Crenezumaba drug developed to treat Alzheimer’s diseasedid not stop or slow cognitive decline in patients with a genetic mutation that greatly increases the risk of developing the disease, as results from a decade-long clinical trial have shown.
The mutation seen in the few hundred study participants from extended families in Colombia means they are virtually certain of developing Alzheimer’s between the ages of 40 and 50, and most likely death is around the age of 60.
The research was the first to test a drug designed to delay or halt mental decline in people who have a genetic predisposition for Alzheimer’s but have not yet experienced any symptoms.
Crenezumab: Here’s why it didn’t work
“We are disappointed that the treatment did not demonstrate a statistically significant clinical benefit“, Affirmed the Doctor Eric Reimanexecutive director of the Alzheimer’s Institute banner and one of the leaders of the study, announcing the results. “At the same time, we are proud of the impact this study has had in shaping a new era in Alzheimer’s prevention research and are extremely grateful to the research participants and their families.“.
“This study, the data, samples and findings we will share with the research community, and the related work we and others are doing promise to further accelerate the evaluation and approval of future preventive therapies.”Continued Dr. Reiman.
Crenezumab is an experimental monoclonal antibody designed to neutralize neurotoxic oligomers, a form of beta-amyloid. The drug is characterized by technology IgG4 developed to minimize the inflammatory response in the brain, which may lead to a lower risk of having certain magnetic resonance imaging (MRI) abnormalities known as ARIA (Amyloid-Related Imaging Abnormalities). Crenezumab is an investigational drug that was discovered by the Swiss biotech company AC Immune SA.
In order to carry out the research, 252 volunteers belonging to the largest extended family in the world with ADAD (Autosomal Dominant Alzheimer’s Disease) in Colombia were involved, with 94% of the participants completing the study.. Two-thirds of the participants carried the Presenilin 1 E280A mutation which typically causes cognitive impairment due to Alzheimer’s disease by age 44. Participants were randomized to receive crenezumab, or placebo, for five to eight years. During the study, the dose of crenezumab was increased as knowledge evolved about potential therapeutic approaches for Alzheimer’s disease.
“While this is a disappointing result, we would like to thank the participants and their families – they made a huge contribution to advancing both the understanding and research of new treatments for familial Alzheimer’s.“, he has declared Levi Garraway, Chief Medical Officer of Genentech and responsible for global product development: “We remain committed to providing further scientific evidence to advance the way Alzheimer’s disease is understood, diagnosed and treated. ”
In 2019, Roche stopped two more studies of crenezumab in people in the early stages of the more common type of Alzheimer’s because the drug was unlikely to provide any benefit.
“This is certainly disappointing“, He wrote to Alzforum Dave Morgan of the Michigan State University in Grand Rapids. He noted that crenezumab has unique characteristics, including a low rate of side effects and a purported ability to inhibit Aβ aggregation, which initially suggested it might work well (full comment below). However, other researchers have noted crenezumab’s limitations. “This is not unexpected, because the Phase 2 studies were not positive “, he has declared Lon Schneider of the University of Southern California, Los Angeles.
These latest findings add to a series of drug failures that target amyloid, a protein that plays an important role in Alzheimer’s by forming plaques in the brain.. In a controversial move, in 2021, the U.S. Food and Drug Administration granted its first approval for an anti-amyloid drug. Aduhelmdespite acknowledging that it was unclear whether the drug could actually help patients.
Many Alzheimer’s disease experts criticized the FDA’s decision at the time, pointing to the disappointing history of anti-amyloid treatments .
Autosomal dominant Alzheimer’s disease (ADAD; also known as familial AD or dominantly inherited AD [DIAD]) is a rare inherited form of Alzheimer’s disease caused by single gene mutations in the APP, PSEN1 or PSEN2 genes. Less than 1% of all Alzheimer’s cases worldwide are believed to be caused by genetic mutations.
It usually has a much earlier onset than the more common sporadic Alzheimer’s disease, with symptoms developing in people between the ages of 30 and 60. If an individual has one of these mutations, they are almost certain to develop Alzheimer’s and there is a 50% chance that they will pass it on to their offspring.
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