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Neurogenetics Branch

Kenneth H. Fischbeck, M.D.

NIH Distinguished Investigator

Neurogenetics Branch
Building 35 Room 2A-1000

Bethesda MD 20892-3705
Office: (301) 435-9318
Lab: (301) 435-9288
Fax: (301) 480-3365
fischbek@ninds.nih.gov

Dr. Fischbeck received A.B. and A.M. degrees from Harvard University and an M.D. degree from Johns Hopkins. After a medical internship at Case Western Reserve University and a neurology residency at the University of California in San Francisco, he did postdoctoral research on muscular dystrophy at the University of Pennsylvania. In 1982 he joined the faculty in the Neurology Department at the University of Pennsylvania Medical School. In 1998 he came to the NINDS as Chief of the Neurogenetics Branch. He received the Cotzias Award from the American Academy of Neurology and the Jacoby Award from the American Neurological Association, and he was elected to the Institute of Medicine. His research group is identifying the causes and studying the mechanisms of hereditary neurological and neuromuscular diseases with the goal of developing effective treatment for these disorders.



The purpose of the Neurogenetics Branch is to investigate the causes of hereditary neurological diseases, with the goal of developing effective treatments for these disorders. Particular areas of research interest in the Fischbeck lab include the polyglutamine expansion diseases (Huntington's disease, Kennedy's disease, and spinocerebellar ataxia), spinal muscular atrophy, Charcot-Marie-Tooth disease, muscular dystrophy, hereditary motor neuron disease, and Friedreich's ataxia. A genetic outreach program is intended to identify and characterize patients and families with hereditary neurological diseases. The disease mechanisms are studied and potential treatments are evaluated in cell culture and other model systems. A trial of dutasteride treatment for Kennedy's disease was recently completed, and other clinical trials for Kennedy's disease and Duchenne muscular dystrophy are in progress. Efforts are also currently underway to develop new treatments for spinal muscular atrophy.



Clinical Protocol

  • A two-part placebo-controlled study to evaluate the safety, tolerability and preliminary efficacy of BVS857 in patients with spinal and bulbar muscular atrophy (SBMA) 14-N-0051

  • Clinical and molecular manifestations of inherited neurologic disorders 00-N-0043

  • Effect of functional exercise in patients with spinal and bulbar muscular atrophy 11-N-0171

  • Evaluation of skeletal muscle, cardiac, and diaphragm imaging bio-markers for GSK2402968 effects in ambulatory boys with Duchenne muscular dystrophy 11-N-0261


Staff Image
  • Eveline Arnold, Ph.D.
    Postdoctoral Fellow
    Phone :
    Email : eveline.arnold@nih.gov

  • Laura Bott
    Graduate Student
    Phone :
    Email : laura.bott@nih.gov

  • Emily Carifi, Ph.D.
    Postdoctoral Fellow
    Phone :
    Email : emily.carifi@nih.gov

  • Ke-lian Chen
    Biologist
    Phone :
    Email : chenk@mail.nih.gov

  • Derrick Fox, M.D.
    Postdoctoral Fellow
    Phone :
    Email : derrick.fox@nih.gov

  • Christopher Grunseich, M.D.
    Clinical Fellow
    Phone :
    Email : christopher.grunseich@nih.gov

  • George Harmison
    Chemist
    Phone :
    Email : harmisog@ninds.nih.gov

  • Elizabeth Hartnett
    Patient Care Coordinator
    Phone :
    Email : elizabeth.hartnett@nih.gov

  • Ilona Kats
    Postbaccalaureate IRTA
    Phone :
    Email : ilona.kats@nih.gov

  • Angela Kokkinis, R.N.
    Research Nurse
    Phone :
    Email : akokkinis@mail.nih.gov

  • Trangkimberly Nguyen
    Postbaccalaureate IRTA
    Phone :
    Email : trangkimberly.nguyen@nih.gov

