Louise Rodino-Klapac, PhD :: Nationwide Children's Hospital, Columbus, Ohio

Louise Rodino-Klapac, Ph.D.

Louise  Rodino-Klapac, Ph.D.

Center for Gene Therapy
Principal Investigator

Neurology Residency
Faculty

Neuromuscular Disorders
Principal Investigator

Contact Information

The Research Institute at Nationwide Children's Hospital
700 Children's Drive
Columbus, Ohio 43205 [ map ]
PH: (614) 722.2678
FX: (614) 722.3273
E-mail Me

Biography

Louise R. Rodino-Klapac, Ph.D is a Principal Investigator in the Center for Gene Therapy at The Research Institute at Nationwide Children’s Hospital and Assistant Professor in the Department of Pediatrics at The Ohio State University College of Medicine. Dr. Rodino-Klapac’s translational research program focuses on developing adeno-associated viral vectors to treat both Duchenne and Limb Girdle muscular dystrophies.

Gender:

  • Female

Languages Spoken:

  • English

Research Interests

Research Center:

Areas of Interest:

  • My laboratory is focused on developing gene therapy based vectors for the treatment of neuromuscular disorders. With emphasis on translating laboratory benchside research to the bedside, we are optimizing gene replacement strategies for Duchenne muscular dystrophy (DMD) and several recessive forms of Limb Girdle Muscular Dystrophy (LGMD). A universal treatment goal among all these disorders is delivering recombinant adeno-associated virus (rAAV) mediated vectors by a vascular route to target multiple muscle groups. We are poised to begin clinical trials for LDMD2D [alpha-sarcoglycan (SGCA) deficiency] and micro-dystrophin DMD using this approach. In the pre-clinical stage we are developing gene therapy based therapeutics for LGMD2E [beta-sarcoglycan (SGCB) deficiency] and LGMD2B [dysferlin (DYSF) deficiency]. For DYSF deficiency we have developed a novel approach using two vectors that recombine in muscle to deliver the entire dysferlin gene. We have robust pre-clinical date using this approach and are currently focused on translating these studies to the clinic.

    Our vascular delivery work for DMD has been funded by Jesse’s Journey and our Dysferlin Gene Therapy development has been funded by the Jain Foundation.

    Links to our funding agencies and recent publications can be found on our Facebook Page.

Education and Training

Undergraduate School

  • Kings College
    Date Completed: 06/30/2000

Post Doctoral

  • The Ohio State University
    Date Completed: 06/30/2005

Fellowship

  • The Research Institute at Nationwide Children's Hospital
    Date Completed: 06/30/2005

Professional Experience

2010–present

  • Principal Investigator, Center for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, OH

2010–present

  • Assistant Professor of Pediatrics, The Ohio State University, The Research Institute at Nationwide Children’s Hospital, Center for Gene Therapy

2007–2010

  • Ruth L. Kirschstein Post-doctoral Fellow, National Institutes of Health, The Research Institute at Nationwide Children's Hospital, Mentor - Dr. Jerry Mendell

2005–2007

  • Post-doctoral Researcher, Center for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Mentor- Dr. Jerry Mendell

2001–2005

  • Graduate Research Associate, Department of Molecular Genetics, The Ohio State University

