Neuromuscular Disease Center

URMC Neurology Research

Scope of Research: Therapeutic Trials, Pathophysiology, Animal and Cellular Models of Disease, Molecular Genetic Alterations, Pathomechanisms and Identification of New Treatments of Neuromuscular Diseases

Goals are to understand the molecular pathology and its relationship to the metabolic alterations that cause the manifestations of each disease and to develop more rational approaches to their treatment.

• Therapeutic trials in Myotonic Dystrophy, Myotonic Dystrophy (Type 1 and Type 2), Facioscapulohumeral Dystrophy, Inclusion Body Myositis, Myasthenia Gravis, Duchenne Dystrophy, Limb Girdle Muscular Dystrophies, Non-Dystrophic Myotonic disorders, Periodic Paralysis, Charcot-Marie-Tooth disease and Amyotrophic Lateral Sclerosis.

• Clinical pathophysiology of: a) myotonia; b) muscle wasting in Myotonic Dystrophy (Types 1 and 2) and Facioscapulohumeral Muscular dystrophy; c) corticosteroid beneficial and toxic effects in Duchenne dystrophy; d) cognitive-personality changes and sleep alterations in Myotonic Dystrophy (Types 1 and 2); e) muscle pain in Myotonic Dystrophy (Types 1 and 2) and Facioscapulohumeral muscular Dystrophy; f) Small Fiber Neuropathies; and g) Charcot-Marie-Tooth disease.

• Animal and Cellular Models of: a) Myotonic dystrophy Type 1; b) oculopharyngeal muscular dystrophy; and c) in development is animal model of myotonic dystrophy Type 2.

• Pathomechanisms and Identification of treatments for: a) myotonic dystrophy type 1 using cell culture systems to screen for molecular alterations that disappear with specific drugs in the media; b) myotonic dystrophy type 1 and Facioscapulohumeral muscular dystrophy using gene chip studies of gene expression in muscle biopsy specimens; and c) myotonic dystrophy type 1 and oculopharyngeal muscular dystrophy using mouse models of these disorders to examine alterations in specific target tissues (the characteristic muscles involved; brain; heart; lens).

• Electrodiagnostic and histologic features and treatment outcome of various neuropathies, particularly Charcot-Marie-Tooth disease, selected small fiber polyneuropathies, acute and chronic inflammatory demyelinative polyneuropathy, and other hereditary polyneuropathies.

Scaled-down genetic analysis of myotonic dystrophy type 1 and type 2.
Nakamori M, Sobczak K, Moxley RT 3rd, Thornton CA
Neuromuscul Disord. 2009 Aug 25. View PubMed Reference

Reversal of RNA dominance by displacement of protein sequestered on triplet repeat RNA.
Wheeler TM, Sobczak K, Lueck JD, Osborne RJ, Lin X, Dirksen RT, Thornton CA.
Science 2009 Jul 17; 325(5938):336-9. View PubMed Reference

Transcriptional and post-transcriptional impact of toxic RNA in myotonic dystrophy.
Osborne RJ, Lin X, Welle S, Sobczak K, O’Rourke JR, Swanson MS, Thornton CA.
Hum Mol Genet. 2009 Apr 15; 18(8):1471-81. Epub 2009 Feb. 17. View PubMed Reference

Subcutaneous IGF-1 is not beneficial in 2-year ALS trail.
Sorenson EJ, Windbank AJ, Mandrekar JN, Bamlet WR, Appel SH, Armon C, Barkhaus PE, Bosch P, Boylan K, David WS, Feldman E, Glass J, Gutmann L, Katz J, King W, Luciano CA, McCluskey LF, Nash S, Newman DS, Pascuzzi RM, Pioro E, Sams LJ, Scelsa S, Simpson EP, Subramony SH, Tiryaki E, Thornton CA
Neurology. 2008 Nov 25; 71 (22):1770-5. View PubMed Reference

The hypocretin neurotransmission system in myotonic dystrophy type 1.
Ciafaloni E, Mignot E, Sansone V, Hilbert JE, Lin L, Lin X, Liu LC, Pigeon WR, Perlis ML, Thornton CA. Neurology. 2008 Jan 15; 70(3):226-30. View PubMed Reference

