How neflamapimod works
Alzheimer’s disease is a neurodegenerative disorder in which the slow death of nerve cells in the brain results in a progressive decline in memory and the ability to process and store information. These symptoms are thought to be caused by the clumping and build-up of beta-amyloid and tau proteins, possibly blocking cell-to-cell communication and activating immune system cells, which in turn trigger inflammation.
Neflamapimod works by inhibiting an enzyme called p38 mitogen-activated protein kinase alpha (p38α). In a normal situation, that p38α enzyme is involved in regulating inflammation. However, in a disease context, p38α malfunctions and is thought to be involved in beta-amyloid or tau-induced toxicity and excessive inflammation.
Neflamapimod in clinical trials
The pharmacological effects of neflamapimod were first evaluated in a pre-clinical study in mouse brains. Results of that study, published in the Journal of Alzheimer’s Disease, showed that neflamapimod improved cognitive performance and inflammation, and appeared to decrease beta-amyloid accumulation, in the brains of the animals.
Researchers conducted another study to evaluate the effects of neflamapimod in human cells grown in the laboratory. That study showed that neflamapimod could have a new mechanism of action through the reversal of endosomal dysfunction — a non-working compartment inside cells — seen in Alzheimer disease.
These results provided the rationale to test the treatment in humans.
The safety and tolerability of neflamapimod were assessed in two Phase 2 clinical trials — NCT02423122 and NCT02423200 — treating people with mild Alzheimer’s disease. The results, announced by EIP Pharma, showed that neflamapimod led to improvements in memory and learning, as well as a reduction in beta-amyloid plaques in the brain. The therapy was well-tolerated in both studies, and no safety issues were identified.
Neflamapimod is currently being assessed in two additional Phase 2 clinical trials.
The first study (NCT03402659), called REVERSE-SD, is a proof-of-concept trial to demonstrate whether neflamapimod can significantly improve memory compared with placebo. The study is active but no longer recruiting participants. Preliminary results from 16 individuals were released and published in the journal Annals of Clinical and Translational Neurology. The researchers found that neflamapimod may improve memory and reduce amyloid-beta production.
The second trial (NCT03435861) is designed to assess the efficacy of neflamapimod in early Alzheimer’s disease patients. The primary objective is to compare the level of inflammation following 12 weeks of treatment with neflamapimod or placebo. The trial is currently recruiting an estimated 40 participants at University Hospital Toulouse in France. Find more information here.
Earlier this year, EIP Pharma announced it had raised $11.2 million to continue the development of neflamapimod.
The most common adverse events associated with neflamapimod use are sleepiness or drowsiness, and mild diarrhea.
Last updated: September 9, 2019
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