Abstract Details

Title Preliminary Evidence that Neflamapimod has a Beneficial Effect on Basal Forebrain Atrophy Assessed by MRI in Dementia with Lewy Bodies

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) P11 - Poster Session 11 (11:45 AM-12:45 PM)

Poster/Presentation
Number 13-009

Objective To evaluate MRI’s potential to assess treatment effects, and assess the impact of neflamapimod treatment, on basal forebrain atrophy.

Background Neflamapimod, an oral p38α kinase inhibitor, targets molecular mechanisms underlying cholinergic degeneration and in preclinical studies basal forebrain cholinergic loss. In phase 2a and 2b ("RewinD-LB") trials, neflamapimod significantly slowed clinical progression in dementia with Lewy bodies (DLB), a disorder characterized by loss of basal forebrain cholinergic neurons. Basal forebrain atrophy by MRI is correlated to cognitive decline in DLB in natural history studies, but here are no reports of the use of MRI to monitor treatment.

Design/Methods A total of 159 participants were enrolled using consensus clinical criteria in a 16-week randomized, placebo-controlled period, followed by a 32-week neflamapimod-only extension. Structural and functional MRI were performed at baseline, week 16, and week 48 in the 25 participants from the UK and the Netherlands. Volumes of the left and right basal forebrain (BF) and nucleus basalis of Meynert (NbM)—the major cholinergic cluster within the BF—were quantified.

Results Baseline volumes (mm³) were comparable between groups in the left BF [placebo=315(SD=47), neflamapimod=296(51)], right BF [309(47), 310(47)], left NbM [185(33), 168(21)], and right NbM [269(45), 253(33)]. At week 16, mean change from baseline in right BF volume increased by +8.6 (SEM 6.0) with neflamapimod and decreased by –13.3 (6.0) with placebo (difference = –22 mm³; 95% CI –39.8 to –4.1; p = 0.019). No significant group differences were observed for other volumetric measures. At week 48, change from baseline in right NbM volume was +1.9 mm³ (95% CI –5.5 to +9.3), associated with improved right BF–default mode network static functional connectivity (p = 0.019 for increase from baseline).

Conclusions These findings provide preliminary evidence that neflamapimod may reduce basal forebrain atrophy in DLB and support MRI as a tool to assess treatment effects on cholinergic degeneration.

Authors/Disclosures
John Alam PRESENTER	John Alam has received personal compensation for serving as an employee of CervoMed. John Alam has or had stock in CervoMed.
Ismail Koubiyr, PhD	Dr. Koubiyr has nothing to disclose.
Menno M. Schoonheim, PhD (Amsterdam University Medical Center)	The institution of Dr. Schoonheim has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Novartis. The institution of Dr. Schoonheim has received research support from Dutch MS Research Foundation. The institution of Dr. Schoonheim has received research support from Eurostars-EUREKA. The institution of Dr. Schoonheim has received research support from Amsterdam Neuroscience. Dr. Schoonheim has received research support from ZonMW. The institution of Dr. Schoonheim has received research support from Atara Biotherapeutics. The institution of Dr. Schoonheim has received research support from Biogen. The institution of Dr. Schoonheim has received research support from BMS. The institution of Dr. Schoonheim has received research support from Merck. The institution of Dr. Schoonheim has received research support from Cervomed/EIP. The institution of Dr. Schoonheim has received research support from ECTRIMS.

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