  • Carlo Rinaldi, M.D.
    Visiting Fellow
    Phone :
    Email : carlo.rinaldi@nih.gov

  • Alice Schindler, M.S.
    Genetic Counselor
    Phone :
    Email : schindlerab@ninds.nih.gov

  • Rebecca Silverman
    Office Manager
    Phone :
    Email : silvermb@ninds.nih.gov

  • 1) Sangare M, Hendrickson B, Sango HA, Chen K, Nofziger J, Abdelbasset A, Dutra A, Schinder AB, Guindo A, Traore M, Harmison G, Pak E, Yaro FN, Bricceno K, Grunseich C, Chen G, Boehm M, Zukosky K, Bocoum N, Meilleur KG, Daou F, Bagayogo K, Coulibaly YI, Diakite M, Fay MP, Lee HS, Saad A, Gribaa M, Singleton AB, Maiga Y, Auh S, Landoure G, Fairhurst RM, Burnett BG, Scholl T, Fischbeck KH (2014)
  • Genetics of low spinal muscular atrophy carrier frequency in sub-Saharan Africa
  • Neurol, 75, 525-532
  • 2) Lin X, Ruiz J, Bajraktari I, Ohman R, Banerjee S, Gribble K, kaufman JD, Wingfield PT, Griggs RC, Fischbeck KH, Mankodi A (2014)
  • ZASP mutations in actin-binding domain cause disruption of skeletal muscle actin filaments in myofibrillar myopathy
  • J Biol Chem, 289, 13615-13626
  • 3) Kwon DY, Dimitriadi M, Terzic B, Cable C, Hart AC, Chitnis A, Fischbeck KH, Burnett BG (2013)
  • The E3 ubiquitin ligase mind bomb 1 ubiquitinates and promotes the degradation of survival of motor neuron protein
  • Mol Biol Cell, 24, 1863-1871
  • 4) Landoure G, Zhu P-P, Lourenco CM, Johnson JO, Toro C, Bricceno KV, Rinaldi C, Meilleur KG, Sangare M, Diallo O, Pierson TM, Ishiura H, Tsuji S, Hein N, Fink JK, Stoll M, Nicholson G, Gonzalez M, Speziani F, Durr A, Stevanin G, Biesecker LG for the NIH Intramural Sequencing Center, Accardi J, Landis DMD, Gahl WA, Traynor BJ, Marques W Jr, Zuchner S, Blackstone C, Fischbeck KH, Burnett BG (2013)
  • Hereditary spastic paraplegia type 43 (SPG43) is caused by mutation in C19orf12
  • Hum Mutat, 34, 1357-1360
  • 5) Fischbeck KH (2012)
  • Developing treatment for spinal and bulbar muscular atrophy
  • Progr Neurobiol, 99, 257-261
  • 6) Rinaldi C, Grunseich C, Sevrioukova IF, Schindler A, Horkayne-Szakaly I, Lamperti C, Landoure G, Kennerson ML, Burnett BG, Biesecker L, Ghezzi D, Zeviani M, Fischbeck KH (2012)
  • Cowchock syndrome is associated with a mutation in apoptosis-inducing factor
  • Am J Hum Genet, 91, 1095-1102
  • 7) Landoure G, Knight MA, Stanescu H, Taye AA, Shi Y, Diallo O, Johnson JO, Hernandez D, Traynor BJ, Biesecker LG, Elkahoun A, Rinaldi C, Vincent A, Willcox N, Kleta R, Fischbeck KH, Burnett BG (2012)
  • A candidate gene for autoimmune myasthenia gravis
  • Neurology, 79, 342-345
  • 8) Bricceno KV, Sampognaro PJ, Van Meerbeke JP, Sumner CJ, Fischbeck KH, Burnett BG (2012)
  • Histone deacetylase inhibition suppresses myogenin-dependent atrogene activation in spinal muscular atrophy mice
  • Hum Mol Genet, 21, 4448-4459
  • 9) Rinaldi C, Bott LC, Chen K, Harmison GG, Pennuto M, Fischbeck KH (2012)