Publications

  • Chicoine, LG, Montgomery, CL, Bremer, WG, Shontz, KM, Griffin, DA, Heller, KN, Lewis, S, Malik, V, Shilling, CJ, Campbell, KJ, Preston, TJ, Coley, BD, Martin, PT, Walker, CM, Clark, KR, Sahenk, Z, Mendell, JR, and Rodino-Klapac, LR. 2013. Plasmapheresis eliminates the negative impact of AAV antibodies on therapeutic gene expression.  Molecular Therapy. Vol. 2, no. December: 338-347.
  • Chicoine, LG*, Rodino-Klapac, LR*, Xu, R, Shao, G, Bremer, WG, Camboni, M, Golden, B, Montgomery, CL, Shontz, KM, Heller, KN, Griffin, DA, Coley, BD, Walker, CM, Clark, KR, Sahenk, Z, Mendell, JR, and Martin, PT. 2013. Vascular delivery of rAAVrh74.MCK.GALGT2 in the rhesus macaque demonstrates widespread, sustained, functional muscle transgene expression, glycosylation of a dystroglycan, and upregulation of utrophin.  Molecular Therapy. Vol. NA, no. October: e10.1038/mt.2013.246.
  • Sahenk, Z, Galloway, G, Clark, KR, Malik, V, Rodino-Klapac, LR, Kaspar, BK, Chen, L, Braganza, C, Montgomery, C, and Mendell, JR. 2013. AAV1.NT-3 gene therapy for Charcot-Marie-Tooth neuropathy.  Molecular Therapy. Vol. NA, no. October: e: 10.1038/mt.2013.250.
  • Rodino-Klapac, LR. 2013. MicroRNA Based Treatment of Cardiomyopathy: Not all Dystrophies are Created Equal.  Journal of the American Heart Association. Vol. 2, no. 4. (August): ee000384.
  • Mendell, JR, Rodino-Klapac, LR, Sahenk, Z, Roush, K, Bird, L, Lowes, LP, Alfano, L, Gomez, AM, Lewis, S, Kota, J, Malik, V, Shontz, K, Walker, CM, Flanigan, KM, Kean, JR, Allen, HD, Shilling, CJ, Sazani, P, Saoud, JB, Laye, EM, Melia, KR. 2013. Eteplirsen Restores Dystrophin and Stabilizes Walking Ability in Patients with Duchenne’s Muscular Dystrophy.  Annals of Neurology. Vol. Epub, no. August: e10.1002/ana.23982.
  • Zarife Sahenk and Louise R. Rodino-Klapac. 2013. Dystrophinopathies. In In Neuromuscular Disorders in Clinical Practice. Edited by D. Katirji. New York: Springer Press.
  • Rodino-Klapac, LR, Janssen, PML, Shontz, KM, Canan, B, Montgomery, CL, Griffin, D, Heller, K, Schmelzer, L, Handy, Clark, KR, Sahenk, Z, Mendell, JR, and Kaspar, BK. 2013. Micro-dystrophin and Follistatin Co-Delivery Restores Muscle Function in.  Human Molecular Genetics. Vol. Epub ahead of print, no. July: ePMID:23863459.
  • Heller, KN, Montgomery, CL, Janssen, PML, Clark, KR, Mendell, JR, Rodino-Klapac, LR. 2013. AAV mediated overexpression of Human a7 Integrin leads to histological and functional improvement in dystrophic mice.  Molecular Therapy. Vol. 3, no. March: 520-525.
  • Rodino-Klapac,Louise,R; Mendell,Jerry,R; Sahenk,Zarife. 2013. Update on the treatment of Duchenne muscular dystrophy.  Current neurology and neuroscience reports. Vol. 13, no. 3. (January): e332..
  • Mendell,Jerry,R; Rodino-Klapac,Louise; Sahenk,Zarife; Malik,Vinod; Kaspar,Brian,K; Walker,Christopher,M; Clark,K,Reed. 2012. Gene therapy for muscular dystrophy: Lessons learned and path forward.  NEUROSCIENCE LETTERS. Vol. 527, no. 2. (October): 90-99.
