University of Missouri and Altos Labs register sirolimus trial in 225 healthy women with APOE4

University of Missouri and Altos Labs register sirolimus trial in 225 healthy women with APOE4

On July 27, a phase I study was added to the ClinicalTrials.gov registry. Women aged 45 to 65 will be randomly assigned to receive sirolimus or placebo. The participants, investigators, and outcome assessors will not know who received the drug. Recruitment is scheduled to begin in December 2026.

APOE4 is a variant of the APOE gene associated with an increased risk of late-onset Alzheimer's disease. Researchers study carriers for changes in the brain that occur before memory problems develop. One such measure is cerebral blood flow, which is the amount of blood passing through brain tissue each minute.

Sirolimus, also known as rapamycin, reduces the activity of mTOR, a cellular regulator that receives signals about nutrient availability, growth factors, and energy stores. The new protocol will test whether a four-week course changes blood flow in the brain.

Ai-Ling Lin's group previously conducted an open-label pilot study. 23 adults without cognitive impairment took 1 mg of sirolimus daily for four weeks, and nine of them carried APOE4. In a preprint, the authors reported increases in blood flow of more than 15% in several brain regions within this subgroup. The new study will compare sirolimus with placebo in parallel groups, instead of comparing only the same participants before and after treatment.

The primary measure will be the change in blood flow assessed by MRI. The researchers will also assess cerebrovascular function, inflammatory markers, and glucose metabolism, then compare the results between the two groups.