Neflamapimod improves inflammation-driven cognitive deficit

Newsletter # 90



Animal models


Neflamapimod is an orally available and brain-penetrant inhibitor of alpha isoform of p38 MAPK which is a key enzyme involved in the production of inflammatory mediators under various inflammatory disease conditions.
Neflamapimod, previously granted a fast-track designation in Lewis bodies dementia (LBD) by the FDA, was announced to improve the cognitive composite score in LBD trial. In an early Alzheimer's disease study it was suggested that cognition was improved in the patients with the highest tertile of trough plasma drug concentration of Neflamapimod.


Preclinical data showed that 3 weeks treatment of aged rats with Neflamapimod improved their performance in the Morris water maze paradigm along with a reduced hippocampal IL-1β level.
The data of Neurofit indicates that 1 week treatment with Neflamapimod is sufficient to improve lipopolysaccharide (LPS)-induced cognitive deficit in the mice. LPS is known to induce brain inflammation. Neurofit's finding thus strengthens the potential role of p38 MAPK in inflammatory-based cognitive disorders.



  • ■ The graph shows a marked reduction in the level of spontaneous alternation of LPS-mice (red column) during the T-maze task as compared to that of control mice (blue column). The decrease in the alternation reflects stereotypic and repetitive behavior, a common symptom in dementia patients (1).

    ■ The treatment of LPS-mice with Neflamapimod (purple column) significantly increases the alternation performance of LPS-mice.
    Neflamapimod was administrated at 0.5 mg/kg twice daily for 7 days.

    (     1 ) : DOI: 10.1177/1533317513481094


    **, p ≤ 0.01; ***, p ≤ 0.001 significantly different as compared to LPS/Vehicle group (n=10 mice per group).


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  • Other anti-inflammatory drugs were also shown effective in the model of LPS-induced cognitive deficit in mice (see the following link: Neurofit posters)


NEUROFIT offers a range of validated in vitro and in vivo screening tests for psychiatry and neurology.

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