  • Rosales-Quintero, X, Malik, V, Sneh, A, Chen, L, Lewis, S, Kota, J, Gastier-Foster, JM, Astbury, C, Pyatt, R, Reshmi, S, Rodino-Klapac, LR, Clark, KR, Mendell, JR, Sahenk, Z. 2012. Impaired regeneration in LGMD2A supported by increased Pax7 positive satellite cell content and muscle specific microRNA dysregulation.  Muscle and Nerve.. Vol. NA, no. September: e23669.
  • Grose,William,E; Clark,K,Reed; Griffin,Danielle; Malik,Vinod; Shontz,Kimberly,M; Montgomery,Chrystal,L; Lewis,Sarah; Brown,Robert,H; Janssen,Paul,ML; Mendell,Jerry,R; Rodino-Klapac,Louise,R. 2012. Homologous Recombination Mediates Functional Recovery of Dysferlin Deficiency following AAV5 Gene Transfer.  PLOS ONE. Vol. 7, no. 6. (June): ee39233.
  • Malik,Vinod; Rodino-Klapac,Louise,R; Mendell,Jerry,R. 2012. Emerging drugs for Duchenne muscular dystrophy.  EXPERT OPINION ON EMERGING DRUGS. Vol. 17, no. 2. (June): 261-277.
  • Beastrom N, Lu H, Macke A, Canan BD, Johnson EK, Penton CM, Kaspar BK, Rodino-Klapac LR, Zhou L, Janssen PM, Montanaro F. 2011. mdx(5cv) Mice Manifest More Severe Muscle Dysfunction and Diaphragm Force Deficits than Do mdx Mice.  Am J Pathol. Vol. N/A, no. September: eN/A.
  • Rodino-Klapac LR, Montgomery CL, Mendell JR, Chicoine LG. 2011. AAV-mediated gene therapy to the isolated limb in rhesus macaques.  Methods Mol Biol. Vol. 709, no. January: 287-98.
  • Louise R Rodino-Klapac, Chrystal L Montgomery, Jerry R Mendell, Louis G Chicoine. 2011. AAV Mediated Gene Therapy to the Isolated Limb in Rhesus Macaques. In Muscle Gene Therapy-Methods and Protocols.. Columbus: Humana Press.
  • Mendell, JR, Rodino-Klapac, LR, Rosales-Quintero, X, Kota, J, Coley, BD, Galloway, JM, Lewis, S, Malik, V, Shilling, CJ, Byrne, B, Conlon, T, Campbell, KJ, Bremer, WG, Taylor, LE, Flanigan, KM, Kota, J, Sahenk, Z, Walker, CM, Clark, KR. 2010. Sustained alpha-sarcoglycan gene expression after gene transfer in Limb-Girdle Muscular Dystrophy, Type 2D.  Annals of Neurology. Vol. 5, no. 68. (November): 629-38.
  • Malik, V, Rodino-Klapac, LR, Viollet, L, Mendell, JR. 2010. Aminoglycoside-induced mutation suppression (stop codon readthrough) as a therapeutic strategy for Duchenne muscular dystrophy.  Ther Adv Neurol Disord 3:379-89. Vol. 3, no. 6. (November): 379-89.
  • Mendell JR, Cambell CJ, Rodino-Klapac,LR, Sahenk Z, Shilling C, Lewis S, Bowles D, Gray,S, Li C, Galloway G, Malik V, Coley B, Clark KR, Li J, Xiao X,Samulski J, McPhee SW, Samulski RJ, Walker CM. 2010. Dystrophin Immunity Revealed by Gene Therapy in Duchenne Muscular.  New England Journal of Medicine. Vol. 15, no. 363. (October): 1429-1437.
