Summary: Researchers are testing a preventive vaccine and an oral medication that aim to delay or stop Alzheimer’s disease in people with a genetic risk.
Source: Keck Medicine USC.
The Keck School of Medicine of USC launches a study exploring whether two different therapies can prevent a leading cause of death.
Researchers at the Keck School of Medicine of the University of Southern California (USC) have launched a major prevention trial addressing Alzheimer’s disease, the sixth-leading cause of death in the United States. The Generation Study brings together roughly 90 institutions across North America, Europe and Australia to evaluate whether a vaccine and an oral medication can prevent or delay the onset of Alzheimer’s in older adults who carry a genetic risk factor. More than 70 researchers at USC from diverse disciplines are contributing to this effort to prevent, treat and ultimately find a cure for the disease.
Instead of focusing on treatment after symptoms appear, this study emphasizes prevention, intervening years before clinical Alzheimer’s usually becomes evident. By testing therapies in adults who are cognitively normal but genetically predisposed, investigators hope to stop or significantly slow the disease’s progression before it begins.
“One of the challenges in Alzheimer’s drug development has been that many trials enroll people with advanced disease, when treatments rarely succeed,” says Lon Schneider, MD, the study’s lead investigator at Keck and professor of psychiatry, behavioral sciences and neurology. “By intervening 10 to 12 years before symptoms typically occur, we may have a better chance of preventing or delaying onset.”
Adults between the ages of 60 and 75 who are interested in participating are asked to undergo genetic testing for the apolipoprotein E4 (APOE4) gene, a well-established risk factor for Alzheimer’s disease. Approximately half of people with Alzheimer’s carry at least one copy of the APOE4 variant. About one-quarter of the general population carries one copy, and roughly two to three percent carry two copies—one inherited from each parent. This trial focuses on participants who carry two copies of APOE4, the group at highest genetic risk.
Qualified participants will be randomly assigned to one of four groups: an active vaccine, an active oral medication, a placebo vaccine or a placebo oral medication. Both active treatments target amyloid beta, the protein that forms the characteristic amyloid plaques found in the brains of people with Alzheimer’s. The vaccine is designed to stimulate the participant’s immune system to produce antibodies that recognize and clear amyloid beta, while the oral drug is intended to inhibit an enzyme involved in producing amyloid beta. Participants may receive the assigned study intervention for five to eight years while investigators monitor cognitive function and biomarkers.
“If the vaccine or the oral medication delays the development of Alzheimer’s in people at higher genetic risk, it would strongly support the approach of targeting amyloid beta early in the disease process,” Schneider explains. “Even a modest delay in onset—say five years—would substantially reduce the number of people who develop symptomatic Alzheimer’s and would add years of healthy life for many individuals.”
Investigators note that if the therapies show benefit in people with two copies of APOE4, those results would likely inform prevention strategies for other at-risk groups as well. The study will collect detailed clinical assessments and biological data to evaluate both safety and effects on cognition and biomarkers over time.
“Our clinicians and scientists have worked in Alzheimer’s clinical research for decades,” says Rohit Varma, MD, MPH, dean of the Keck School. “This trial reflects our continued commitment to confronting one of the greatest public health challenges of our era.”
Source: Cynthia Smith, Keck Medicine USC.
Image credit: Juan Gaertner.
Keck Medicine USC. “Study Investigates Vaccine and Oral Medication to Stop Alzheimer’s Years Before It Begins.” NeuroscienceNews, September 2017.