  • IGF-1 administration ameliorates disease manifestations in a mouse model of spinal and bulbar muscular atrophy
  • Mol Med, 18, 1261-1268
  • 10) Bricceno K, Fischbeck K, Burnett B (2012)
  • Neurogenic and myogenic contributions to hereditary motor neuron disease
  • Neurodegener Dis., 9, 199-209
  • 11) Motley WW, Seburn KL, Nawaz MH, Miers KE, Cheng J, Antonellis A, Green ED, Talbot K, Yang XL, Fischbeck KH, Burgess RW (2011)
  • Charcot-Marie-Tooth-linked mutant GARS is toxic to peripheral neurons independent of wild type GARS levels
  • PLoS Genet. , 7, e1002399
  • 12) Kwon DY, Motley WW, Fischbeck KH, Burnett BG (2011)
  • Increasing expression and decreasing degradation of SMN ameliorate the spinal muscular atrophy phenotype in mice
  • Hum Molec Genet , 20, 3667-3677
  • 13) Fernandez-Rhodes LE, Kokkinis AD, White MJ, Watts CA, Auh S, Jeffries NO, Shrader JA, Lehky TJ, Li L, Ryder JE, Levy EW, Solomon BI, Harris-Love MO, La Pean A, Schindler AB, Chen CJ, Di Prospero NA, Fischbeck KH (2011)
  • Efficacy and safety of dutasteride in patients with spinal and bulbar muscular atrophy: a randomised placebo-controlled trial
  • Lancet Neurol , 10, 140-147
  • 14) Ranganathan S, Fischbeck KH (2010)
  • Therapeutic approaches to spinal and bulbar muscular atrophy
  • Trends Pharmacol Sci , 31, 523-527
  • 15) Motley WW, Talbot K, Fischbeck KH (2010)
  • GARS axonopathy: not every neuron's cup of tRNA
  • Trends Neurosci , 33, 59-66
  • 16) Palazzolo I, Nedelsky NB, Askew CE, Harmison GG, Kasantsev AG, Taylor JP, Fischbeck KH, Pennuto M (2010)
  • B2 attenuates polyglutamine-expanded androgen receptor toxicity in cell and fly models of spinal and bulbar muscular atrophy
  • J Neurosci Res , 88, 2207-2216
  • 17) Landoure G, Zdebik AA, Martinez TL, Burnett BG, Stanescu HC, Inada H, Shi Y, Taye AA, Kong L, Munns CH, Choo SS, Phelps CB, Paudel R, Houlden H, Ludlow CL, Caterina MJ, Gaudet R, Kleta R, Fischbeck KH, Sumner CJ (2010)
  • Mutations in TRPV4 cause Charcot-Marie-Tooth disease type 2C
  • Nature Genet , 42, 170-174
  • 18) Meilleur KG, Traore M, Sangare M, Britton A, Landoure G, Coulibaly S, Niare B, Mochel F, La Pean A, Rafferty I, Watts C, Shriner D, Littleton-Kearney MT, Blackstone C, Singleton A, Fischbeck KH (2010)
  • Hereditary spastic paraplegia and amyotrophy associated with a novel locus on chromosome 19
  • Neurogenetics, 11, 313-318
  • 19) Rhodes LE, Freeman BK, Auh S, Kokkinis AD, La Pean A, Chen C, Lehky TJ, Schrader JA, Levy EW, Harris-Love M, Di Prospero NA, Fischbeck KH (2009)
  • Clinical features of spinal and bulbar muscular atrophy
  • Brain, 132, 3242-3251
  • 20) Burnett BG, Munoz E, Tandon A, Kwon D, Sumner CJ, Fischbeck KH (2009)
  • Regulation of SMN protein stability
  • Mol Cell Biol, 29, 1107-1115
  • 21) Ranganathan S, Harmison GG, Meyertholen K, Pennuto M, Burnett BG, Fischbeck KH (2009)
