Microglial Modulator May Improve Cognitive Function in Patients With MCI

BOSTON—A novel microglial modulator was well tolerated and associated with sustained cognitive benefit in executive function and verbal memory for at least 64 weeks in patients with mild cognitive impairment (MCI), according to research presented at the 2013 Alzheimer’s Association International Conference.

“This is one of the first studies indicating that this neuroinflammatory inhibitor [CHF5074] may be able to improve cognition in people with MCI who carry the APOE4 gene,” said Joel S. Ross, MD, Founder and Chief Executive Officer of the Memory Enhancement Center of America, in Eatontown, New Jersey. “CHF5074 was well tolerated by people with MCI at doses up to and including 400 mg/day.”

Dr. Ross and colleagues reported results of a 76-week open-label extension study involving CHF5074 (Chiesi Pharmaceuticals; Parma, Italy). The extension study followed a 14-week, double-blind, placebo-controlled study of 96 patients with MCI that assessed three titrated dose regimens (200, 400, and 600 mg/day). A total of 74 patients enrolled in the extension study and received CHF5074 at the dose equal to that of their originally assigned double-blind study cohort. All participants were monitored for vital signs, cardiac activity, neuropsychologic performance, and safety laboratory parameters.

In the open-label study, 26 patients received 200 mg/day of CHF5074, 21 patients received 400 mg/day, and 27 received 600 mg/day. At week 40, 14 patients dropped out—four in the 200-mg/day group, two in the 400-mg/day group, and eight in the 600-mg/day group. Three dropouts were due to adverse events. Gastrointestinal disorders were the most frequent treatment-emergent adverse events; diarrhea was reported by 1.4% of patients taking 200 mg/day of CHF5074, by 6.3% of patients taking 400 mg/day, and by 16.0% of patients taking 600 mg/day.

“An interim analysis of cognitive tests of 27 patients reaching study week 88 showed statistically significant, dose-dependent improvements in participants’ cognitive abilities,” said Dr. Ross. “APOE4 carriers performed significantly better than APOE4 noncarriers on Immediate Word Recall and Trail Making Test–A, with improvements representing 25% to 38% of baseline scores.

“Inhibiting microglia has significant treatment potential,” Dr. Ross concluded.

—Colby Stong
Editor