1986 Senior Staff Fellow, Human Genetics Branch National Institute of Child Health and Human Developmental Bethesda, MD

J. Muenzer, M.D., Ph.D.

CURRICULUM VITAE

1) Education:

1985 - 1986 Senior Staff Fellow, Human Genetics Branch National Institute of Child Health and Human Developmental Bethesda, MD

1982 - 1985 Medical Staff Fellow, Human Genetics Branch National Institute of Child Health and Human Developmental, Bethesda, MD

1980 - 1982 Resident, Department of Pediatrics, University of Wisconsin Hospital, Madison, WI

1979 - 1980 Intern, Department of Pediatrics, University of Wisconsin Hospital, Madison, WI

1979 M.D., Case Western Reserve University, Cleveland, OH

1977 - 1978 Research Fellow, Cleveland V.A. Hospital, Cleveland, OH (Total 4 months)

1976 Ph.D., Biochemistry, Case Western Reserve University, Cleveland, OH

1970 B.A., Chemistry, Kalamazoo College, Kalamazoo, MI

2) Professional Experience - Employment History:

2009-present Research Professor, Department of Genetics University of North Carolina at Chapel Hill

2007-present Professor, Department of Pediatrics University of North Carolina at Chapel Hill

2001-2009 Research Associate Professor, Department of Genetics University of North Carolina at Chapel Hill

1996 – 2001 Research Scientist, UNC Neuroscience Center University of North Carolina at Chapel Hill

1994 – 1996 Research Scientist, Brain Development Research Center University of North Carolina at Chapel Hill

1993 - 2007 Associate Professor, Department of Pediatrics University of North Carolina at Chapel Hill

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1986 - 1993 Assistant Professor, Department of Pediatrics University of Michigan School of Medicine

1970 - 1971 Chemist, National Institute of Arthritis, Metabolic and Digestive Diseases Bethesda, MD

3) Honors:

1. Achievements in Patient Care Award , National MPS Society, May 2, 2014.

2. Listed in “Best Doctors in America” 2011 to 2016.

3. James Emonson Faculty (Teaching) Honor, North Carolina Children’s Hospital, 2009.

4) Bibliography:

Chapters in Books:

1. Kliegman, RM. And Muenzer, J. Mucopolysaccharidoses. Nelson Textbook of Pediatrics, 17th edition, Chapter 77: 482-486, 2004. 2. Neufeld, E.F. and Muenzer, J. The Mucopolysaccharidosis. Metabolic and Molecular Basis of Inherited Disease, 8th edition, Chapter # 136: 3421-52, 2001. 3. Muenzer, J. Mucopolysaccharidoses. Nelson Textbook of Pediatrics, 16th edition, Chapter 85: 420-423, 2000. 4. Neufeld, E.F. and Muenzer, J. The Mucopolysaccharidosis. Metabolic Basis of Inherited Disease, 7th edition, Chapter 78: 2465-94, 1995. 5. Muenzer, J., Catastrophic metabolic disease in the newborn. In Neonatal Emergency, Ed., Donn, S.M. and Faix, R.G., Futura Publishing, NY Chapter 28: 501-511, 1991 6. Neufeld, E.F. and Muenzer, J. The Mucopolysaccharidosis. Metabolic Basis of Inherited Disease, 6th edition, Chapter 61: 1565-1587, 1989. 7. Muenzer, J. Mucopolysaccharidosis. Advances in Pediatrics Vol. 33: 269-302, 1986. 8. Yergey, A.L., Vieira, N.E., Covell, D., and Muenzer, J. Studies of human calcium kinetics with stable isotopic kinetics, In: Synthesis and Application of Isotopically Labeled Compounds, 1985, R.R. Mucino (Ed.) Elsevier Science Publishers, Amsterdam p. 343-348, 1986.

Publications in Scientific Journals (Peer Reviewed):

1. Couser NL, Marchuk DS, Smith LD, Arreola A, Kaiser-Rogers KA, Muenzer J, Pandya A, Gucsavas-Calikoglu M, Powell CM. Co-occurring Down syndrome and SUCLA2-related mitochondrial depletion syndrome. Am J Med Genet A. 2017 Jul 27. PMID: 28749033

