Scientists have chosen the first drugs that will be tested as part of a global clinical study to find ways to prevent Alzheimer’s disease. The news was announced Wednesday in a press release from Washington University in St. Louis, the home base for the research.
The trial will kick off early next year by testing three drugs, which each aim to stop Alzheimer’s in different ways. The study will look at people who have “inherited mutations” that lead to early-onset Alzheimer’s, and try to find out if the drugs can “prevent the loss of cognitive function.”
“This trial is the result of a groundbreaking collaboration between academic institutions, pharmaceutical companies and patient advocacy groups, with key support from regulatory groups,” principal investigator Dr. Randall Bateman, the Charles F. and Joanne Knight Distinguished Professor in Neurology at Washington University, said in a statement. “We are excited that this diverse portfolio of drugs and approaches will accelerate the discovery of an effective treatment for Alzheimer’s.”
The research will be done by the Dominantly Inherited Alzheimer’s Network Trials Unit (DIAN TU) at Washington University’ s medical school. This trials unit is supported by the DIAN, a National Institutes of Health-funded collaboration of world-leading Alzheimer’s research centers; the Alzheimer’s Association; and the DIAN Pharma Consortium, composed of 10 pharmaceutical companies that have been advising DIAN researchers on the planning of the trial.
Alzheimer’s researchers chose three investigational drugs from more than a dozen nominations submitted.
“Each drug has a unique approach to counter the toxic effects of amyloid beta, the main ingredient of brain plaques found in Alzheimer’s patients,” the school said. “Each also has passed earlier clinical trials that evaluated safety and effectiveness of the drugs and whether they engaged their targets in patients.”
The drugs that will be evaluated are, as described in the press release:
*Gantenerumab, an antibody made by Roche that binds to all forms of aggregated amyloid beta and helps remove them from the brain. Gantenerumab is currently in an international phase III trial known as SCarlet RoAD, started in 2010, that will test the drug’s ability to stop Alzheimer’s prior to dementia.
*Solanezumab, a monoclonal antibody in phase III clinical trials. Discovered and developed by Eli Lilly & Co., it binds to soluble forms of amyloid beta after they are produced, allowing amyloid beta to be cleared before it clumps together to form plaques.
The third drug selected for potential inclusion in the trial is a beta-secretase (BACE) inhibitor, a small molecule in Phase II clinical trials that was also discovered and developed by Lilly. BACE is theorized to work by reducing the amount of amyloid beta proteins produced, slowing the accumulation of plaques.
The trial is partially being funded by a $4.2 million grant from the Alzheimer’s Association. The study will involve 160 people who have inherited mutations that make it likely they will develop Alzheimer’s at a young age, from their 30s to 50s. The trial also will track 80 DIAN participants who did not inherit the Alzheimer’s mutations.
The participants with the mutations will be randomly assigned to receive one of three investigational drugs (75 percent chance) or a placebo (25 percent chance). Those without mutations also will receive a placebo.
“All of the experimental group’s subjects will be within 10 to 15 years of the anticipated age when symptoms of cognitive decline and dementia are expected to appear,” the press release said. “Earlier DIAN studies have shown that at this point in their lives, people who have Alzheimer’s mutations are likely to have biological indicators that show the disease is beginning in the brain, including evidence of brain plaques and changes in the blood and cerebrospinal fluid.”
Researchers will follow those indicators to learn if the new treatments slow or prevent the disease process. The trial’s first part will take two years, and will be extended if any of the drugs are effective.
The trial sites include the Charles F. and Joanne Knight Alzheimer’s Disease Research Center at Washington University, and other centers in North America, Europe, Australia and elsewhere in the world.