Alzheimer’s Disease

Until recently, experimental therapies developed for Alzheimer’s disease largely focused on preventing the build-up of amyloid plaques to slow disease progression. EIP Pharma is charting a new course – focused on reversing the synaptic dysfunction that in the early stages, regardless of cause, underlies the memory deficits seen in Alzheimer’s.

The Role of Synaptic Dysfunction in Alzheimer’s Disease

The brain has billions of neurons, and each one connects to other neurons in the brain through synaptic connections. In the past five years, scientists have found that the synapse is a convergence point for amyloid beta, tau and inflammation, all of which have been linked to synapse toxicity and either the onset or progression of disease.

Evidence suggests that synaptic dysfunction could be the fundamental pathologic event within the neuron that causes memory deficits – the defining characteristic of the disease. Synaptic dysfunction is reversible in animal models, suggesting that therapeutics targeting synaptic dysfunction have the potential to reverse memory deficits. EIP Pharma is aiming to treat synaptic dysfunction to both slow and potentially reverse disease progression in the early stages of Alzheimer’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 protecting cells from acute injury, chronically activated p38 alpha activity within neurons can damage synapses and lead to synaptic dysfunction. If untreated, synaptic dysfunction continues to progress, resulting in the loss of neurons.

EIP Pharma is developing an oral p38 alpha inhibitor, neflamapimod, to slow or reverse synaptic dysfunction in patients with early-stage Alzheimer’s disease. We’ve conducted two phase 2a studies and one phase 2b study of neflamapimod in patients in the early stages of symptomatic Alzheimer’s disease and found that the drug potentially reverses synaptic dysfunction and improves episodic memory, or a person’s ability to create memories of new events and activities. Examples of episodic memory can include where you parked your car, where you placed your keys or whether you took your medication.

The phase 2b study to evaluate Neflamapimod in early Alzheimer’s patients was completed and results were reported at the Clinical Trials in Alzheimer’s meeting in December 2019 and further at the AAT-AD/PD Focus meeting in April 2020. In that study, neflamapimod demonstrated target engagement, with significant reduction relative to placebo in CSF p-tau and tau and also suggested that cognition was improved in patients with the highest levels of drug in their blood.

Read Next: Our Treatment & Results

"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."

John Alam, MD, EIP Pharma Founder and CEO