Older people — ages 60 to 75 — in good cognitive health but with two copies of the “risk gene” for Alzheimer’s disease (AD) are being asked to take part in Generation Study, a collaborative and global research project investigating treatments that might stop the disease from developing.
Two copies of the APOE4 gene are inherited, one from each parent, and people who meet age and health requirements but do not know of their genetic risk status can ask that it be determined by joining the Gene Match Program, run by led by the Banner Alzheimer’s Institute. Some may then be invited to take part in the study.
Generation Study will test the potential of two investigative therapies against placebo in preventing amyloid beta build-up in the brain, which is thought to be associated with Alzheimer’s development. Some 90 worldwide institutions — in the U.S., Canada, Australia and across Europe — are involved (those in the U.S. can be found here).
Banner Alzheimer’s Institute, based in Arizona, is running the trial with Novartis, which is providing the drugs to be tested, CAD106 (a vaccine therapy) and CNP520 (an oral treatment), and Amgen, which helped develop CNP520. Both are designed to reduce amyloid beta accumulation in the brain and have been examined in other clinical trials.
The study runs through May 2024. A Phase 2/3 trial (NCT02565511), it expects to recruit well over 1,000 people. A separate but related study, Generation S2 (NCT03131453), is testing CNP520 against placebo in about 2,000 people across the U.S.
To qualify, a person must meet the age requirements, have no evidence of dementia or Alzheimer’s — i.e., must have memory and thinking abilities normal for his or her age — and two copies of the specific type of APOE4 gene that is associated with AD (there are three versions of this gene, but only one is thought to be tied to the disease).
“One of the challenges in developing new medications for Alzheimer’s is that researchers tend to test medications on people with more advanced Alzheimer’s, and the medications are simply not proving to be effective,” Lon Schneider, the study’s lead investigator at the Keck School of Medicine at the University of Southern California (USC), said in a press release. “By intervening 10 to 12 years before Alzheimer’s manifests, we may be able to stop it before it begins or delay the symptoms.”
Generation Study is divided into three parts:
- A simple questionnaire is given first to determine eligiblity
- Those eligible but without knowledge or proof of risk genes can register with GeneMatch. Genetic testing is done via a painless cheek swab, whose kit is sent to the person by mail or under a doctor’s supervision. Participants will not be told of APOE results and results will be kept confidential.
- Generation Study participants will receive investigational medication, or placebo, and care from their study doctor or research staff. Treatment will be given for at least 60 months, and possibly up to 96 months. Regular appointments with a study physician or research staff are required.
Participants will be randomized to receive either medication or placebo. Both active medications target amyloid beta in two ways: the vaccine helps the body develop antibodies against amyloid beta; the oral medication blocks an enzyme that creates amyloid beta.
Participants may opt out of the study at any time, and will be informed of all risks and benefits before each step is initiated.
Those aware of having two copies of the APOE4 gene and interested in taking part in Generation Study are asked to contact the Alzheimer’s Prevention Registry at info@endALZnow.org or by calling 1‐888‐STOP‐ALZ (1-888-786-7259). Those who don’t know their genetic background are asked to join the GeneMatch program.
About half of all Alzheimer’s patients carry the APOE4 gene, but only about 2 to 3 percent carry two copies.
“If we can delay the onset of Alzheimer’s by five years, for example, the incidence of the illness would drop by half,” Schneider said. “It would also give individuals five more years without symptoms of the illness.”
Generation Study is supported by the National Institute on Aging (NIA), the Alzheimer’s Association, Forest Biometrics Research Institute (FBRI), GHR Foundation and the Banner Alzheimer’s Foundation. Its sponsors include Banner Health, Novartis and Amgen.