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2. van der Lee JH, Morton J, Adams HR, Clarke L, Ebbink BJ, Escolar ML, Giugliani R, Harmatz P, Hogan M, Jones S, Kearney S, Muenzer J, Rust S, Semrud-Clikeman M, Wijburg FA, Yu ZF, Janzen D, Shapiro E. Cognitive endpoints for therapy development for neuronopathic mucopolysaccharidoses: Results of a consensus procedure. Mol Genet Metab. 2017 Jun;121(2):70-79. PMID: 28501294 3. Muenzer J, Jones SA, Tylki-Szymańska A, Harmatz P, Mendelsohn NJ, Guffon N, Giugliani R, Burton BK, Scarpa M, Beck M, Jangelind Y, Hernberg-Stahl E, Larsen MP, Pulles T, Whiteman DAH. Ten years of the Hunter Outcome Survey (HOS): insights, achievements, and lessons learned from a global patient registry. Orphanet J Rare Dis. 2017 May 2;12(1):82. PMID: 28464912 4. Clarke LA, Atherton AM, Burton BK, Day-Salvatore DL, Kaplan P, Leslie ND, Scott CR, Stockton DW, Thomas JA, Muenzer J. Mucopolysaccharidosis Type I Newborn Screening: Best Practices for Diagnosis and Management. J Pediatr. 2017 Mar;182:363-370. 5. Wooten WI 3rd, Muhlebach MS, Muenzer J, Loughlin CE, Vaughn BV. Progression of Polysomnographic Abnormalities in Mucolipidosis II (I-Cell Disease). J Clin Sleep Med. 2016 Dec 15;12(12):1695-1696. 6. Pupavac M, Watkins D, Petrella F, Fahiminiya S, Janer A, Cheung W, Gingras AC, Pastinen T, Muenzer J, Majewski J, Shoubridge EA, Rosenblatt DS. Inborn Error of Cobalamin Metabolism Associated with the Intracellular Accumulation of Transcobalamin-Bound Cobalamin and Mutations in ZNF143, Which Codes for a Transcriptional Activator. Hum Mutat. 2016 Sep;37(9):976-82.PMID: 27349184. 7. Couser NL, McClure J, Evans MW, Haines NR, Burden SK, Muenzer J. Homocysteinemia due to MTHFR deficiency in a young adult presenting with bilateral lens subluxations. Ophthalmic Genet. 2016 Apr 4:1-4. PMID: 27046515. 8. Fan Z, Kocis K, Valley R, Howard J Jr, Chopra M, Chen Y, An H, Lin W, Muenzer J, Powers W. High-pressure Transvenous Perfusion of the Upper Extremity in Human Muscular Dystrophy: A Safety Study with 0.9% Saline. Hum Gene Ther. 2015 Sep;26(9):614-21. doi: 10.1089/hum.2015.023. Epub 2015 Jul 30. PMID: 25953425. 9. Muenzer J, Hendriksz CJ, Fan Z, Vijayaraghavan S, Perry V, Santra S, Solanki GA, Mascelli MA, Pan L, Wang N, Sciarappa K, Barbier AJ. A phase I/II study of intrathecal idursulfase-IT in children with severe mucopolysaccharidosis II. Genet Med. 2016 Jan;18(1):73-81. doi: 10.1038/gim.2015.36. Epub 2015 Apr 2. 10. Wiklund I, Raluy-Callado M, Chen WH, Muenzer J, Fang J, Whiteman D. The Hunter Syndrome-Functional Outcomes for Clinical Understanding Scale (HS-FOCUS) Questionnaire: item reduction and further validation. Qual Life Res. 2014 Nov; 23(9):2457- 62. 11. Beck M, Arn P, Giugliani R, Muenzer J, Okuyama T, Taylor J, Fallet S. The natural history of MPS I: global perspectives from the MPS I Registry. Genet Med. 2014 Oct;16(10):759-65. 12. Lampe C, Atherton A, Burton BK, Descartes M, Giugliani R, Horovitz DD, Kyosen SO, Magalhães TS, Martins AM, Mendelsohn NJ, Muenzer J, Smith LD. Enzyme Replacement Therapy in Mucopolysaccharidosis II Patients Under 1 Year of Age. JIMD Rep. 2014;14:99- 113. 13. Muenzer J. Early initiation of enzyme replacement therapy for the mucopolysaccharidoses. Mol Genet Metab. 2014 Feb;111(2):63-72.

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14. Chen Y, Fan Z, Ji S, Muenzer J, An H, Lin W. Patient-specific biomechanical modeling of ventricular enlargement in hydrocephalus from longitudinal magnetic resonance imaging. Med Image Comput Comput Assist Interv. 2013;16(Pt 3):291-8. 15. Wooten WI 3rd, Muenzer J, Vaughn BV, Muhlebach MS. Relationship of sleep to pulmonary function in mucopolysaccharidosis II. J Pediatr. 2013 Jun;162(6):1210-5. 16. Muhlebach MS, Shaffer CB, Georges L, Abode K, Muenzer J. Bronchoscopy and airway management in patients with mucopolysaccharidoses (MPS). Pediatr Pulmonol. 2013 Jun;48(6):601-7. 17. Muenzer J, Bodamer O, Burton B, Clarke L, Frenking GS, Giugliani R, Jones S, Rojas MV, Scarpa M, Beck M, Harmatz P. The role of enzyme replacement therapy in severe Hunter syndrome-an expert panel consensus. Eur J Pediatr. 2012 Jan;171(1):181-8. Epub 2011 Oct 29. 18. Muenzer J. Overview of the mucopolysaccharidoses. Rheumatology (Oxford). 2011 Dec; 50 Suppl 5:v4-v12. 19. Fan Z, Kocis K, Valley R, Howard JF, Chopra M, An H, Lin W, Muenzer J, Powers W. Safety and Feasibility of High-pressure Transvenous Limb Perfusion With 0.9% Saline in Human Muscular Dystrophy. Mol Ther. 2012 Feb;20(2):456-61. doi: 10.1038/mt.2011.137. Epub 2011 Jul 19. 20. Muhlebach MS, Wooten W, Muenzer J. Respiratory manifestations in mucopolysaccharidoses. Paediatr Respir Rev. 2011 Jun;12(2):133-8. Epub 2010 Nov 26. 21. Bien Lai, Joseph Muenzer and Michael W. Roberts. Idiopathic Gingival Hyperplasia: A Case Report with a 17-Year Followup. Case Reports in DentistryVolume 2011 (2011), Article ID 986237, 5 pagesdoi:10.1155/2011/986237. 22. Muenzer J, Beck M, Giugliani R, Suzuki Y, Tylki-Szymanska A, Valayannopoulos V, Vellodi A, Wraith JE. Idursulfase treatment of Hunter syndrome in children younger than 6 years: results from the Hunter Outcome Survey. Genet Med. 2011 Feb;13(2):102-9. 23. Muenzer J, Beck M, Eng CM, Giugliani R, Harmatz P, Martin R, Ramaswami U, Vellodi A, Wraith JE, Cleary M, Gucsavas-Calikoglu M, Puga AC, Shinawi M, Ulbrich B, Vijayaraghavan S, Wendt S, Conway AM, Rossi A, Whiteman DA, Kimura A. Long-term, open-labeled extension study of idursulfase in the treatment of Hunter syndrome. Genet Med. 2011 Feb;13(2):95-101. 24. Fu H, DiRosario J, Kang L, Muenzer J, McCarty DM. Restoration of central nervous system alpha-N-acetylglucosaminidase activity and therapeutic benefits in mucopolysaccharidosis IIIB mice by a single intracisternal recombinant adeno-associated viral type 2 vector delivery. J Gene Med. 2010 Jul;12(7):624-33. 25. Fan Z, Styner M, Muenzer J, Poe M, Escolar M. Correlation of Automated Volumetric Analysis of Brain MR Imaging with Cognitive Impairment in a Natural History Study of Mucopolysaccharidosis II. Am J Neuroradiol. 2010 Aug;31(7):1319-23. Epub 2010 Mar 4 26. Beck M, Muenzer J, Scarpa M. Evaluation of disease severity in mucopolysaccharidoses. J Pediatr Rehabil Med. 2010;3(1):39-46. 27. Muenzer J, Beck M, Eng CM, Escolar ML, Giugliani R, Guffon NH, Harmatz P, Kamin W, Kampmann C, Koseoglu ST, Link B, Martin RA, Molter DW, Muñoz Rojas MV, Ogilvie JW, Parini R, Ramaswami U, Scarpa M, Schwartz IV, Wood RE, Wraith E. Multidisciplinary management of Hunter syndrome. Pediatrics. 2009 Dec;124(6):e1228-39.

