Irina Pikuleva, PhD: Using Efavirenz in Alzheimer Disease

“The major goal of the trial is to see the so-called target engagement—the activation of CYP46A1.”

In recent years, it was discovered that extremely low-doses of the anti-HIV therapy efavirenz—100 times lower than the standard 600 mg given to patients with HIV—can enhance the activity of the brain enzyme cytochrome P450 46A1 (CYP46A1), which converts cholesterol to 24-hydroxycholesterol and controls the major cholesterol elimination pathway in the brain.

According to Irina Pikuleva, PhD, this enhancement has also shown the ability to occasionally reduce amyloid pathology in the brain as well. To assess the possibility of utilizing this drug in patients with Alzheimer disease, Pikuleva and her colleagues are conducting a clinical trial to determine the proper dosing.

They’ll be exploring 2 possible doses: 50-mg daily and 200-mg daily in 36 patients for 20 weeks. The group will asses cognitive measurements as well, but the goal is to see target activation by measuring plasma levels of 24-hydroxycholesterol.

The Carl F. Asseff Professor of Ophthalmology and the Director of the Visual Sciences Research Center at Case Western Reserve University, spoke with NeurologyLive at the ADDF’s 19th Annual Conference in Jersey City, New Jersey, to further discuss the trial.