Dementia with Lewy Bodies

Dementia with Lewy bodies (DLB) is a progressive disease and one of the most common types of dementia after Alzheimer’s disease. In this disease, a protein known as alpha-synuclein builds up to form structures called Lewy bodies within the neurons in the parts of the brain that control cognition, behavior and movement. The symptoms of DLB can closely resemble those from other neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. EIP Pharma is developing a drug, neflamapimod, to slow or reverse the synaptic dysfunction that contributes to this neurological decline.

The Role of Synaptic Dysfunction in Dementia with Lewy Bodies

The brain has billions of neurons, and each one connects to other neurons in the brain through synaptic connections. Evidence suggests that synaptic dysfunction results from a combination of excessive inflammation and the toxicity of alpha synuclein. The synaptic dysfunction then is thought to cause the decline in attention, judgement, reasoning and other cognitive impairments associated with DLB. Synaptic dysfunction is reversible in animal models, suggesting that therapeutics targeting synaptic dysfunction have the potential to reverse the cognitive impairments in DLB.

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 protecting cells from acute injury, chronically activated p38 alpha activity within neurons can damage synapses and contribute to alpha-synuclein-associated toxicity. 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 DLB. A phase 2 study aimed at evaluating neflamapimod in improving cognition in patients with mild-to-moderate DLB opened in July 2019 and is currently recruiting patients. Data from the study are expected to be available in the second half of 2020.

Learn more about this trial at Clinicaltrials.gov.

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