  • Mendell,Jerry,R; Campbell,Katherine; Rodino-Klapac,Louise; Sahenk,Zarife; Shilling,Chris; Lewis,Sarah; Bowles,Dawn; Gray,Steven; Li,Chengwen; Galloway,Gloria; Malik,Vinod; Coley,Brian; Clark,K,Reed; Li,Juan; Xiao,Xiao; Samulski,Jade; McPhee,Scott,W; Samulski,R,Jude; Walker,Christopher,M. 2010. Brief Report: Dystrophin Immunity in Duchenne's Muscular Dystrophy.  NEW ENGLAND JOURNAL OF MEDICINE. Vol. 363, no. 15. (October): 1429-1437.
  • Mendell,Jerry,R; Campbell,Katherine; Rodino-Klapac,Louise; Sahenk,Zarife; Shilling,Chris; Lewis,Sarah; Bowles,Dawn; Gray,Steven; Li,Chengwen; Galloway,Gloria; Malik,Vinod; Coley,Brian; Clark,K,Reed; Li,Juan; Xiao,Xiao; Samulski,Jade; McPhee,Scott,W; Samulski,R,Jude; Walker,Christopher,M. 2010. Brief Report: Dystrophin Immunity in Duchenne's Muscular Dystrophy.  NEW ENGLAND JOURNAL OF MEDICINE. Vol. 363, no. 15. (October): 1429-1437.
  • Mendell JR, Rodino-Klapac LR, Malik V. 2010. Molecular Therapeutic Strategies Targeting Duchenne Muscular Dystrophy.  J Child Neurol. Vol. 9, no. 25. (September): 1145-1148.
  • Malik V, Rodino-Klapac LR, Viollet L, Wall C, King,W, Al-Dahhak R, Lewis S, Shilling CJ, Kota J, Serrano-Munuera C, Hayes J, Mahan JD, Campbell KJ, Banwell B, Dasouki M, Watts V, Sivakumar K, Bien-Willner R, Flanigan KM, Sahenk Z, Barohn RJ, Walker CM, Mendell JR. 2010. Gentamicin-Induced Readthrough of Stop Codons in Duchenne Muscular Dystrophy.  Annals of Neurology. Vol. 6, no. 67. (June): 771-780.
  • Rodino-Klapac LR, Montgomery CL, Bremer WG, Shontz KM, Malik V, Davis N, Sprinkle S, Campbell KJ, Sahenk Z, Clark KR, Waler CM, Mendell JR, Chicoine LG. 2010. Persistent expression of FLAG tagged micro-dystrophin in non-human primates with intramuscular and vascular delivery.  Molecular Therapy. Vol. 1, no. 18. (January): 109-117.
  • Mendell JR, Rodino-Klapac LR, Malik V. 2010. Strategies Targeting Duchenne Muscular Dystrophy.  J Child Neuro.
  • Malik V, Rodino-Klapac LR, Viollet L, Wall C, King W, Al-Dahhak R, Lewis S, Shilling CJ, Kota J, Serrano-Munuera C, Hayes J, Mahan JD, Campbell KJ, Banwell B, Dasouki M, Watts V, Sivakumar K, Bien-Willner R, Flanigan KM, Sahenk Z, Barohn RJ, Walker CM, Mendell JR. Gentamicin-induced readthrough of stop condons in duchenne muscular dystrophy. PubMed ID: 20517938
  • Rodino-Klapac LR, Montgomery CL, Bremer WG, Shontz KM, Malik V, Davis N, Sprinkle S, Campbell KJ, Sahenk Z, Clark KR, Walker CM, Mendell Jr, Chicoine LG. Persistent expression of FLAG-tagged micro dystrophin in nonhuman primates following intramuscular and vascular delivery.  Mol Ther. 2010 Jan .18(1): 109017 Epub 2009 Nov 10 PubMed ID: 19904237
  • Mendell Jr, Rodino-Klapac LR, Malik V. Molecular Therapeutic Strategies Targeting Muscular Dystrophy.  J Child Neurol. 2010 May 24 (Epub ahead of print) PubMed ID: 20498331
  • Kota J, Handy CR, Haidet AM, Montgomery CL, Eagle A, Rodino-Klapac LR, Tucker D, Shilling CJ, Therlfall WR, Walker CM, Weisbrode SE, Janssen PML, Clark KR, Sahenk Z, Mendell JR, Kaspar BK. 2009. Follistatin Gene Delivery Enhances Muscle Growth and Strength inNonHuman Primates.  Sci Transl Med. Vol. 6, no. 1. (November): 6-15.
