A phase 2 proof-of-concept clinical study, AscenD-LB (NCT04001517) has begun for neflamapimod (EIP Pharma,Cambridge, MA) as a treatment for the cognitive dysfunction associated with dementia with Lewy bodies (DLB). Accounting for approximately 20% of all-cause dementia, DLB is a synucleinopathy characterized by progressive dementia and fluctuating cognition, sleep disturbances, visual hallucinations, and parkinsonism.
Activation of p38 alpha kinase has been linked to neurotoxicity of alpha-synuclein aggregates found in Lewy bodies. This study is designed to study whether p38 alpha kinase with the brain penetrant small molecule neflamapimod can reverse synaptic dysfunction in the hippocampus, which is associated with DLB.
The 16-week treatment study will assess 80 patients randomly assigned to receive neflamapimod or placebo, using a neuropsychologic test battery to evaluate attention, executive function, and visuospatial deficits.
“We believe that by targeting synaptic dysfunction, neflamapimod may improve the cognitive impairment associated with DLB with the potential to change the course of a patient's disease,” said John Alam, MD, founder and CEO of EIP Pharma. “This trial, along with our 2 other ongoing trials in Huntington's and Alzheimer's disease, will provide us with a stronger understanding of the potential of neflamapimod to reverse synaptic dysfunction in a broad range of neurodegenerative diseases."
Shruti Bhandari, MD; Rohit Kumar, MD; Megan Nelson, MD; Donald Miller, MD; and Brian J. Williams, MD
Ilka Kleffner, MD; Catharina C. Gross, PhD; Marius Ringelstein, MD; Jörg Rehrmann, MD; Markus Kraemer, MD; and Jan Dörr, MD
Jennifer E. Fugate, DO