Dementia with Lewy Bodies

Dementia with Lewy bodies (DLB) is a progressive disease where a protein known as alpha-synuclein builds up to form structures called Lewy bodies in the parts of the brain that control cognition, behavior and movement. Patients with DLB incur higher healthcare costs, have longer hospitalizations, report lower quality of life, and have caregivers with higher levels of distress when compared with patients with Alzheimer’s Disease (AD). No treatments have been approved by the US FDA or European Medicines Agency for DLB. CervoMed is developing a drug, neflamapimod, to reverse and potentially slow the synaptic dysfunction that contributes to this neurological decline. Results from an exploratory phase 2a study showed that neflamapimod improve cognitive and motor function in patients with mild to moderate DLB.  A phase 2b study in DLB to confirm the findings from phase 2a was initiated in the second quarter of 2023 and is expected to report the primary efficacy results in the second half of 2024.

The Role of Synaptic Dysfunction in Dementia with Lewy Bodies

The brain has billions of neurons that connect in the brain through synaptic connections. Evidence suggests that synaptic dysfunction results from a combination of excessive inflammation and the toxicity of alpha synuclein. In DLB, this occurs in a specific part of the brain called the basal forebrain and impacts a type of nerve called cholinergic neurons. The resulting cholinergic dysfunction is thought to cause the decline in attention, judgement, reasoning and other symptoms associated with DLB, including mobility impairment. Synaptic dysfunction in the basal forebrain is reversible in animal models, suggesting that therapeutics targeting basal forebrain cholinergic dysfunction have the potential to reverse the cognitive and motor impairments in DLB, such as neflamapimod.

p38 alpha – A Driver of Synaptic Dysfunction

p38 alpha is an enzyme that is activated in neurons in times of stress and disease. While p38 alpha plays an important role in protecting cells from acute injury, chronically activated p38 alpha activity within neurons can damage synapses and contribute to alpha-synuclein-associated toxicity. If untreated, synaptic dysfunction will progress and result in neuron loss.

CervoMed is developing an oral p38 alpha inhibitor, neflamapimod, to reverse synaptic dysfunction and improve the cognitive deficits associated with DLB. A phase 2a exploratory placebo-controlled clinical study (named “AscenD-LB”) evaluating neflamapimod in patients with mild-to-moderate DLB has been conducted and the results indicate that neflamapimod has significant positive effects, compared to placebo, on outcomes on the gold-standard dementia rating scale (Clinical Dementia Rating Sum of Boxes, CDR-SB) and on a measure of functional mobility (Timed Up and Go, TUG, test). In addition, at the higher of two doses evaluated in the study, neflamapimod showed significant improvement, compared to placebo, on a cognitive test battery that assessed attention and executive function. The results from this trial were published in the journal Nature Communications in September 2022.

A phase 2b study in DLB to confirm the findings from phase 2a was initiated in the second quarter of 2023 and is expected to report the primary efficacy results in the second half of 2024.

Scientific data for neflamapimod has been published in certain medical journals and presented to the medical and scientific community at various medical meetings.  Click below to access the data presentations.


"The data from the trial of neflamapimod in DLB are very encouraging, setting the stage for more extensive testing. There are no approved treatments for DLB, the second most common cause of neurodegenerative dementia, and there is an urgent need to find therapies for this severe and progressive disorder."

Jeffrey L. Cummings, MD, ScD, Joy Chambers-Grundy Professor of Brain Science and Director of the Chambers-Grundy Center for Transformative Science, UNLV School of Integrated Health Sciences