H Michael Dosch
University of Toronto, Canada
Title: Type 1 Diabetes (T1D) reversal by neuropeptide therapy– A Phase-1 progress report
Biography
Biography: H Michael Dosch
Abstract
Our Diabetes Research Program focused on neuronal elements in T1D pathogenesis. We found that in T1D mouse models as wellrnas patients, 1.) a major subset of autoimmune targets have neuronal derivation; 2.) TRPV1 (transient receptor potential, vanilloid-rn1, a Ca++channel) mutations are a core disease-prerequisite, which consequent deficiency of TRPV1-dependent neuropeptidesrnsuch as substance P (sP). Hypofunctional/hyposecretory mutations in T1D-prone NOD mice have analogs in T1D patients: humanrnTRPV1 (chromosome 17) is polymorphic with possibly thousands of varied alleles, but we found the exclusive presence of the same,rn4 alleles in over 50 patients. Th e sole exception was one T1D patient, carrying non-polymorphic, African TRPV1. Single nucleotidernpolymorphisms (SNP) Analysis of 1000-Genomes data showed 59 severe SNP mutations TRPV1(2.3%). Remarkably, there were 159rnTRPV1 SNPs in our fi rst 21 T1D patients, clustered mainly in 6 of 28 genomic PCR fragments sequenced, and this trend is sustainedrnin 28 additional patients. Collectively, these data emphasize similarities between NOD mice and patients, with TRPV1 clearly arnprominent if not the major element. T1D is reversed in NOD mice for months following a single pancreatic sP injection via the celiacrnartery, a routine medical access route in Interventional Image-Guided therapies (IGT). Recently, substantial reserves of pre-betacellsrnwith re-diff erentiation of functionality were discovered well aft er T1D onset. Here we describe our approved translational trial,redesigned to determine if and at what doses can reverse human T1D.