UCSF Begins Patient Screening for New Alzheimer’s Treatment Trial

A groundbreaking clinical trial is set to launch this week, aiming to revolutionize Alzheimer’s disease treatment by targeting both amyloid and tau proteins simultaneously. Spearheaded by researchers at UC San Francisco, this national study represents the first large-scale effort to evaluate combination therapies in the fight against the most common neurodegenerative disorder.

Amyloid plaques and tau tangles, two hallmark proteins intertwined with the pathology of Alzheimer’s, have long been the focus of therapeutic research. While existing FDA-approved drugs have primarily targeted amyloid accumulation, tau remains a critical yet elusive target. Notably, amyloid plaques can be present in the brain for over a decade without causing symptoms, which typically emerge only after tau begins to accumulate and disrupt neural function. The new trial will explore whether addressing both amyloid and tau from the earliest biological signs of tau build-up can slow or halt cognitive decline more effectively than single-agent therapies.

This innovative study aims to enroll up to 825 participants across multiple U.S. sites, including individuals with early cognitive impairment as well as asymptomatic people showing biological markers of Alzheimer’s. All participants will receive active treatment at some stage during the trial, which will be adaptive in nature: additional drugs, sometimes from competing pharmaceutical companies, will be incorporated over time to optimize therapeutic impact.

During the initial six months, participants will receive either a placebo or donanemab, an amyloid-targeting antibody already approved for slowing Alzheimer’s progression. Subsequently, subjects will be administered a tau-directed therapy, either alone or in combination with donanemab, for two years. The first tau drug to be tested is AADvac1, which harnesses the immune system to recognize and neutralize pathological tau proteins, potentially preventing the neurotoxic cascade that underpins cognitive deficits.

Co-led by Keith Johnson, MD, of Massachusetts General Hospital and Harvard Medical School alongside UCSF’s Adam Boxer, MD, PhD, the Alzheimer’s Tau Platform (ATP) trial is strategically designed not only to expedite tau-targeted drug development but also to reduce burden and cost for patients participating in cutting-edge Alzheimer’s research. The trial incorporates rigorous biomarker screening involving amyloid and tau imaging, alongside continuous cognitive assessments.

Funded by the National Institutes of Health (NIH), this landmark study promises to generate a rich repository of clinical data and biological samples. Such resources are expected to deepen scientific understanding of Alzheimer’s progression and assist in refining future interventions. By integrating novel therapeutic approaches and an adaptive trial design, researchers hope to illuminate a path toward more effective treatment options for millions affected by this devastating disease.