Anti-NRTN (aa 178-193) polyclonal antibody

Congenital absence of pain perception is a rare phenotype. Here we report two unrelated adult individuals who have a previously unreported neuropathy consisting of congenital absence of pain with hyperhidrosis (CAPH). Both subjects had normal intelligence and productive lives despite failure to experience pain due to broken bones, severe cold or burns. Functional assessments revealed that both are generally hypesthetic with thresholds greater than two standard deviations above normal for a several of modalities in addition to noxious stimuli. Sweating was 3 to 8-fold greater than normal. Sural nerve biopsy showed that all types of myelinated and unmyelinated fibers were severely reduced. Extensive multi-antibody immunofluorescence analyses were conducted on several skin biopsies from the hands and back of one CAPH subject and two normal subjects. The CAPH subject had all normal types of immunochemically and morphologically distinct sensory and autonomic innervation to the vasculature and sweat glands, including a previously unknown cholinergic arterial innervation. Virtually all other types of normal cutaneous C, A delta and A beta-fiber endings were absent. This subject had no mutations in the genes SCN9A, SCN10A, SCN11A, NGFB, TRKA, NRTN and GFRA2. Our findings suggest three hypotheses: (1) that development or maintenance of sensory innervation to cutaneous vasculature and sweat glands may be under separate genetic control from that of all other cutaneous sensory innervation, (2) the latter innervation is preferentially vulnerable to some environmental factor, and (3) vascular and sweat gland afferents may contribute to conscious cutaneous perception. (C) 2009 Published by Elsevier B. V. on behalf of International Association for the Study of Pain.

Parkinson's disease is a progressive neurodegenerative disorder for which there is no known cure. Agents have been developed to alleviate symptoms, reduce functional disability and slow or arrest progression of the disease, resulting in a near-normal life expectancy and satisfactory quality of life. Dopaminergic agents, which are the mainstay of antiparkinsonian therapy, are effective only during the early phases of the disease and their efficacy is reduced with complications. A novel and promising approach to the treatment of Parkinson's disease is gene therapy, including viral vector-mediated transfer of candidate genes to enhance dopamine production or the survival of dopaminergic neurons. CERE-120 (AAV-hNGF-hNTN) is a novel gene therapy product that delivers a modified human neurturin (NRTN or NTN) gene (i.e., prepro sequence of human neurturin replaced with the prepro domain of human nerve growth factor beta [NGF beta]) via an adeno-associated virus type 2 (AAV2) vector under the control of the CAG promoter. CERE-120 has been shown to be efficiently secreted from human cells and to be safety delivered to target areas, exerting biological activity in vivo. Moreover, CERE-120 demonstrated promise in a phase I study in patients with Parkinson's disease.