Why new Alzheimer's drugs don't work | Mike Greicius, Stanford University School of Medicine
Sep 12, 2024
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Mike Greicius, a Stanford neurologist and expert on Alzheimer's treatments, discusses the recent surge of amyloid-clearing drugs. He critiques their effectiveness, suggesting they may cause more harm than good. Greicius highlights the skepticism among doctors regarding these drugs due to minimal cognitive benefits seen in trials. He also explores genetic factors influencing Alzheimer's risk and the shift in research focus from amyloid to tau proteins, offering a glimpse of hope for more effective therapies in the future.
Mike Greicius criticizes the new Alzheimer’s drugs for their minimal clinical benefits and potential harmful side effects for patients.
There is growing optimism for future Alzheimer’s therapies targeting tau proteins and genetic factors, shifting focus away from amyloid plaques.
Deep dives
Concerns About New Alzheimer's Treatments
Recent developments in Alzheimer's treatment include the introduction of three new drugs aimed at eliminating amyloid plaques in the brain, which have been linked to the disease. However, concerns have been raised about their effectiveness, particularly by neurologist Mike Gratius, who asserts that the clinical improvements observed in trials are minimal and may not reflect real benefits for patients. For instance, the reported changes on clinical outcome measures were between a quarter and two-thirds of a point, far less than the one to two-point change necessary for clinicians to note a significant difference in patient condition. Gratius believes that the drugs may be ineffective, and even harmful, given the serious side effects linked to their use.
The Role of Amyloid and New Therapeutic Approaches
While amyloid plaques have been the focus of recent treatments, Gratius argues that they may not be the appropriate target for therapeutic intervention. Research has shown that the presence of amyloid plaques does not necessarily correlate with symptoms of cognitive decline, indicating that other factors, such as tau protein, may need more attention. New clinical trials are exploring therapies targeting tau and genetic factors associated with Alzheimer's, promising a shift in focus for future treatments. Gratius expresses optimism about these upcoming therapies and their potential for delivering meaningful clinical improvements and insights into the disease.
The Genetic Component and Future Research Directions
Genetics play a significant role in Alzheimer's risk, with the ApoE4 variant being a major contributor. Understanding how this and other genetic factors influence disease progression could open avenues for effective intervention strategies. Research is particularly focused on identifying protective factors in individuals with ApoE4 who remain healthy into old age, potentially uncovering new targets for treatment. As the field continues to evolve with research into alternative targets like inflammation and tau, there is growing hope that more effective therapies will emerge in the near future.
In the past few years, Big Pharma has released not one, but three new treatments for Alzheimer’s disease.
Aducanemab (2021), Lecanemab (2023), and Donanemab (2024), are the first treatments to effectively clear the brain of amyloid plaques — the sticky protein clumps whose build-up in the brain has defined the disease for decades. The problem? They may not help patients at all.
Today’s guest, Stanford neurologist Mike Greicius, considers the new amyloid-clearing drugs a major disappointment — and worse, says they likely do more harm than good for patients.
Despite this critique, Greicius, thinks that the next few years will be an exciting time for novel Alzheimer’s therapies, as growing biological understanding of Alzheimer’s risk and resilience bear fruit with promising new approaches to treatment.
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