Again and again … and again, drugs have failed in clinical trials for Alzheimer’s disease. According to a new report, in the last decade, 146 drugs have failed in clinical trials for Alzheimer’s.
Again and again … and again, drugs have failed in clinical trials for Alzheimer’s disease. According to a new report, in the last decade, 146 drugs have failed in clinical trials for Alzheimer’s.
The prevailing theory of Alzheimer’s is that a protein called beta-amyloid accumulates in the brain, causing the damage that leads to cognition and memory problems. Later in the disease, another protein accumulates, called tau. Most drugs being developed or have been tested, have focused on preventing or clearing beta-amyloid. But even when the drugs are effective in clearing amyloid, they seem to have little impact on the cognition and memory issues.
As a result, drug companies are testing these compounds in patients earlier and earlier in the disease stage, suggesting a trend toward prevention rather than treatment.
A recent report by the U.S. Centers for Disease Control and Prevention (CDC) published in the journal Alzheimer’s & Dementia, projected that incidence of the disease will double in the next 40 years unless a cure or preventive measures are found. Much of this is related to the aging population and overall population growth. But part of the CDC’s report was a call for early diagnosis and support of caregivers. Robert Redfield, director of the CDC, stated, “Early diagnosis is key to helping people and their families cope with loss of memory, navigate the health care system, and plan for their care in the future.”
And, in fact, one of Biogen’s most-anticipated drugs, aducanumab, for Alzheimer’s, is being tested in such early-stage AD patients that it is likely to be viewed as more of a preventative than a treatment, if effective.
Recently, the National Institute on Aging, the Alzheimer’s Association, several foundations, Banner Alzheimer’s Institute, and Novartis and Amgen launched two clinical trials focused on prevention instead of treatment. Eliezer Masliah, neuroscience chief of NIA, told the Associated Press, “What we have been learning, painfully, is that if we really want to come up with therapies that will modify the disease, we need to start very, very, very early.”
To participate in the studies, interested people must join GeneMatch, a registry of people between the ages of 55 and 75 who have not been diagnosed with mental decline. They are then given a cheek-swab kit to test for the APOE4 gene. People who have evidence of the APOE4 gene doesn’t mean they will develop Alzheimer’s disease, but they are at higher risk. Since GeneMatch launched three years ago, more than 70,000 people have enrolled.
Being in GeneMatch doesn’t mean you will be told about your test results or if you will be selected for either of the clinical trials. But if selected for either of the prevention trials, they must agree to learn their APOE4 status, have at least one copy of the gene, and undergo periodic brain scans and memory and cognition tests every six months. They will receive either experimental drugs or placebo for several years. The trials are in patients age 60 to 75.
One of the clinical trials will evaluate individuals with two copies of EPOE4. They will receive injections every couple months of a drug to help the immune system clear amyloid plaque from the brain or daily pills of a drug that prevents the first steps of plaque formation, or a placebo.
The other trial is in patients with two copies of APOE4 or one copy plus evidence on brain scans of plaque beginning to accumulate. The patients will receive one of two doses of the drug to prevent plaque formation or placebo.
The early prevention focuses on what is dubbed the “silent stage,” of the disease. In an August story, Pierre N. Tariot, co-director of the Alzheimer’s Prevention Initiative and director of Banner Alzheimer’s Institute, stated, “If we can interfere with the production of abnormal forms of amyloid using disease-modifying treatments and stop them from forming harmful plaques in the brain, we may be able to delay the onset, slow the progression, or even stop Alzheimer’s from developing.”
At least one of the drugs being tested is CNP520, a BACE1 inhibitor. BACE1 is an enzyme involved in the production of beta-amyloid.
More information about the clinical trials can be found at the Generation Program Alzheimer’s Prevention Initiative website.
