gearing up for a rare study that will allow them to test a therapy for a genetically predestined disease -- before its onset.
"This is really incredible," said UC Santa Barbara neuroscientist Ken Kosik, who is the Harriman Professor of Neuroscience Research in the Department of Molecular, Cellular & Developmental Biology, and co-director of UCSB's Neuroscience Research Institute. He, along with several other Alzheimer's experts in the United States and Colombia, will be conducting the five-year, $100 million study, starting early next year.
The scientists will be drawing their study participants from a large family in Medell-n, Colombia. It's a family of about 3,000, with the unfortunate distinction of coming down with the disease early in life - onset begins at around 49 years of age. Unlike the kind of Alzheimer's that strikes late in life, this particular form has been traced to a specific genetic mutation.
"Almost everybody, if they have the mutation, gets the disease like clockwork," said Kosik, who first met with members of the family in the early 1990's, just after starting his work with Alzheimer's as an assistant professor at Harvard University. His interests led him to Bogot-, where he met Francisco Lopera, the Colombian neurologist who told him of the family, and who is another lead researcher on the study.
At the time, there was the interest in starting treatment and research, but the country was in upheaval, caught between political insurgents, drug cartels, and internal armed conflicts. Pharmaceutical companies were reluctant to invest or participate in any trials.
Two decades later, not only has turmoil in the country decreased, but the thinking toward treatment of Alzheimer's Disease has shifted from cure to prevention, paving the way for studies such as this one.
"When the brain is severely damaged with full-blown Alzheimer's disease, it's very hard to treat. There's already been a lot of damage and you can't replace the neurons that have died," said Kosik.
About two years ago, Kosik received a call to do this study from colleague Eric Reiman, executive director of the Banner Alzheimer's Institute in Phoenix and another lead researcher. At that time, several Phase 3 trials on what was hoped to be a viable treatment for sufferers of the disease had failed, forcing the neuroscientists to rethink their approach.
What is unique about this opportunity, said Kosik, is that the population being studied is a relatively homogenous group. Family members have the same genetic mutation, the same rural background, similar diets, and activities.
"They have said over and over that this disease has been such a burden to them, that they want to participate in a clinical trial," Kosik said.
The study involves testing candidates for the genetic mutation, taking a record of baseline conditions, administering either the medication or a placebo over a period of time, and monitoring the subjects' progress. In this double-blind trial, neither the subjects nor the investigators will know which subjects have the mutation, or which ones receive the drug or the placebo. A third party will handle that information.
Additionally, a group of participants that don't have the mutation will be included in the mix, and will receive the placebo -- a measure taken to ensure that the family members in the study don't know whether or not they have the mutation. In total, 300 members of the family will be participating in the first phase of the study.
Kosik, who has been concentrating on the genetic and ethical side of the research, said he agonized over whether the family members should be told of their genetic status.