Early Data Show Neflamapimod’s Potential to Prevent Nerve Cell Degeneration

Early Data Show Neflamapimod’s Potential to Prevent Nerve Cell Degeneration

Treatment with EIP Pharma’s investigational therapy neflamapimod (VX-745) can restore nerve cells’ communications and prevent their progressive degeneration and death, new preclinical results show.

All together these data further support neflamapimod’s use to treat several neurodegenerative disorders characterized by impairment in nerve cell communications, such as Huntington’s disease.

These data were presented in two scientific posters, “Role of p38α MAP kinase in amyloid-β derived diffusible ligand (ADDL) induced dendritic spine loss in hippocampal neurons,” and “Effects of p38α MAP kinase inhibition on the neurodegenerative phenotype of the Ts2 Down Syndrome mouse model,” during the the 2019 Alzheimer’s Association International Conference (AAIC) in Los Angeles.

Neflamapimod is an oral small molecule designed to be able to penetrate the brain and inhibit the enzyme p38-alpha. This enzyme is normally involved in regulating inflammation, but in a disease context and when chronically activated, it can have a negative impact on nerve cells’ communication by inducing excessive inflammation.

Early treatment with neflamapimod is thought to reverse synaptic dysfunction and improve brain cell health. The synapse is the junction between two nerve cells that allows them to communicate.

Researchers now evaluated neflamapimod’s ability to prevent nerve cell degeneration.

They exposed mouse neurons cultured in a lab to varying amounts of neflamapimod. Even at the lowest tested concentration, the inhibitor was able to prevent degeneration of nerve cells’ ramifications — required for proper cell-to-cell communication — triggered by toxic amyloid-beta molecules.

In addition, treatment with neflamapimod prevented the loss of cholinergic neurons — which mainly communicate with the choline acetyltransferase signaling neurotransmitter — in genetically engineered mice with Down syndrome that develop typical Alzheimer’s disease manifestations.

Specifically, treated mice showed 30% more cholinergic neurons than those treated with a placebo, maintaining nerve cell numbers similar to healthy mice and indicating that “p38α antagonism could treat the neurodegenerative process beyond reversing synaptic dysfunction,” researchers stated.

“[These] findings add to the growing body of evidence that inhibition of p38 alpha-kinase has the potential to reverse synaptic dysfunction and treat the neurodegenerative process,” John Alam, MD, president and CEO of EIP Pharma, said in a press release.

EIP Pharma is exploring the potential of neflamapimod to treat early-stage Alzheimer’s disease and dementia with Lewy bodies.

The company also recently launched a Phase 2a trial (NCT03980938) to evaluate neflamapimod as treatment for cognitive dysfunction in patients with early Huntington’s disease.

The study is recruiting participants at the United Kingdom’s John Van Geest Centre for Brain Repair, University of Cambridge. More information on enrollment can be found here.