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28. McCarty DM, DiRosario J, Gulaid K, Muenzer J, Fu H. Mannitol-facilitated CNS entry of rAAV2 vector significantly delayed the neurological disease progression in MPS IIIB mice. Gene Ther. 2009 Nov;16(11):1340-52. 29. Surekha P and Muenzer J. The Diagnosis and Management of a Female With Mild Citrullinemia and Undetectable Argininosuccinate Synthetase Activity in Fibroblasts. Topics in Clinical Nutrition, 24:366:373. 30. Clarke LA, Wraith JE, Beck M, Kolodny EH, Pastores GM, Muenzer J, Rapoport DM, Berger KI, Sidman M, Kakkis ED, Cox GF. Long-term efficacy and safety of laronidase in the treatment of mucopolysaccharidosis I. Pediatrics. 2009 Jan;123(1):229-40. 31. Muenzer J, Wraith JE, Clarke LA; International Consensus Panel on Management and Treatment of Mucopolysaccharidosis I. Mucopolysaccharidosis I: management and treatment guidelines. Pediatrics. 2009 Jan;123(1):19-29. 32. Wraith JE, Beck M, Giugliani R, Clarke J, Martin R, Muenzer J; HOS Investigators. Initial report from the Hunter Outcome Survey. Genet Med. 2008;10(7):508-16. 33. Muenzer J, Martins AM. Hunter syndrome: to treat or not to treat. Acta Paediatr Suppl. 2008; 97(457):55-6 34. Martin R, Beck M, Eng C, Giugliani R, Harmatz P, Muñoz V, Muenzer J. Recognition and diagnosis of mucopolysaccharidosis II (Hunter syndrome). Pediatrics. 2008 Feb;121(2):377- 86. 35. Whitley CB, Barranger JA, Eng CM, Davidson B, Grabowski GA, Muenzer J, Pastores GM, Patel SK, Shapiro EG, Steiner RD, Walkley SU, Wedehase BA, Wilcox WR. Lysosomal Disease Network's "WORLD Symposium 2008". Mol Genet Metab. 2008 Feb;93(2):S3-5. 36. Garcia AR, Pan J, Lamsa JC, Muenzer J. The characterization of a murine model of mucopolysaccharidosis II (Hunter syndrome). Inherit Metab Dis. 2007 30(6):924-34. 37. Fu H, Kang L, Jennings JS, Moy SS, Perez A, Dirosario J, McCarty DM, Muenzer J. Significantly increased lifespan and improved behavioral performances by rAAV gene delivery in adult mucopolysaccharidosis IIIB mice. Gene Ther. 2007 Jul;14(14):1065-77 38. Garcia AR, DaCosta JM, Pan J, Muenzer J, Lamsa JC. Preclinical dose ranging studies for enzyme replacement therapy with idursulfase in a knock-out mouse model of MPS II. Mol Genet Metab. 2007 Jun;91(2):183-90. 39. Pastores GM, Arn P, Beck M, Clarke JT, Guffon N, Kaplan P, Muenzer J, Norato DY, Shapiro E, Thomas J, Viskochil D, Wraith JE. The MPS I registry: design, methodology, and early findings of a global disease registry for monitoring patients with Mucopolysaccharidosis Type I. Mol Genet Metab. 2007 May;91(1):37-47. 40. Muenzer J, Gucsavas-Calikoglu M, McCandless SE, Schuetz TJ, Kimura A. A phase I/II clinical trial of enzyme replacement therapy in mucopolysaccharidosis II (Hunter syndrome). Mol Genet Metab. 2007 Mar;90(3):329-37. 41. Monte S. Willis, Alice A. Basinger, Zheng Fan, Surekha Pendyal, Joseph Muenzer, Catherine Hammett-Stabler. Hepatosplenomegaly in an 8 Month-Old Child. Laboratory Medicine. 2006 Nov, 37:665-695. 42. Muenzer J, Wraith JE, Beck M, Giugliani R, Harmatz P, Eng CM, Vellodi A, Martin R, Ramaswami U, Gucsavas-Calikoglu M, Vijayaraghavan S, Wendt S, Puga A, Ulbrich B, Shinawi M, Cleary M, Piper D, Conway AM, Kimura A. A phase II/III clinical study of