  • Rodino-Klapac LR, Haidet AM, Kota J, Handy C, Kaspar BK, Mendell JR. 2009. Inhibition of Myostatin with Emphasis on Follistatin as a Therapy for Muscle Disease.  Muscle and Nerve. Vol. 3, no. 39. (March): 283-296.
  • Martin PT, Xu R, Rodino-Klapac LR, Oglesbay E, Camboni M, Montgomery CL, Shontz K, Chicoine LG, Clark KR, Sahenk Z, Mendell JR, Janssen PM. 2009. Overexpression of Galgt2 in Skeletal Muscle Prevents Injury Resulting from Eccentric Contractions in Both MDX and Wild Type Mice.  Am J Physiol Cell Physiol. Vol. 3, no. 296. (March): 476-488.
  • Hilario J, Rodino-Klapac LR, Wang C, Beattie CE. 2009. Semaphorin 5A Is A Bifunctional Axon Guidance Cue For Axial Motoneurons In Vivo.  Developmental Biology. Vol. 1, no. 326. (February): 190-200.
  • Martin PT, Xu R, Rodino-Klapac LR, Oglesbay E, Camboni M, Montgomery CL, Shontz K, Chicoine LG, Clark KR, Sahenk Z, Mendell Jr, Janssen PM. Overexpression of Galgt2 in skeletal muscle prevents injury resulting from eccentric contractions in both mdx and wild-type mice. Am J Physiol Cell Physioi. 2009 Mar;296(3):C476-88. Epub 2008 Dec 24 PubMed ID: 19109526
  • Rodino-Klapac LR, Haidet AM, Kota J, Handy C, Kaspar BK, Mendell JR. Inhibition of myostatin with emphasis on follistatin as a therapy for muscle disease.  Muscle Nerv. 2009 Mar;39(3):283-96. Review. PubMed ID: 19208403
  • Mendell JR, Rodino-Klapac LR, Rosales-Quintero X, Kota J, Coley BD, Galloway G, Craene JM, Lewis S, Malik V, Shilling C, Byrne BJ, Conlon T, Campbell KJ, Bremer WG, Violiet L, Walker CM, Sahenk Z, Clark KR.  Limb-girdle muscular dystrophy type 2D gene therapy restores alpha-sarcoglycan and associated proteins. Ann Nerol. 2009 Sept;666(3):290-7. PubMed ID: 1979725
  • Kota J. Handy CR, Haidet AM, Montgomery CL, Eagle A, Rodino-Klapac LR, Tucker D, Shilling CJ, Therifall WR, Walker CM, Weisbrode SE, Janssen PM, Clark KR, Sahenk Z, Mendell Jr, Kaspar BK.  Follistatin gene delivery enhances muscle growth and strength in nonhuman primates.  Sci Trans! Med. 2009 Nov 11:(6): 6ra15. PubMed ID: 20368179
  • Mendell JR, Rodino-Klapac LR, Rosales-Quintero X, KotaJ, Coley BD, Galloway G, Craenen JM, Lewis S, Malik V,Shilling C, Byrne BJ, Conlon T, Campbell KJ, Bremer WG, Viollet L, Walker CM, SahenkZ, Clark KR. 2009. Limb-girdle muscular dystrophy type 2D gene therapy restores alpha-sarcoglycan and associated proteins.  Ann Neurol. Vol. 66, no. January: 290-297.
  • Hilario JD, Rodino-Klapac LR, Vvang C, Beattie CE. Semaphorin 5A is a bifunctional axon guidance cue for axial motoneurons in vivo.  Dev Biiol. 2009 Feb 1;326(1): 190-200. Epub 2008 Nov 20 PubMed ID: 19059233
  • Rodino-Klapac LR, Lee JS, Mulligan RC, Clark KR, Mendell JR. 2008. Lack Of Toxicity of Alpha-Sarcoglycan Overexpression Supports Clinical Gene Transfer Trial in LGMD2D.  Neurology. Vol. 4, no. 71. (July): 240-247.
