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New Study Suggests Experimental Drug May Delay Alzheimer’s Onset

Recent research indicates that an experimental medication may significantly decrease the likelihood of Alzheimer’s-related dementia in individuals genetically predisposed to develop the disease in their 30s, 40s, or 50s. Conducted by the Knight Family Dominantly Inherited Alzheimer Network-Trials Unit (DIAN-TU) at Washington University School of Medicine in St. Louis, this study offers compelling insights into the potential for early intervention in Alzheimer’s disease.

The findings, published on March 19 in The Lancet Neurology, represent groundbreaking evidence suggesting that addressing amyloid plaque accumulation in the brain years prior to the appearance of symptoms can lead to a postponement of Alzheimer’s dementia.

Study Design and Population

The international study included 73 participants with unique, hereditary genetic mutations known to result in excessive amyloid production in the brain, which almost guarantees the eventual development of Alzheimer’s disease in middle age. Among a subgroup of 22 participants who had no cognitive impairments at the study’s onset and received the drug treatment over an average of eight years, the study found a reduction in the risk of developing symptoms from nearly 100% to approximately 50%. This finding was corroborated by extensive data analysis.

Insights from the Research Team

Senior author Randall J. Bateman, MD, highlighted the study’s significance, noting that all participants were at high risk yet some remained symptom-free. “We do not yet fully understand how long they will stay cognitively healthy,” he explained, adding that ongoing treatment with another anti-amyloid agent aims to further extend this symptom-free period. “The outcome suggests we may be able to postpone the emergence of Alzheimer’s symptoms, thereby enhancing the quality of life for these individuals.”

Amyloid Hypothesis: Supporting Evidence

The results lend credence to the amyloid hypothesis, which posits that amyloid plaque accumulation is a precursor to dementia. The research team assessed whether the experimental anti-amyloid drug could stave off dementia onset by eliminating these plaques. This study follows the Knight Family DIAN-TU-001, the first-ever Alzheimer’s prevention trial launched in 2012, which examined anti-amyloid drugs’ capabilities as preventative measures for the disease.

Participants in the trial displayed no to minimal cognitive decline and were selected based on their family history of Alzheimer’s, entering the study 15 years prior to or 10 years following their anticipated age of onset.

Previous Findings and Drug Efficacy

Upon concluding the initial trial in 2020, the research team found that gantenerumab, produced by Roche and Genentech, effectively lowered amyloid levels and improved certain Alzheimer’s biomarkers. However, cognitive benefits were not immediately apparent since participants without symptoms did not exhibit decline, prompting the continuation of the study to explore the effects of extended treatment.

All participants eligible for the extension study received the anti-amyloid medication gantenerumab, eliminating an internal control group. The researchers instead compared outcomes of extension participants with those from the DIAN Observational study, which contained untreated individuals.

Trial Adjustments and Subsequent Findings

Originally set for three years, the extension study was curtailed in mid-2023 following Roche/Genentech’s decision to halt gantenerumab’s development due to lack of efficacy in earlier symptomatic Alzheimer’s patients in their Phase 3 trials. At the time of termination, the average participant had received treatment for roughly 2.6 years.

Analysis suggests that the timely removal of amyloid plaques can delay symptom emergence and progression of dementia, notably for participants who began treatment while symptom-free and received the drug for an extended duration. While those treated for shorter periods exhibited no cognitive improvements, the results contend that earlier and prolonged treatment may be essential for prevention.

Safety and Side Effects

Although gantenerumab and other anti-amyloid drugs have shown promise, some participants experienced amyloid-related imaging abnormalities (ARIA), detectable through brain scans. Most cases were asymptomatic and resolved naturally, although a minority required treatment cessation due to severe ARIA. Importantly, there were no reported deaths or severe adverse events associated with the treatment.

Future Directions: Research and Implications

The Knight Family DIAN-TU has initiated the Knight Family DIAN-TU Amyloid Removal Trial to further investigate how long the onset of dementia can be delayed through amyloid removal. Many participants from the previous extension have transitioned to lecanemab, recently approved by the FDA, intended for those with symptomatic Alzheimer’s. Preliminary data from this phase is pending analysis, and a grant proposal is currently under review for extended funding.

Though the current trial focused on genetic forms of Alzheimer’s, the implications of these findings are anticipated to broadly influence prevention strategies for all Alzheimer’s variants. Both early-onset and late-onset forms are characterized by amyloid accumulation decades before cognitive symptoms manifest, reinforcing the relevance of this study.

Potential for Population-Wide Preventive Strategies

As optimism grows regarding the translation of these results into broader Alzheimer’s prevention efforts, researchers express hope that similar outcomes may soon emerge from late-onset trials. “The potential to delay the onset of Alzheimer’s disease for many people is within reach,” Bateman noted. “With ongoing advancements, we might soon witness effective preventive measures available for at-risk populations.”

While gantenerumab has been discontinued, other anti-amyloid drugs are under examination as potential preventative options for Alzheimer’s disease. Maria C. Carrillo, PhD, the Alzheimer’s Association’s chief science officer, emphasized the importance of further investigations into these findings. “These results reveal a significant opportunity to lower beta amyloid levels as a preventive approach to Alzheimer’s disease,” she stated. “Ending this research can pave the way for the development of groundbreaking therapies that can ultimately benefit millions.”

The Knight Family DIAN-TU is now assessing remternetug, an investigational amyloid-removing drug, in a new trial targeting younger participants at risk for Alzheimer’s, aiming to determine if early intervention can effectively prevent symptom development.

Funding for the DIAN-TU-001 segment has come from various sources, including the National Institutes of Health, the Alzheimer’s Association, and private sector contributions, underscoring the collaborative effort essential to advancing Alzheimer’s research.

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