  • Mitochondrial abnormalities in spinal and bulbar muscular atrophy
  • Hum Molec Genet, 18, 27-42
  • 22) Traore M, Landoure G, Motley W, Sangare M, Meilleur K, Coulibaly S, Traore S, Niare B, Mochel F, La Pean A, Vortmeyer A, Mani H, Fischbeck KH (2009)
  • Novel mutation in the NHLRC1 gene in a Malian family with a severe phenotype of Lafora disease
  • Neurogenetics , 10, 319-323
  • 23) Palazzolo I, Stack C, Kong L, Musaro A, Adachi H, Katsuno M, Sobue G, Taylor JP, Sumner CJ, Fischbeck KH, Pennuto M (2009)
  • Overexpression of IGF-1 in muscle attenuates disease in a mouse model of spinal and bulbar muscular atrophy
  • Neuron, 63, 316-328
  • 24) Knight MA, Hernandez D, Diede SJ, Dauwerse HG, Rafferty I, van de Leemput J, Forrest SM, Gardner RJM, Storey E, van Ommen GJ, Tapscott SJ, Fischbeck KH, Singleton AB (2008)
  • A duplication at chromosome 11q12.2-11q12.3 is associated with spinocerebellar ataxia type 20
  • Hum Molec Genet, 17, 3847-3853
  • 25) Mochel F, Knight MA, Tong WH, Hernandez D, Ayyad K, Taivassalo T, Andersen PM, Singleton A, Rouault TA, Fischbeck KH, Haller RG (2008)
  • Splice mutation in the iron-sulfur cluster scaffold protein ISCU causes myopathy with exercise intolerance
  • Am J Hum Genet, 82, 652-660
  • 26) Burnett BG, Andrews J, Ranganathan S, Fischbeck KH, Di Prospero NA (2008)
  • Expression of expanded polyglutamine targets profilin for degradation and alters actin dynamics
  • Neurobiol Disease, 30, 365-374
  • 27) Di Prospero NA, Baker A, Jeffries N, Fischbeck KH (2007)
  • Neurological effects of high-dose idebenone in patients with Friedreich's ataxia: a randomised, placebo-controlled trial
  • Lancet Neurology, 6, 878-886
  • 28) Di Prospero NA, Sumner CJ, Penzak SR, Ravina B, Fischbeck KH, Taylor JP (2007)
  • Safety, tolerability, and pharmacokinetics of high-dose idebenone in patients with Friedreich's ataxia
  • Arch Neurol, 64, 803-808
  • 29) Palazzolo, I., Burnett, B.G., Young, J.E., Brenne, P.L., La Spada, A.R., Fischbeck, K.H., Howell, B.W., Pennuto, M. (2007)
  • Akt blocks ligand binding and protects against expanded polyglutamine androgen receptor toxicity
  • Hum. Mol. Genet., 16, 1593-1603
  • 30) Avila AM, Burnett BG, Taye AA, Gabanella F, Knight MA, Hartenstein P, Cizman Z, DiProspero NA, Pellizoni L, Fischbeck KH, Sumner CJ (2007)
  • Trichostatin A increases SMN expression and survival in a mouse model of spinal muscular atrophy
  • J Clin Invest , 117, 659-671
  • 31) Levy JR, Sumner CJ, Caviston JP, Tokito MK, Ranganathan S, Ligon LA, Wallace KE, LaMonte BH, Harmison GG, Puls I, Fischbeck KH, Holzbaur EL (2006)
  • A motor neuron disease-associated mutation in p150 perturbs dynactin function and induces protein aggregation
  • J Cell Biol, 172, 733-745
  • 32) Sumner CJ, Kolb SJ, Harmison GG, Jeffries NO, Schadt K, Finkel RS, Dreyfuss G, Fischbeck KH (2006)