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enzyme replacement therapy with idursulfase in mucopolysaccharidosis II (Hunter syndrome). Genet Med. 2006 Aug; 8 (8):465-473. 43. Frazier DM, Millington DS, McCandless SE, Koeber DD, Weavil SD, Chaing SH, Muenzer J. The tandem mass spectrometry newborn screening experience in North Carolina: 1997-2005. J Inherit Metab Dis. 2006 Feb; 29:76-85. 44. Basinger AA, Booker JK, Frazier DM, Koeberl DD, Sullivan JA, Muenzer J. Glutaric acidemia type 1 in patients of Lumbee heritage from North Carolina. Mol Genet Metab. 2006 May;88:90-2. 45. Friso A, Tomanin R, Alba S, Gasparotto N, Puicher EP, Fusco M, Hortelano G, Muenzer J, Marin O, Zacchello F, Scarpa M. Reduction of GAG storage in MPS II mouse model following implantation of encapsulated recombinant myoblasts. J Gene Med. 2005 Nov; 7:1482-91. 46. Matheus MG, Castillo M, Smith JK, Armao D, Towle D, Muenzer J. Brain MRI findings in patients with mucopolysaccharidosis types I and II and mild clinical presentation. Neuroradiology. 2004 Aug; 46(8):666-72. 47. Muenzer J, Fisher A. Advances in the treatment of mucopolysaccharidosis type I. N Engl J Med. 2004 May 6; 350(19):1932-4. 48. Wraith JE, Clarke LA, Beck M, Kolodny EH, Pastores GM, Muenzer J, Rapoport DM, Berger KI, Swiedler SJ, Kakkis ED, Braakman T, Chadbourne E, Walton-Bowen K, Cox GF. Enzyme replacement therapy for mucopolysaccharidosis I: a randomized, double-blinded, placebo-controlled, multinational study of recombinant human alpha-L-iduronidase (laronidase). J Pediatr. 2004 May;144(5):581-8. 49. Muenzer, J. The mucopolysaccharidoses: a heterogeneous group of disorders with variable pediatric presentations. J Pediatr. 2004 May;144(5 Suppl):S27-34. 50. Fu H, Muenzer J, Samulski RJ, Breese G, Sifford J, Zeng X, McCarty DM. Self- complementary adeno-associated virus serotype 2 vector: global distribution and broad dispersion of AAV-mediated transgene expression in mouse brain. Mol Ther. 2003 Dec;8(6):911-7. 51. Koeberl DD, Millington DS, Smith WE, Weavil SD, Muenzer J, McCandless SE, Kishnani PS, McDonald MT, Chaing S, Boney A, Moore E, Frazier DM. Evaluation of 3- methylcrotonyl-CoA carboxylase deficiency detected by tandem mass spectrometry newborn screening. J Inherit Metab Dis. 2003;26(1):25-35. 52. Muenzer J, Lamsa JC, Garcia A, Dacosta J, Garcia J, Treco DA. Enzyme replacement therapy in mucopolysaccharidosis type II (Hunter syndrome): a preliminary report. Acta Paediatr Suppl. 2002; 91(439):98-9. 53. Mareska MC, Adams KK, Muenzer J, Braun TG, Howard JF: Late onset presentation of glutaric acidemia type II with myopathy. Journal of Clinical Neuromuscular Disease 2003, 4:124-8. 54. Fu, H, Samulski, RJ, McCown, TJ, Picornel, YJ, Fletcher, D and Muenzer, J. Neurological correction of lysosomal storage in a mucopolysaccharidosis IIIB mouse model by adeno- associated virus-mediated gene delivery. Molecular Therapy 2002, 5:42-9. 55. Kakkis ED. Muenzer J. Tiller GE. Waber L. Belmont J. Passage M. Izykowski B. Phillips J. Doroshow R. Walot I. Hoft R. Neufeld EF. Enzyme-replacement therapy in mucopolysaccharidosis I. New England Journal of Medicine. 344(3):182-8, 2001.

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56. Andresen BS. Dobrowolski SF. O'Reilly L. Muenzer J. McCandless SE. Frazier DM. Udvari S. Bross P. Knudsen I. Banas R. Chace DH. Engel P. Naylor EW. Gregersen N. Medium- chain acyl-CoA dehydrogenase (MCAD) mutations identified by MS/MS-based prospective screening of newborns differ from those observed in patients with clinical symptoms: identification and characterization of a new, prevalent mutation that results in mild MCAD deficiency. American Journal of Human Genetics. 68(6):1408-18, 2001. 57. Weston, BW, Lin, J, Muenzer, J, et al. Glucose-6-phosphate mutation G188R confers an atypical glycogen storage disease type 1b phenotype. Pediatric Research 2000, 48: 329-34. 58. Reitnauer, PJ, Chaing, S and Muenzer, J. Why do critically ill newborns not get mandated screening? North Carolina Medical Journal 1999, 60: 256-58. 59. Van Hove, JL, Kishnani, P, Muenzer, et al. Benzoate therapy and carnitine deficiency in non- ketotic hypergycinemia. Am. J. Medical Genetics 1995, 59:444-53. 60. Marowitz, AJ, Chen, YT, Muenzer, J, Delbunono, EA, and Lucey, MR. A man with Type III glycogenosis associated with cirrhosis and portal hypertension. Gastroenterology 1993, 105: 1882-5. 61. Muenzer, J., Beekman, R.H., Profera, L.M., and Bove, E.L. Severe mitral insufficiency in mucopolysaccharidosis type III-B (Sanfilippo syndrome). Pediatr Cardiol 14:130-132, 1993. 62. Muenzer, J., Neufeld, E.F., Contanopolus, G.G. et al. Attempted enzyme replacement using human amnion membrane implantations in mucopolysaccharidosis. J Inher. Metab. Dis. 1992, 15:25-37. 63. Abrams, S.A., Sidbury, J.B., Muenzer, J., Esteban, N.V., Vieira, N.E., and Yergey, A.L. Stable isotopic measurement of endogenous fecal calcium excretion in children. J Pediatr Gastroenterol Nutr 1991, 12:469-473. 64. Robertson, PL., Buchanan, DN., and Muenzer, J. 5-Oxoprolinuria in an adolescent with chronic metabolic acidosis, mental retardation, and psychosis. J. Pediatr 1991, 118:92-5. 65. Buchanan, D.N., Muenzer, J., and Thoene, J.G. Positive ion thermospray liquid chromatography/mass spectrometry: Detection of organic acidurias. J Chromatogr/Biomedical Applications 1990, 534:1-11. 66. Bliziotes, M., Yergey, A., Nanes, M., Muenzer, J., Begley, M., Vieira, N., Kher, K., Brandi, M.L., and Marx, S. Absent intestinal response to 1,25 dihydroxyvitamin Documentation in vivo and in vitro and effective therapy with high dose intravenous calcium infusions. J Clin Endocrinol Metab 1988, 66:294-300. 67. Caruso, R.C., Kaiser-Kupfer, M.I., Muenzer, J., Ludwig, I.H., Zasloff, M.A., and Mercer, P.A. Electroretinographic Findings in the Mucopolysaccharidosis. Ophthalmology 1986, 93:1612- 6. 68. Muenzer, J., Bildstein, C., Gleason, M., and Carlson, D.M. Properties of proline-rich proteins from parotid gland of isoproterenol-treated rats. J. Biol. Chem. 1979; 254: 5629-34. 69. Muenzer, J., Bildstein, C., Gleason, M., and Carlson, D.M. Purification of proline-rich proteins from parotid gland of isoproterenol-treated rats. J. Biol. Chem. 1979; 254: 5623-8. 70. Muenzer, J., Weinbach, E.C., and Wolfe, S.M. Oxygen consumption of human blood platelets. II. Effects of inhibitors. B.B.A. 1975; 376: 243-8. 71. Muenzer, J., Weinbach, E.C., and Wolfe, S.M. Oxygen consumption of human blood platelets. I. Effects of Thrombin. B.B.A. 1975; 376: 237-42.

