Frontotemporal dementia (FTD)

Frontotemporal dementia (FTD) is a rare neurodegenerative disease, but it is one of the most common causes of early onset dementia, characterized by progressive deterioration in behavior, personality, and language abilities. It affects an estimated 50,000 to 60,000 people in the United States and roughly 110,000 in the European Union, with potentially higher prevalence in Asia and Latin America, and it is the most common form of dementia for people under 60. Despite this prevalence and unmet need, there are no FDA- or EMA-approved treatment options available for any form of FTD.

Pathologically, FTD is characterized by significant neuronal loss in the frontal and temporal regions of the cortex. The pathogenic drivers underlying the neuronal loss are, in most cases, intraneuronal inclusions in those two regions of the brain containing either the protein tau or TDP-43 (transactive response DNA binding protein); intranuclear inclusions of fused in sarcoma (FUS) are also seen, but in fewer than 10% of patients. Patients with FTD frequently develop symptoms such as behavioral changes, lapses in judgment, and diminished language skills when they are in their 40s and 50s with the disease running its course in 7-10 years.

There are several subtypes of FTD, including nonfluent/agrammatic variant primary progressive aphasia (nfvPPA) which primarily affects speech and grammar. People with nfvPPA often struggle to speak fluently, form complete sentences, or pronounce words clearly. Unlike Alzheimer’s disease (AD), memory may remain intact in the early stages — but speaking becomes noticeably effortful and labored.

At the heart of these hallmark symptoms of nfvPPA is the loss of brain cells (neurons) in regions of the brain that are responsible for speech, a major cause of which is the buildup of abnormal tau protein. Recent studies in animal models have shown that accumulation of abnormal tau leads to defective transport of products along the body of the neuron (axons), which is important for its proper growth and survival.

Neflamapimod’s Potential in FTD

The rationale for potentially evaluating neflamapimod as a treatment for FTD is based on the effects of p38 alpha on axonal transport and tau pathologies, as well as atrophy of the basal forebrain cholinergic system being a driver of disease and the mechanisms that neflamapimod targets being operative in FTD.

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 result in accumulation of abnormal tau protein and neuron dysfunction.

In November 2024, CervoMed’s investigational drug, neflamapimod, received Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) for the treatment of  FTD. This designation is granted to drugs intended to treat rare diseases or conditions affecting fewer than 200,000 people in the US. The designation provides incentives such as tax credits for clinical trials and potential market exclusivity. CervoMed plans to initiate a Phase 2a trial for neflamapimod in a specific FTD subtype, nonfluent/agrammatic variant of primary progressive aphasia (nfvPPA), in mid-2025.

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.

PRESENTATIONS AND PUBLICATIONS