Huntington’s disease is an inherited neurological disorder that results in the death of brain cells over time. Patients with Huntington’s experience gradual physical and mental deterioration as they age, and there is currently no cure. EIP Pharma is developing a drug, neflamapimod, to reverse the synaptic dysfunction that contributes to the progressive cognitive decline that is generally the first clinical manifestation of the disease.
The Role of Synaptic Dysfunction in Huntington’s Disease
The brain has billions of neurons, and each one connects to other neurons in the brain through synaptic connections. While Huntington’s disease affects the entire brain, emerging evidence has shown that cognitive defects in the early stages of disease might originate in the neurons of hippocampus, an area of the brain that plays a crucial role in learning and memory.
Synaptic dysfunction within hippocampal neurons can lead to neuron loss, resulting in cognitive deficits that gradually worsen. Synaptic dysfunction is reversible in animal models, suggesting that therapeutics targeting synaptic dysfunction have the potential to reverse the cognitive deficits associated with early-stage Huntington’s disease.
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 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 improve the cognitive deficits associated with early-stage Huntington’s disease. A phase 2a study evaluating neflamapimod in improving cognitive deficits in patients with early-stage Huntington’s disease was started in late 2019, but has been discontinued because COVID19 restrictions at the study site impeded the completion of this study.
Resources for Patients and Caregivers
MORE ABOUT THE DISEASEHuntington’s Disease Society of America (HDSA)
National Organization for Rare Disorders (NORD)
Hereditary Disease Foundation
National Institute of Neurological Disorders and Stroke (NIH)
EXPANDED ACCESSExpanded Access Policy
SUPPORT GROUPSNDSA's Caregiver Guide for HD Families
Well Spouse Association
QUESTIONS ABOUT EIPS APPROACHLearn more about our unique approach to reversing the effects of Huntington's Disease
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"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."