  • SMN mRNA and protein levels in the peripheral blood: Biomarkers for SMA clinical trials
  • Neurology, 66, 1067-1073
  • 33) Sivakumar K, Kyriakides T, Puls I, Nicholson GA, Funalot B, Antonellis A, Sambuughin N, Christodoulou K, Beggs JL, Zamba-Papanicolaou E, Ionasescu V, Dalakas MC, Green ED, Fischbeck KH, Goldfarb LG (2005)
  • Phenotypic spectrum of disorders associated with glycyl-tRNA synthetase mutations
  • Brain, 128, 2304-2314
  • 34) Di Prospero NA, Fischbeck KH (2005)
  • Therapeutics development for triplet repeat expansion diseases
  • Nature Rev Genet, 6, 756-765
  • 35) Verbeek DS, Knight MA, Harmison GG, Fischbeck KH, Howell BW (2005)
  • Spinocerebellar ataxia 14 mutations in protein kinase C gamma increase activity and alter membrane targeting
  • Brain, 128, 436-442
  • 36) Liang GSL, de Miguel M, Gomez-Hernandez JM, Glass JD, Scherer SS, Barrio LC, Fischbeck KH (2005)
  • Severe neuropathy with leaky connexin32 hemichannels
  • Ann Neurol, 57, 749-754
  • 37) Puls I, Oh SJ, Sumner C, Wallace KE, Floeter MK, Mann EA, Kennedy WR, Wendelschafer-Crabb G, Vortmeyer A, Powers R, Finnegan K, Holzbaur ELF, Fischbeck KH, Ludlow CL (2005)
  • Distal spinal and bulbar muscular atrophy caused by dynactin mutation
  • Ann Neurol, 57, 687-694
  • 38) Kernochan LE, Russo ML, Woodling NS, Huynh TN, Avila A, Fischbeck KH, Sumner CJ (2005)
  • The role of histone acetylation in SMN gene expression
  • Hum Molec Genet, 14, 1171-1182
  • 39) Piccioni F, Roman BR, Fischbeck KH, Taylor JP (2004)
  • A screen for drugs that protect against the cytotoxicity of polyglutamine-expanded androgen receptor
  • Hum Molec Genet , 13, 437-446
  • 40) Chen YZ, Bennett CL, Huynh HM, Blair IP, Puls I, Irobi J, Dierick I, Abel A, Kennerson ML, Rabin BA, Nicholson GA, Auer-Grumbach M, Wagner K, De Jonghe P, Griffin JW, Fischbeck KH, Timmerman V, Cornblath DR, Chance PF (2004)
  • DNA/RNA helicase gene mutations in a form of juvenile amyotrophic lateral sclerosis (ALS4)
  • Am J Hum Genet , 74, 1128-1135
  • 41) Taylor JP, Taye AA, Campbell C, Kazemi-Esfarjani P, Fischbeck KH, Min KT (2003)
  • Aberrant histone acetylation, altered transcription, and retinal degeneration in a Drosophila model of polyglutamine disease are rescued by CREB-binding protein
  • Genes Devel , 17, 1463-1468
  • 42) Antonellis A, Ellsworth RE, Sambuughin N, Puls I, Abel A, Lee-Lin SQ, Jordanova A, Kremensky I, Christadoulou K, Middleton LT, Sivakumar K, Ionasescu V, Funalot B, Vance JM, Goldfarb LG, Fischbeck KH, Green ED (2003)
  • Glycyl tRNA synthetase mutations are responsible for Charcot-Marie-Tooth disease type 2D and distal spinal muscular atrophy type V
  • Am J Hum Genet , 72, 1293-1299
  • 43) Puls I, Jonnakuty C, LaMonte BH, Holzbaur ELF, Tokito M, Mann E, Floeter MK, Bidus K, Drayna D, Oh SJ, Brown RH, Ludlow CL, Fischbeck KH (2003)
