Funded Studies
Study Rationale: Parkinson’s disease is a progressive neurodegenerative disorder; meaning that from its inception, neurons are continuously dying with resulting worsening of neurologic symptoms. Two interrelated pathological processes that contribute to neurodegeneration in Parkinson’s disease are: 1) the accumulation of toxic forms of otherwise essential proteins and 2); a maladaptive chronic activation of neuroimmune responses. Toll-like receptors (TLRs) and specifically TLRs 2 and 9 are immune modulators whose inappropriate activation maintains a neuroinflammatory state and suppresses the ability of brain cells to remove toxic proteins. Thus, it is possible that a therapeutic agent that blocks both TLR2 and TLR9 may reduce neuroinflammation and restore the brain’s ability to remove toxic proteins thereby stopping or slowing disease-progression.
Hypothesis: NPT1220-478 is a potent and selective TLR2 and TLR9 antagonist that has worked in small models of neurodegenerative disorders. However, it is not yet been determined whether it can be safely administered to humans at doses sufficient to produce therapeutic actions. Studies administered will characterize the safety, toxicity and therapeutic potential of NPT1220-478 in animals. These studies will then evaluate the safety, tolerability and pharmacokinetics, in human volunteers and ultimately patients with Parkinson’s disease.
Study Design: To further characterize the potential beneficial actions (and required blood levels) of NPT1220-478 chronic dosing studies will be conducted in small models with Parkinson’s disease to determine safety and toxicity. These studies will include measures of TLR blockade, neuroinflammation and protein pathology. In parallel, studies will be conducted using human blood to confirm the ability of NPT1220-478 to block TLRs in situ. These studies will then evaluate the safety, tolerability and pharmacokinetics, in human volunteers and ultimately patients with Parkinson’s disease.
Impact on Diagnosis/Treatment of Parkinson’s disease: These studies will determine whether NPT1220-478 can be safely administered to Parkinson’s disease patients at doses sufficient to block TLR2 and TLR9.
Next Steps for Development: If the outcome of these studies is positive, subsequent studies to measure the ability of NPT1220-578 to alter markers of disease pathology would be undertaken ultimately leading to FDA approved clinical trials to test the ability of NPT1220-478 to slow the progression of Parkinson’s disease.