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. Our drug, neflamapimod, could 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
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 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.
The scientific rationale for evaluating neflamapimod to promote recovery after stroke is that the basal forebrain cholinergic system plays a critical for recovery, particular motor function recovery, after ischemic stroke, and synaptic function that system is suppressed by residual inflammation in the weeks and months after the acute stroke event. Neflamapimod through the same mechanisms operating in DLB would be expected to reverse that suppression of basal forebrain cholinergic function, leading to improved recovery of motor function.
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.
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.
"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 dementia with Lewy bodies and other neurological disorders where synaptic dysfunction in the basal forebrain cholinergic system contributes to disease expression and progression."