Common epigenetic changes of D4Z4 in contraction-dependent and contraction-independent FSHD.
De Greef JC, Lemmers RJ, van Engelen BG, Sacconi S, Venance SL, Frants RR, Tawil R, van der Maarel SM> Hum Mutat. 2009 Jul 14. View PubMed Reference

Relation between extent of myostatin depletion and muscle growth in mature mice.
Welle S, Burgess K, Thornton CA, Tawil R.
Am J Physiol Endocrinol Metab. 2009 Aug 4. View PubMed Reference

RNA transcripts, miRNA-sized fragments and proteins produced from D4Z4 units: new candidates for the pathophysiology of Facioscapulohumeral dystrophy.
Snider L, Asawachaicharn A, Tyler AE, Geng LN, Petek LM, Maves L, Miller DG, Lemmers RJ, Winokur ST, Tawil R, van der Maarel SM, Filippova GN, Tapscott SJ.
Hum Mol Genet. 2009 Jul 1: 18(13):2414-30. Epub 2009 Apr 9. View PubMed Reference

Facioscapulohumeral muscular dystrophy.
Tawil R.
Neurotherapeutics. 2008 Oct; 5 (4):601-6. Review. View PubMed Reference

Delayed diagnosis in Duchenne muscular dystrophy: data from the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet).
Ciafaloni E. Fox DJ, Pandya S, Westfield CP, Puzhankara S, Romitti PA, Mathews KD, Miller TM, Matthews DJ, Miller LA, Cunniff C, Druschel CM, Moxley RT.
J Pediatr. 2009 Sep; 155(3):380-5. Epub 2009 Apr 25. View PubMed Reference

Mycophenolate mofetil for myasthenia gravis: a clear and present controversy.
Heatwole C, Ciafaloni E.
Neuropsychiatr Dis Treat. 2008 Dec; 4(6):1203-9. View PubMed Reference

Practice parameter: the evaluation of distal symmetric polyneuropathy: the role of laboratory and genetic testing (an evidence-based review.
England JD, Gronseth GS, Franklin G, Carter GT, Kinsella LJ, Cohen JA, Asbury AK, Szigeti K, Lupski JR, Latov N, Lewis RA, Low PA, Fisher MA, Herrmann DN, Howard JF, Lauria G, Miller RG, Polydefkis M, Sumner AJ. PM R. 2009 Jan; 1(1):5-13. View PubMed Reference

Pulsed electromagnetic fields to reduce diabetic neuropathic pain and stimulate neuronal repair: a randomized controlled trial. Weintraub MI, Herrmann DN, Smith AG, Backonja MM, Cole SP. Arch Phys Med Rehabil. 2009 Jul; 90(7):1102-9 View PubMed Reference

Noninvasive and minimally invasive detection and monitoring of peripheral neuropathies.
Herrmann DN. Expert Rev Neurother. 2008 Dec; 8(12):1807-16. View PubMed Reference

Evoked myotonia can be “dialed-up” by increasing stimulus train length in myotonic dystrophy type 1.
Logigian EL, Twydell P, Dilek N, Martens WB, Quinn C, Weigner AW, Heatwole CR, Thornton CA, Moxley RT 3rd. Muscle Nerve. 2009 Sep 11. View PubMed Reference

Yield of the sural/radial ratio versus the medial plantar nerve in sensory neuropathies with a normal sural response.
Sullivan JP, Logigian EL, Kocharian N, Herrrmann DN.
J Clin Neurophysiol. 2008 Apr; 25(2):111-4. View PubMed Reference

Computerized hand grip Myometry reliably measures myotonia and muscle strength in myotonic dystrophy (DM1).
Moxley RT 3rd, Logigian EL, Martens WB, Annis CL, Pandya S, Moxley RT 4th, Barbieri CA, Dilek N, Wiegner AW, Thornton CA. Muscle Nerve. 2007 Sep; 36(3):320-8. View PubMed Reference

Richard T. Moxley, III, M.D.
Director, Neuromuscular Disease Center
(585) 275-5006

Eric L. Logigian, M.D.
Unit Chief, Neuromuscular Disease Center
(585) 275-4568

Emma Ciafaloni, M.D.
Neuromuscular Medicine Program Director
(585) 275-5006