Pediatrics & Therapeutics
Open Access
ISSN: 2161-0665
+44 1478 350008
ISSN: 2161-0665
+44 1478 350008
H Michael Dosch
University of Toronto, Canada
Keynote: Pediat Therapeut
Our Diabetes Research Program focused on neuronal elements in T1D pathogenesis. We found that in T1D mouse models as well as patients, 1.) a major subset of autoimmune targets have neuronal derivation; 2.) TRPV1 (transient receptor potential, vanilloid- 1, a Ca++channel) mutations are a core disease-prerequisite, which consequent deficiency of TRPV1-dependent neuropeptides such as substance P (sP). Hypofunctional/hyposecretory mutations in T1D-prone NOD mice have analogs in T1D patients: human TRPV1 (chromosome 17) is polymorphic with possibly thousands of varied alleles, but we found the exclusive presence of the same, 4 alleles in over 50 patients. The sole exception was one T1D patient, carrying non-polymorphic, African TRPV1. Single nucleotide polymorphisms (SNP) Analysis of 1000-Genomes data showed 59 severe SNP mutations TRPV1(2.3%). Remarkably, there were 159 TRPV1 SNPs in our first 21 T1D patients, clustered mainly in 6 of 28 genomic PCR fragments sequenced, and this trend is sustained in 28 additional patients. Collectively, these data emphasize similarities between NOD mice and patients, with TRPV1 clearly a prominent if not the major element. T1D is reversed in NOD mice for months following a single pancreatic sP injection via the celiac artery, a routine medical access route in Interventional Image-Guided therapies (IGT). Recently, substantial reserves of pre-betacells with re-differentiation of functionality were discovered well after T1D onset. Here we describe our approved translational trial, designed to determine if and at what dose sP can reverse human T1D.
Prof. H Michael Dosch received all his schooling & training in, then, West Germany, graduating with the German MD, PhD degree in 1970 from Phillips University in Marburg/ Lahn. In 1974 he began postdoctoral training at Toronto University, Canada, joined the Faculty 1977 and was promoted to full Professor of Pediatrics and Immunology. His core interest molecular & cellular elements of (mostly) Type-1 Diabetes documented in over 500 often high profile articles.