Dr. Polydefkis is a Neurology Fellow at Johns Hopkins. He has spent the past two years training in electrophysiology and neuromuscular disease emphasizing applications of skin biopsy to evaluate small fiber nerves. Through this award, he will conduct patient oriented clinical research as a faculty member in Neurology at Johns Hopkins, pursuing skin biopsy as a novel tool to measure axonal regeneration and to screen neurotrophic agents for potential efficacy. Drs. Griffin and McArthur will comentor the candidate and are experts in the fields of peripheral nerve disease, and epidemiology and clinical trial design respectively. The candidate will also complete formal training in clinical investigation and peripheral nerve regeneration. The search for agents to promote axonal regeneration in diabetic neuropathy has been met with frustration. A pattern has emerged in which neurotrophic compounds appear promising in animal models yet fail to fulfill that promise in human trials. A consensus has emerged that novel approaches and outcome measures are needed. The purpose of this study is to develop standardized, human nerve injury models in epidermal nerve fibers. Regenerative capacity in response to these standardized nerve injuries will be developed as an outcome measure. This approach has several advantages: the biopsy technique is noninvasive, able to detect mild neuropathy and can be repeated to follow changes over time. Dr. Polydefkis has developed techniques to measure both regenerative and collateral sprouting of epidermal nerve fiber axons. Regenerative sprouting is determined through reinnervation of skin following chemical axotomy achieved by the topical application of capsaicin. Collateral sprouting is assessed by the growth of epidermal nerve fibers from the margins of a biopsy site into the healed biopsy site. These models will allow comparison of the regenerative capacity in diabetics and healthy controls. Since the reinnervation measured through our models occurs in a timely fashion, they are ideally suited to the application as novel outcome measures to assess the efficacy of neurotrophic agents in diabetic neuropathy trials. The combination of research utilizing established laboratory techniques; the excellent mentorship of senior scientists, and the supportive environment of the Johns Hopkins University will provide Dr. Polydefkis the skills he needs to develop into an independent clinician researcher in the field of peripheral nerve disease.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
Application #
Study Section
NST-2 Subcommittee (NST)
Program Officer
Porter, John D
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Johns Hopkins University
Schools of Medicine
United States
Zip Code
Hahn, K; Triolo, A; Hauer, P et al. (2007) Impaired reinnervation in HIV infection following experimental denervation. Neurology 68:1251-6
Polydefkis, M; Sirdofsky, M; Hauer, P et al. (2006) Factors influencing nerve regeneration in a trial of timcodar dimesylate. Neurology 66:259-61
Hahn, Katrin; Sirdofsky, Michael; Brown, Anna et al. (2006) Collateral sprouting of human epidermal nerve fibers following intracutaneous axotomy. J Peripher Nerv Syst 11:142-7
Zhou, Z; Hoke, A; Cornblath, D R et al. (2005) APOE epsilon4 is not a susceptibility gene in idiopathic or diabetic sensory neuropathy. Neurology 64:139-41
Gebo, Kelly A; Kalyani, Rita; Moore, Richard D et al. (2005) The incidence of, risk factors for, and sequelae of herpes zoster among HIV patients in the highly active antiretroviral therapy era. J Acquir Immune Defic Syndr 40:169-74
Polydefkis, Michael; Hauer, Peter; Sheth, Soham et al. (2004) The time course of epidermal nerve fibre regeneration: studies in normal controls and in people with diabetes, with and without neuropathy. Brain 127:1606-15
Polydefkis, Michael; Griffin, John W; McArthur, Justin (2003) New insights into diabetic polyneuropathy. JAMA 290:1371-6
Sumner, C J; Sheth, S; Griffin, J W et al. (2003) The spectrum of neuropathy in diabetes and impaired glucose tolerance. Neurology 60:108-11