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72. Roth, J., Prout, T.E., Goldfine, I.D., Wolfe, S.M., Muenzer, J., Grauer, L.E., and Marcus, M.L. Sulfonylureas: Effects in Vivo and in Vitro. Ann. Intern. Med. 1971; 75: 607-21. 73. Gordon, R.S., Thompson, R.H., Muenzer, J., and Thrasher, D. Sweat lactate in man is derived from blood glucose. J. Appl.Physiol. 1971; 31: 713-6.

5) Teaching record:

University of North Carolina at Chapel Hill (1993 to present):

Attending on Clinical Service/activities

Pediatric Biochemical Genetics and Metabolism consultation service: three to twelve months per year General Attending on Pediatric in-patient service: one month each year (1994 to 2002) Pediatric Biochemical Genetics and Metabolism out-patient clinic: one to two day each week

Clinical Teaching

Teaching of residents and/or medical students on the Pediatrics Genetics and Metabolism elective Pediatric Genetics and Metabolism Teaching Conference, weekly, throughout the year Presentations at Pediatric Grand Rounds and at other departmental seminars

Lecture given since July 2013

1. Invited speaker (two talks), Latin American Course on Lysosomal Storage Diseases, Cartagena , Columbia, Oct 30-Nov 4, 2016. 2. Invited speaker, “Gene Therapy for the Neurologic Manifestations of Mucopolysaccharidoses”, Fall 2016 North Carolina Medical Genetics Meeting and Educational Conference, Chapel Hill, NC, October 28, 2016. 3. Invited speaker (two talks), “ Overview MPS Disorder – Current Landscape” and “Future Therapies”, Mucopolysaccharidosis Master Class for Genetic Counselors and Nurse Pactitioners, UCSF Benioff Children’s Hospital Oakland, Sept 29 – Oct 1, 2016. 4. Invited speaker, “Overview of Mucopolysaccharidoses (MPS) and New Treatment Strategies” Lysosomal Storage Diseases: The Trek from Patients to Genes and Back conference, American University of Beirut Medical Center, Beirut, Lebanon, September 3, 2016. 5. Invited speaker (two talks), 30th Annual National MPS Society Family conference, Columbus, Ohio, Aug 4-6, 2016. 6. Invited speaker, “Gene Therapy for Neurologic Manifestation of MPS”, 14th International Symposium on MPS and Related Diseases, Bonn, Germany, July 14-17, 2016. 7. Co-chair and keynote speaker, MPS II Advanced Masterclass, Barcelona, Spain, May 13- 14, 2016. 8. Invited speaker (two talks), MPS II Traditional Masterclass, Barcelona, Spain, May 12-13, 2016. 9. Invited speaker, “Learning from the Brain (Intrathecal) Delivery Options for ERT”, The Brain in MPS” Today and Tomorrow meeting, Stockholm, Sweden, April 28-29, 2015. 10. Invited speaker, “Benefits of Early MPS II Diagnosis and Treatment: Efficacy of Long- Term ERT”, MPS II Shire-SLEIPMN Symposium, Santiago, Chile, Nov 19, 2015.

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11. Invited speaker, “Overview of MPS and New Treatment Strategies”, Shire, Zug, Switerland, Oct 15, 2015. 12. Invited speaker, “New Strategies for the Treatment of the CNS Disease in MPS”, 3rd MPS Forum, Tokyo, Japan, August 8, 2015. 13. Invited speaker (two talks) at the 6th Congreso Latinoamericano de Enfermedades Lisosomales - COLATEL (6th Latin American Congress of Lysosomal Storage Diseases) June 2015, Sao Paulo, Brazil. 14. Invited keynote speaker, MPS II Advanced Masterclass, Berlin Germany, May 2015. Sponsored by Shire HGT. 15. Co-chaired and invited speaker (two talks), MPS II Traditional Masterclass, Berlin Germany, May 2015. Sponsored by Shire HGT. 16. Invited speaker (four talks), RARE Summit, an educational symposium on lysosomal storage disorders for Mexican physicians, Cancun, Mexico, April 2015. 17. Second year UNC Medical School Lecture, “Treatment of Metabolic Disorders”, April, 2015. 18. Second year UNC Medical School Lecture, “Newborn Screening”, April, 2015. 19. Invited speaker, 9th Brains for Brain Plenary Workshop, Frankfurt, Germany, Feb 5-7, 2015. 20. Invited speaker, Pediatric Grand Rounds, Nemours Children’s Hospital, Orlando, FL, Nov 18, 2014. 21. Faculty member and speaker for the IV Latin American Course on Lysosomal Storage Diseases, Gramado, RS, Brazil, Nov 2-7, 2014. 22. Invited speaker for two talks, 13th International Symposium on Mucopolysaccharidoses and Related Diseases, Bahia, Brazil Aug 13-17, 2014. 23. UNC Neurology Grand Rounds, “New Strategies for the Treatment of the CNS Disease in Mucopolysaccharidoses (MPS)”, June 19, 2014. 24. Invited Speaker, “Abnormal Newborn Screen Results: What Do They Mean And What To Do Next?, June 6, 2014, Annual McArtor Symposium, Wilmington, NC. 25. Invited Speaker, “Status of Current Treatment and New Strategies for the Treatment of the CNS Disease in Mucopolysaccharidoses (MPS), May 17, 2014, Seattle, Washington. 26. Co-chaired and invited speaker, MPS II Advanced Masterclass, Prague, Czech Republic, April 28-30, 2014. Sponsored by Shire HGT. 27. Co-chaired and invited speaker, MPS II Traditional Masterclass, Prague, Czech Republic, April 28-30, 2014. Sponsored by Shire HGT. 28. Second year UNC Medical School Lecture, “Treatment of Metabolic Disorders”, April, 2014. 29. Second year UNC Medical School Lecture, “Newborn Screening”, April, 2014. 30. Invited Speaker, “Overview of Mucopolysaccharidosis (MPS I) and Treatment Options/Limitations”, March 17, 2014, PTC Therapeutics, South Plainfield, New Jersey. 31. Invited Speaker, “Treatment of the CNS Disease in MPS”, Nov 5th, 2013. Seoul, South Korea, 3rd Conference for the Korea Society of Inherited Metabolic Disease.

