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. Patients with DLB incur higher healthcare costs, have longer hospitalizations, report lower quality of life, and have caregivers with higher levels of distress when compared with patients with AD at similar stages of disease. There are no treatments for DLB that have been approved by the US FDA or European Medicines Agency. EIP Pharma is developing a drug, neflamapimod, to reverse and potentially slow the synaptic dysfunction that contributes to this neurological decline. Results from a phase 2 study showed that neflamapimod improves cognitive function in patients with mild to moderate DLB.
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. In DLB, the synaptic dysfunction that is responsible for symptoms occurs in a specific part of the brain called the basal forebrain and impacts a specific type of nerve called cholinergic neurons. The resulting cholinergic dysfunction then is thought to cause the decline in attention, judgement, reasoning and other symptoms associated with DLB, including mobility impairment. Synaptic dysfunction in the basal forebrain is reversible in animal models, suggesting that therapeutics targeting basal forebrain cholinergic dysfunction have the potential to reverse the cognitive and motor 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 in 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. In animal studies, neflamapimod reverses disease progression and increases the number of cholinergic neurons in the basal forebrain, findings that suggest that neflamapimod has disease-modifying potential in DLB. A phase 2 clinical study aimed at evaluating neflamapimod in improving cognition in patients with mild-to-moderate DLB has recently been completed and the results indicate that neflamapimod has a significant and clinically meaningful positive effect on cognition and functional mobility in patients with mild to moderate DLB. Initial results from this trial were presented at the Clinical Trials in Alzheimer’s (CTAD) meeting in November 2020 and final results at CTAD in November 2021.
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
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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."