University of Nebraska Medical Center and Longevity Biotech researchers demonstrated that LBT-3627, a novel drug candidate developed by the company, prevented nerve cell damage and protected dopamine-producing cells in a mouse model of Parkinson’s disease. The research paper, entitled “Selective VIP Receptor Agonists Facilitate Immune Transformation for Dopaminergic Neuroprotection in MPTP-Intoxicated Mice,” was published in the Journal of Neuroscience.
Faulty dopamine production is one of the hallmarks of Parkinson’s Disease (PD) and has been the focus of a substantial portion of PD research. Vasoactive intestinal peptide (VIP) is responsible for the mediation of a series of biological responses. Through the activation of two receptors, VIP receptor 1 and 2 (VIPR1 and VIPR2), the peptide is known to induce neuroprotection. Despite this, its rapid metabolism and inability to distinguish between the two receptors make the clinical application of this hormone limited.
Researchers developed a series of specific agonists for these receptors and looked into their ability to stop or protect against neurodegeneration in mice models of PD. One of these candidate molecules, LBT-3627, was found to specifically target VIPR2 with improved durability and elicited immune transformation, leading to the production of a specific subset of white blood cells that prevent damage to dopamine producing nerve cells. Importantly, the team demonstrated that LBT-3627 could achieve up to 80% protection of dopamine-producing nerve cells in these animals. Halted brain damage was attributed to microglia cells, also affected by the immune transformation observed after treatment.
Dr. Howard Gendelman, M.D., the Margaret R. Larson Professor and chair of the UNMC Department of Pharmacology and Experimental Neuroscience, commented in a press release, “The idea was birthed nearly a decade ago when specific types of circulating blood cells called lymphocytes were found to damage the types of nerve cells responsible for disease. The new Longevity Biotech drug (LBT-3627) was able to change the function of these cells from killing the nerve cells to protecting them. This is especially significant for the Nebraska team, as the mechanism parallels closely the human trials nearing completion for Parkinson’s patients.”
Future plans include progression of the drug candidate through a development phase and, in 2017, the initiation of a Phase I clinical trial.
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