6) Grants:

2016- SHP-610-201. An Open-Label Extension of Study HGT-SAN-093 Evaluating the Safety and Efficacy of HGT-1410 (Recombinant Human Heparan N Sulfatase) Administration via an Intrathecal Drug Delivery Device in Pediatric Patients with Mucopolysaccharidosis Type IIIA Disease. Sponsor: Shire. J. Muenzer, P.I. $401.954.

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2016-2017 Newborn Screening Pilot Studies: MPS I Pilot Study. Sponsor: NIH/RTI Subcontract. J. Muenzer, co-P.I. $34,462

2015- SHP-609-302. An Open Label Extension of Study HGT-HIT-094 Evaluating Long Term Safety and Clinical Outcomes of Intrathecal Idursulfase Administered in Conjunction with Elaprase® in Patients with Hunter Syndrome and Cognitive Impairment. Sponsor: Shire. J. Muenzer, P.I. $2,043,638

2015-2016 HGT-SAN-093. A Randomized, Controlled, Open-label, Multicenter, Phase IIb Safety and Efficacy Study of HGT-1410 (Recombinant Human Heparan N Sulfatase) Administration via an Intrathecal Drug Delivery Device in Pediatric Patients with Early Stage Mucopolysaccharidosis Type III A Disease. Sponsor: Shire. J. Muenzer, P.I. $269,077.

2014- HGT-HIT-094. A Controlled, Randomized, Two-arm, Open-label, Assessor-blinded Multicenter Study of Intrathecal Idursulfase-IT Administered in Conjunction with Elaprase® in Pediatric Patients with Hunter Syndrome and Early Cognitive Impairment. Sponsor: Shire. J. Muenzer, P.I. $932,632

2013-2016 HGT-HIT-090. A perspective longitudinal observational study to evaluate neurodevelopmental status impatience with pediatric patients with Hunter syndrome. Sponsor: Shire. J. Muenzer, P.I. $127,000.

2012-2014 HGT-HIT-072. A cerebral spinal fluid collection study in the pediatric and adult patients with Hunter syndrome. Sponsor: Shire. J. Muenzer, P.I. $3,995

2010- PKU Demographics, Outcome and Safety Registry. Sponsor: BioMarin. J. Muenzer, P.I. $94,135

2009- HGT-HIT-046. An Open-Label Extension of Study HGT-HIT-045 Evaluating Long-Term Safety and Clinical Outcomes of Intrathecal Idursulfase-IT, Administered in Conjunction with Intravenous Elaprase in Pediatric Patients with Hunter Syndrome and Early Cognitive Impairment. Sponsor: Shire. J. Muenzer, P.I. $2,141,356.

2006- Hunter Outcome Survey. A Global, multicenter observational survey of patients with Hunter syndrome. Sponsor: Shire. J. Muenzer, P.I $69,000

2012-2014 PKU 016. A double-blind placebo controlled randomized study to evaluate the safety and therapeutic effects of saprppterin dihydrochloride on neuropsychiatric symptoms in subjects with phenylketonuria. Sponsor: BioMarin. J. Muenzer, P.I. $31,640

2009-2014 HGT-HIT-045. A Phase I/II Randomized Safety and Ascending Dose Ranging Study of Idursulfase (Intrathecal) Administration via an Intrathecal Drug Delivery Device in Pediatric Patients with Hunter Syndrome Who Demonstrate Evidence of Central Nervous System

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Involvement and Who Are Receiving Treatment with Elaprase. Sponsor: Shire. J. Muenzer, P.I. $1,204,197.

2009-2012 HGT-HIT-050. A Screening Study to Identify Pediatric Patients with Hunter Syndrome Who Demonstrate Evidence of Central Nervous System Involvement and Who are Currently Receiving Treatment with Elaprase. Sponsor: Shire. J. Muenzer, P.I. $83,280.

2009-2011 MPS II AAV Gene Therapy, funded by the Canada MPS Society. J. Muenzer, P.I., $100,00 CAD.

2006-2008 AAV Gene Therapy for Mucopolysaccharidosis II, funded by the National MPS Society, J. Muenzer, P.I., $120,000.

2005-2007 An Open-Label Extension Study TKT024 Evaluating Long-Term Safety and Clinical Outcome in MPS II Patients Receiving Iduronate-2-Sulfatase Enzyme Replacement Therapy, funded by Transkaryotic Therapies Inc., Cambridge, MA, J. Muenzer, P.I., $584,856 (30% effort).

2005-2007 An Open-Label Maintenance Clinical Study of Iduronate-2-Sulfatase Replacement Therapy in Patients with MPS II, funded by Transkaryotic Therapies Inc., Cambridge, MA, J. Muenzer, P.I., $438,062 (30% effort).

2003-2005 The Natural History of Mucopolysaccharidosis II (MPS II) an International, Multicenter, Longitudinal Observational Study, funded by Transkaryotic Therapies Inc., Cambridge, MA, J. Muenzer, P.I., $618,414.