  • Rodino-Klapac LR, Lee JS, Mulligan RC, Clark KR, Mendell JR. Lack of toxicity of alpha-sarcoglycan overexpression supports clinical gene transfer trial in LGMD2D. Neurology. 2008 Jul 22;7(4):240-7. Epub 2008 Jun 4. PubMed ID: 18525034
  • Rodino-Klapac LR, Janssen PML, Montgomery CL, Coley BD, Chicoine LG, Clark KR, Mendell JR. 2007. A Translational Approach for Limb Vascular Delivery of the Micro-Dystrophin Gene Without High Volume or High Pressure for Treatment of Duchenne Muscular Dystrophy.  Journal of Translational Medicine. Vol. 45, no. 5. (September): e45.
  • Rodino-Klapac LR, Chicoine LG, Kaspar BK, Mendell JR. 2007. Gene Therapy for Duchenne Muscular Dystrophy: Expectations and Challenges.  Archives of Neurology. Vol. 9, no. 64. (September): 1236-1241.
  • Rodino-Klapac LR, Janssen PM, Comtgomery CL, Coley BD, Chicoine LG, Clark KR, Mendell JR. A translational approach for limb vascular delivery of the micro-dystrophin gene without high volume or high pressure for treatment of Duchenne muscular dystrophy. J Transl Med. 2007 Sept 24;5:45 PubMed ID: 18525034
  • Rodino-Klapac LR, Beattie CE. 2004. Zebrafish Topped is Required for Ventral Motor Axon Guidance.  Developmental Biology. Vol. 2, no. 273. (September): 308-320.
  • Rodino-Klapac LR, Chicoine LG, Kaspar BK, Mendell JR.Gene therapy for duchenne muscular dystrophy: expectations and challenges.  Arch Neurol. 2007 Sept;64(9);1236-41. Review. PubMed ID: 15328015
  • Rodino-Klapac LR, Beattie CE. Zebrafish topped is required for ventral motor axon guidance. Dev Biol.2004 Sept 15;273(2);308-20. PubMed ID: 15328015
  • Brian D Williams, Birutte Williams. Louise Rodino. 2000. Synthesis of the Sweetener Dulcin from the Analgesic Acetaminophen.  Journal of Chemical Education.
  • Rodino-Klapac, LR and Mendell, JR. Gene Therapy for Muscular Dystrophy. In 4th Edition of Gene and Cell Therapy: Therapeutic Mechanisms and Strategies. Taylor & Francis/CRC Press.
  • Al-Zaidy, S, Rodino-Klapac, LR, and Mendell, JR. Gene Therapy for Muscular Dystrophy: Moving the Field Forward.  J Child Neurol 2014.
  • Sahenk, Z and Rodino-Klapac, LR. Dystrophinopathies.  n Neuromuscular Disorders in Clinical Practice.
  • Chicoine, LG, Montgomery, CL, Bremer, WG, Shontz, KM, Griffin, DA, Heller, KN, Lewis, S, Malik, V, Shilling, CJ, Campbell, KJ, Preston, TJ, Coley, BD, Martin, PT, Walker, CM, Clark, KR, Sahenk, Z, Mendell, JR, and Rodino-Klapac, LR. Plasmapheresis eliminates the negative impact of AAV antibodies on therapeutic gene expression.  Molecular Therapy.
  • Sondergaard, P*, Pozsgai, ER*, Grose, WE, Griffin, DA, and Rodino-Klapac, LR. AAV Mediated Dysferlin Gene Transfer Restores Muscle Membrane Repair Capacity.  JoVE. 2014.
Nationwide Children's Hospital
700 Children's Drive Columbus, Ohio 43205 614.722.2000