Stroke, caused by blockage of arteries supplying blood to the brain, is the number one cause of long-term disability in adults. Most stroke survivors have some level of recovery after a stroke. However, in moderately severe and severe stroke the recovery is often incomplete, even with physical rehabilitative therapy. Currently there is no approved pharmacological therapy to improve recovery beyond what is achieved with rehabilitation. EIP Pharma is developing a drug, neflamapimod, to reverse the synaptic dysfunction and improve the neural and synaptic plasticity within the brain that is required for optimal recovery after stroke.
The Role of Synaptic Dysfunction in Stroke Recovery
The brain has billions of neurons, and each one connects to other neurons in the brain through synaptic connections. Efficient synaptic function is essential for establishing new neuronal connections during the recovery process. Persistent inflammation after moderately severe and severe stroke inhibits synaptic function, i.e., induces synaptic dysfunction, resulting in impaired functional recovery.
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 lead to synaptic dysfunction. If untreated, synaptic dysfunction will progress and result in neuron loss.
EIP Pharma is developing an oral p38 alpha inhibitor, neﬂamapimod, to reverse synaptic dysfunction and promote recovery after stroke. In a published preclinical study neflamapimod treatment for six weeks starting two days after acute experimental stroke induction significantly improved, relative to vehicle treated control animals, neurological function.
Administration of a p38α inhibitor after transient ischemia-induced stroke in the rat promotes dose-dependent functional recovery
Resources for Patients and Caregivers
MORE ABOUT THE DISEASELewy Body Dementia Association (LBDA)
Alzheimer's Association: Lewy Body Dementia
National Institute on Aging (NIH)
EXPANDED ACCESSExpanded Access Policy
SUPPORT GROUPSLBDA: Caregiver Packet
Well Spouse Association
QUESTIONS ABOUT EIP'S APPROACHLearn more about our unique approach to reversing the effects of dementia with Lewy bodies
Ask us a question
"Often when people think of neurodegeneration they look toward the end of the process, which is characterized by neuron death and loss. But in fact, neurodegeneration is a long and complex process that we now know much of the time ahead of neuron death is driven by synaptic dysfunction and deterioration in a broad range of neurodegenerative diseases. In animal models, we and others have shown that if you treat synaptic dysfunction at the early stages of disease, you’re able to restore synaptic function and prevent neuron death, giving us new hope and optimism for treating not only Alzheimer’s disease, but other neurodegenerative disorders where there have been few successful treatment options."