2003-2005 A Phase II/III, Randomized, Double-Blind, Placebo-Controlled Clinical Study Evaluating the Safety and Efficacy of Weekly and Bi-weekly Dosing Regimens of Iduronate-2-Sulfatase Enzyme Replacement Therapy in Patients with MPS II, funded by Transkaryotic Therapies Inc., Cambridge, MA, J. Muenzer, P.I., $705,106.

2002-2004 An Open-Label Maintenance Clinical Study of Iduronate-2-Sulfatase Replacement Therapy in Patients with MPS II, funded by Transkaryotic Therapies Inc., Cambridge, MA, J. Muenzer, P.I., $576,031.

2001-2004 Phase I/II, Randomized, Double-Blind, Placebo-Controlled, Multiple Dose, Dose Escalation, Safety and Clinical Activity Study of Iduronate-2- Sulfatase Replacement Therapy in Patients with MPS II, funded by Transkaryotic Therapies Inc., Cambridge, MA, J. Muenzer, P.I., $546,824

2001-2003 A Multicenter, Multinational, Open-Label Extension Study of Safety and Efficacy of Recombinant Human Alpha-L-Iduronidase in Patients with Mucopolysaccharidosis I, funded by BioMarin-Genzyme, J. Muenzer, P.I., $264,552

2000-2001 Randomized, Double-Blind, Placebo-Controlled, Multicenter, Multinational, Clinical Study of Recombinant Human Alpha-L-

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Iduronidase in Patients with Mucopolysaccharidosis I, funded by BioMarin-Genzyme, J. Muenzer, P.I., $439,448

2000-2002 2000-2001 Neurological correction of MPS by AAV gene therapy, funded by the Children’s Medical Research Foundation, Inc., Western Springs, IL, J. Muenzer, P.I., $102,464.

2000-2001 1999-2000 Neurological correction of MPS by AAV gene therapy, funded by the Children’s Medical Research Foundation, Inc., Western Springs, IL, J. Muenzer, P.I., $71,594.

1997-1998 Neurological correction of MPS by AAV gene therapy, funded by the Children’s Medical Research Foundation, Inc., Western Springs, IL, J. Muenzer, P.I., $109,223.

1997-1998 MPS II mouse model, J. Muenzer, P.I., UNC Medical School grant for pilot research for gene therapy funded by Howard Hughes foundation, $50,000.

1996 - 1997 Unrecognized Maternal Hyperphenylalaninemia; A Possible Cause of Mental Retardation, D. Frazier and J. Muenzer, co P.I., Frank Porter Graham grant, $6,320

1992 National Medical Fellowships, Inc., Laboratory expenses for a Academic Medicine Research Fellowship for a Minority Student

1987 - 1992 Molecular Genetics of Iduronate Sulfatase Deficiencies, J. Muenzer, P.I. (5R29 DK38383-05), $70,140/year

1987 - 1990 Tetrahydrobiopterin Treatment of Biopterin Deficiency; J. Muenzer, P.I.,$68,611/ year

7) Professional Service:

2015 – present Chair, Hunter Outcome Survey Executive Committee Shire Human Genetics Therapies, Inc.

2013 – present Member, Shire’s Medical Expert Committee (philanthropy program for enzyme replacement).

2009 – 2014 Chair, Hunter Outcome Survey Executive Committee Shire Human Genetics Therapies, Inc.

2008 - 2016 Chair, International MPS I Registry Board of Advisors

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2008 – 2009 Member, Hunter Outcome Survey Executive Committee Shire Human Genetics Therapies, Inc.

2008 – 2010 Chair, Fabry Independent Scientific Oversight Committee (ISOC) Canadian Institutes of Health Research Ottawa, Ontario

2007 - 2007 Member, Laboratory Medicine Practice Guideline Committee on Expanded Newborn Screening by Tandem Mass Spectrometry and Follow-Up Testing National Academy of Clinical Biochemistry

2006 - 2008 Co-chair, Southeastern Region Genetics Group (SERGG) Laboratory Workgroup

2005 - present Member, Hunter Syndrome International Advisory Board Shire Human Genetics Therapies, Inc.

2005 - 2010 Research Consultant Shire Human Genetics Therapies, Inc.

2004 - present Member, US Lysosomal Disease Network

2004 - 2008 Member, Hunter Outcome Survey Advisory Board Shire Human Genetics Therapies, Inc.

2003 - 2009 Chair, North American MPS I Registry Board

2003 - present Member, International MPS I Registry Board of Advisors

2003 - present Member, MPS I Expert Panel BioMarin and Genzyme

2003 – 2004 Member, North Carolina Task Force on Genomics and Public Health

2002 Participant, Planning and Implementation Meeting for the Global Organization for Lysosomal Disorders, Cannes, France February 7-9, 2002.

2002 - 2005 Medical Advisor International Morquio Organization

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J. Muenzer, M.D., Ph.D.

1996 - present Chair State of North Carolina Newborn Screening Advisory Committee

1999 - 2005 Research Consultant Transkaryotic Therapies, Inc., Boston, MA

1998 – 2003 Chair Scientific Advisory Board, National MPS Society

1995 - present Medical Consultant State of North Carolina Newborn Screening Program

1995 - 1996 Member North Carolina Newborn Screening Advisory Committee

1991 - 1994 Scientific Review Committee Storage Disease Collaborative Study Group A study of value of bone marrow transplantation for storage diseases 1R0I NS 29099

1987 - 1990 Health Professional Advisory Council and Medical Services Subcommittee Southeast Michigan Chapter, March of Dimes

1987 - present Member Scientific Advisory Board, National MPS Society

1987 - 1993 Member, Genetics Advisory Committee Michigan Department of Public Health

University of North Carolina at Chapel Hill:

1997 – 2011 Assistant Director, Pediatric Metabolic Screening Laboratory, UNC Hospitals Clinical Chemistry

1995 - 2010 Member Meds/Peds Residency Selection Committee

1994 -1997 Consultant Pediatric Metabolic Screening Laboratory, UNC Hospitals Clinical Chemistry

1993 - 2010 Director Biochemical Genetics and Metabolism Laboratory, Division of Genetics and Metabolism

8) Research Statement:

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J. Muenzer, M.D., Ph.D.