  • Mutant dynactin in motor neuron disease
  • Nature Genet, 33, 455-456
  • 44) Sumner CJ, Huynh TN, Markowitz JA, Perhac JS, Hill B, Coovert DD, Schussler K, Chen X, Jarecki J, Burghes AHM, Taylor JP, Fischbeck KH (2003)
  • Valproic acid increases SMN levels in spinal muscular atrophy patient-derived cell lines
  • Ann Neurol, 54, 647-654
  • 45) Taylor JP, Hardy J, Fischbeck KH (2002)
  • Toxic proteins in neurodegenerative disease
  • Science , 296, 1991-1995
  • 46) Taylor JP, Fischbeck KH (2002)
  • Altered acetylation in polyglutamine disease: an opportunity for therapeutic intervention?
  • Trends Molec Med , 8, 195-197
  • 47) Hara H, Nolan PM, Scott MO, Bucan M, Wakayama Y, Fischbeck KH (2002)
  • Running endurance abnormality in mdx mice
  • Muscle Nerve , 25, 207-211
  • 48) Caplen NJ, Taylor JP, Statham VS, Tanaka F, Fire AW, Morgan RA (2002)
  • Rescue of polyglutamine mediated cytotoxicity by double stranded RNA mediated RNA interference
  • Hum Molec Genet, 11, 175-184
  • 49) Lieberman AP, Harmison G, Strand AD, Olson JM, Fischbeck KH (2002)
  • Altered transcriptional regulation in cells expressing the expanded polyglutamine androgen receptor
  • Hum Molec Genet , 11, 1967-1976
  • 50) Wagner KR, Hamed SA, Hadley DW, Gropman AL, Burstein AH, Escolar D, Hoffman EP, Fischbeck KH (2001)
  • Gentamicin treatment of Duchenne and Becker muscular dystrophy due to nonsense mutations
  • Ann Neurol , 49, 706-711
  • 51) McCampbell A, Taye AA, Whitty L, Penney E, Steffan JS, Fischbeck KH (2001)
  • Histone deacetylase inhibitors reduce polyglutamine toxicity
  • Proc Natl Acad Sci USA , 98, 15179-15184
  • 52) Fischbeck KH (2001)
  • Polyglutamine expansion neurodegenerative disease
  • Brain Res Bull, 56, 161-163
  • 53) McCampbell A, Fischbeck KH (2001)
  • Polyglutamine and CBP: Fatal attraction?
  • Nature Med , 7, 528-530
  • 54) Lieberman AP, Puls I, Fischbeck KH (2001)
  • Mining the genome for causes and cures of neurologic disease
  • Trends Pharmacol Sci , 22, 161-162
  • 55) McCampbell A, Taylor JP, Taye AA, Robitschek J, Li M, Walcott J, Merry D, Sobue G, Fischbeck KH (2000)
  • CREB-binding protein sequestration by expanded polyglutamine
  • Hum Molec Genet , 9, 2197-2202
  • 56) Fischbeck KH, Lieberman A, Bailey CK, Abel A, Merry DE (1999)
  • Androgen receptor mutation in Kennedy's disease
  • Phil Trans R Soc Lond, 354, 1075-1078
  • 57) Warrick JM, Paulson HL, Gray-Board GL, Bui QT, Fischbeck KH, Pittman RN, Bonini NM (1998)
  • Expanded polyglutamine protein forms nuclear inclusions and causes neural degeneration in Drosophila
  • Cell, 93, 939-949
  • 58) Merry DE, Kobayashi Y, Bailey CK, Taye AA, Fischbeck KH (1998)
  • Cleavage, aggregation and toxicity of the expanded androgen receptor in spinal and bulbar muscular atrophy
  • Hum Molec Genet, 7, 693-701

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