My clinical research has focused on developing new treatments for patients with mucopolysaccharidosis (MPS). I have become a national referral center for the management and treatment of patients with MPS. I have seen in the last five years >120 patients with Hunter syndrome (MPS II) which is >1/4 of the estimated 400 to 450 MPS II patients in North American. I am currently recognized as an international expert in the management and treatment of patients with MPS. I am routinely asked to speak at national and international meetings about the diagnosis, management and treatment of MPS disorders and chair and/or serve on international MPS advisory boards. My initial clinical research focused on developing intravenous enzyme replacement therapy for patients with MPS I and MPS II. I was a principal investigator for the phase I/II and phase III intravenous enzyme replacement clinical trials for MPS I resulting in the approval of Aldurazyme in 2003. I was the principal investigator for the initial phase I/II intravenous enzyme replacement clinical trials for MPS II and was considered the lead-investigator for the multi-centered international phase II/III intravenous enzyme replacement clinical trials for Elaprase, which was approved in 2006. Although enzyme replacement therapy has become a reality for the prevention of somatic disease progression in MPS I and MPS II, the blood-brain barrier prevents the IV administered enzyme from entering the brain and impacting the progressive neurological disease seen in the severe forms of MPS II. In the last seven years, I have been involved in designing and implementing both a phase I/II and phase II/III intrathecal enzyme replacement clinical trials for the severe form of MPS II. The goal of the phase I/II clinical trial was to determine the safety and efficacy of monthly administration of intrathecal recombinant enzyme administered using an intrathecal drug delivery device. The one year pivotal multinational phase II/III intrathecal clinical trial has completed enrollment in late September 2016 with results available late 2017. I also have been a principal investigator for a phase IIB intrathecal clinical trial for Sanfilippo A syndrome (MPS IIIA). I am currently in the planning stages to start at least four phase I/II gene therapy clinical trials for MPS I, MPS II and MPS IIIA. The gene therapy trials will be a combination of industry sponsored and investigator initiated studies. In summary, my clinical research for the last seven years has focus on developing treatment for the brain disease in patients with different forms of mucopolysaccharidosis (MPS) using intrathecal enzyme replacement therapy, but I will be soon starting gene therapy clinical trials as another means to treat the physical and central nervous system disease in MPS patients. I am privileged to work in an academic environment that foster excellent patient care and promotes translational clinical research.

10) Teaching Statement:

As a physician scientist, my teaching responsibilities are as varied as the different aspects of my academic role in a major research university/medical center. As a pediatric subspecialist in the rapidly changing field of genetics, I am actively involved in the education of medical students, pediatric residents/fellows, genetic counseling students, genetic residents/fellows, pathology residents/fellows, parents of my pediatric patients and my adult patients with metabolic disorders. I am involved in teaching medical students and pediatric residents who are assigned to our genetics and metabolism outpatient clinic or metabolic consult service. When I have seen a metabolic patient with a trainee, I will typically review the metabolic pathways and treatment concepts after clinic visit is completed. I have found that these teaching sessions are very valuable to the students and residents. For most students and residents it was their first encounter with the rare disorder and for which they now have a new understanding of the disease etiology and treatment principles. I try to emphasize how the disorder may present to them in their future clinical practices and the need for early recognition for optimal long-term outcome.

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J. Muenzer, M.D., Ph.D.

As a pediatric biochemical geneticist, I have frequent encounters with patients and their families with complex and usually very rare inborn errors of metabolism. With these patients, I feel very strongly that the patents and/or parents needs to have as much of an understanding of nature of the disease and treatment options and plans as they can possible comprehend. It is my stated goal to families and patients that they need to have more knowledge than virtually every health care provider they encounter to optimize their child’s health care. I strongly believe that my patients and their families need to know the cause of their disorder, possible outcomes, treatment and management issues explained to them in a medical correct manner, but as detailed as possible. I will routinely modify an explanation of a problem to match the education level and degree of medical sophistication of the family. On repeat clinic visits, I will usually ask the parents or patient to explain in their own word, not mine, as much as they can understand about their disorder, prognosis and treatment. Based on their understanding, I will continue my teaching about the disorder at the level where they may not have been correct or lacked what I consider to be an adequate understanding. As one example, I insist that parents be able to say the correct name of their child’s disorder, such as “3-methylcrotonyl- glycinuria” (an organic aciduria due to abnormal metabolism of the amino acid leucine) and not that my child has an “acid” problem. Teaching families about their medical condition is a never ending process since medical knowledge and my understanding is always expanding from proposed new treatment options to new insights about pathophysiology. I encourage families to share their information with their many health care providers, because if the family members can become the teachers their own understanding is enhanced.

One of my greatest teaching challenges is to demonstrate to medical students and pediatric residents/fellows that biochemistry is not as complex or tedious as they believed from the first two years of medical school. My patients with inborn errors of metabolism (biochemistry) are my best handouts. To explain that the metabolic disorder they are confronting is usually due to a block in a metabolic cycle or pathway and that knowing that information can lead to a logical beneficial treatment plan is very enlightening and stimulating to medical students and pediatric residents. Now instead of envisioning learning about a biochemical pathway as a boring assignment, their new knowledge of biochemistry can spring to life to improve the care of an infant and usually results in tremendous clinical benefit and professional satisfaction. One of my rewards in teaching medical students, pediatric housestaff and fellows is that I am constantly challenged to explain biochemistry in a straightforward and useful manner. I sometimes feel like I benefit more from teaching, than the medical students or pediatric residents that I teach. As medical students and pediatric residents ask complex questions about metabolic pathways/disorders, I am challenged to read more to continue to improve my understanding and thereby improving my role as a teacher. Although I do not spend as much time devoted to teaching as I once did, my teaching responsibilities are still a great source of my academic satisfaction.

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