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Paola Leone, Ph.D.


Science Center 253


University of Padua, Ph.D. (Neuroscience), 1987

Research Interests

I have many years of experience in translational/clinical neuroscience research and my longstanding research commitments are centered into identifying the pathophysiologic mechanisms underlying neurodegenerative diseases, characterize and promote brain repair mechanisms and prevent disease progression in patients. During the past decade I have implemented preclinical and/or clinical applications of novel therapeutics to Canavan Disease, Amyotrophic Lateral Sclerosis, Alzheimer’s Disease, Multiple Sclerosis and Traumatic Brain Injury. Specifically, I have developed preclinical and clinical applications of novel therapeutics to Canavan Disease and these have changed the current clinical management and outcome of newly diagnosed patients with Canavan Disease. My laboratory is currently undertaking several lines of investigation: 1) We are conducting studies to assess the targeted and comprehensive analysis of the potential of cell based therapy for White Matter Diseases 2) We are analyzing the phenotype and polyfunctionality of peripheral cells in Multiple Sclerosis patients, and are correlating these parameters with Multiple Sclerosis forms, therapies and disease progression. This research may have future implications for predicting Multiple Sclerosis form and progression as well as for the selection of therapeutic interventions  3) We are generating preclinical data to assess the potential clinical application of a metabolic therapy for Canavan patients  4) We are testing a neuroprotective strategy designed to support metabolic energy and promote cell survival and recovery in neurodegenerative diseases as well as Traumatic Brain Injury. These ongoing studies will provide proof of principle evidence for an extremely novel therapeutic intervention of potential relevance to a broad range of neurodegenerative diseases. 


(Updated January 2017)

  1. Francis JS, Wojtas I, Markov V, Gray SJ, McCown TJ, Samulski RJ, Bilaniuk LT, Wang DJ, De Vivo DC, Janson CG, Leone PN-acetylaspartate supports the energetic demands of developmental myelination via oligodendroglial aspartoacylaseNeurobiol Dis, 96: 323-34, December 2016.
  2. Zaroff S, Leone P, Markov V, Francis JS. Transcriptional regulation of N-acetylaspartate metabolism in the 5xFAD model of Alzheimer's disease: Evidence for neuron-glia communication during energetic crisis.Mol Cell Neurosci, 65: 143-152, March 2015.
  3. Kantor B, McCown T, Leone P, Gray SJ. Clinical applications involving CNS gene transfer. Adv Genet, 87: 71-124, October 2014.
  4. Gautier EL, Ivanov S, Williams JW, Huang SC, Marcelin G, Fairfax K, Wang PL, Francis JS, Leone P, Wilson DB, Artyomov MN, Pearce EJ, Randolph GJ. Gata6 regulates aspartoacylase expression in resident peritoneal macrophages and controls their survival. J Exp Med, 211(8): 1525-31, July 2014
  5. Francis JS, Markov V, Leone PDietary triheptanoin rescues oligodendrocyte loss, dysmyelination and motor function in the nur7 mouse model of Canavan disease. J Inherit Metab Dis, 37(3): 369-81, May 2014.
  6. Assadi M, Wang DJ, Rodriguez Y, Leone PMulti-Voxel 1H-MRS in Metachromatic Leukodystrophy.  J Cent Nerv Syst Dis, 5: 25-30, July 2013.
  7. Leone P, Shera D, McPhee SW, Francis JS, Kolodny EH, Bilaniuk LT, Wang DJ, Assadi M, Goldfarb O, Goldman HW, Freese A, Young D, During MJ, Samulski RJ, Janson CG. Long-term follow-up after gene therapy for canavan disease. Sci Transl Med, 19:4(165), 1-13, Dec 2012.
  8. Francis JS, Strande L, Markov V, Leone PAspartoacylase supports oxidative energy metabolism during myelination. J Cereb Blood Flow Metab, 32(9): 1725-36, Sep 2012.
  9. Francis JS, Strande L, Pu A, Leone PEndogenous aspartoacylase expression is responsive to glutamatergic activity in vitro and in vivo. Glia, 59(10): 1435-46, Oct 2011.
  10. Assadi M, Janson C, Wang DJ, Goldfarb O, Suri N, Bilaniuk L, Leone PLithium citrate reduces excessive intra-cerebral N-acetyl aspartate in Canavan disease. Eur J Paediatr Neurol, 14(4): 354-9, Jul 2010.
  11. Wang J, Leone P, Wu G, Francis JS, Li H, Jain MR, Serikawa T, Ledeen RW. Myelin lipid abnormalities in the aspartoacylase-deficient tremor rat. Neurochem Res, 34(1):138-48, Jan 2009.
  12. Assadi M, Leone P, Veloski JJ, Schwartzman RJ, Janson CG, Campellone JV. Validating an Ataxia Functional Composite Scale in spinocerebellar ataxia. J Neurol Sci, 15; 268(1-2): 136-9, May 2008.
  13. Assadi M, Baseman S, Janson C, Wang DJ, Bilaniuk L, Leone PSerial 1H-MRS in GM2 gangliosidoses. Eur J Pediatr, 167(3):347-52, Mar 2008.
  14. Aghai ZH, Faqiri S, Saslow JG, Nakhla T, Farhath S, Kumar A, Eydelman R, Strande L, Stahl G, Leone P, Bhandari V. Angiopoietin 2 concentrations in infants developing bronchopulmonary dysplasia: attenuation by dexamethasone. J Perinatol, 28(2): 149-55, Feb 2008.
  15. Aghai ZH, Kode A, Saslow JG, Nakhla T, Farhath S, Stahl GE, Eydelman R, Strande L, Leone P, Rahman I. Azithromycin suppresses activation of nuclear factor-kappa B and synthesis of pro-inflammatory cytokines in tracheal aspirate cells from premature infants. Pediatr Res, 62(4):483-8, Oct 2007.
  16. Assadi M, Campellone JV, Janson CG, Veloski JJ, Schwartzman RJ, Leone PTreatment of spinocerebellar ataxia with buspirone. J Neurol Sci, 260(1-2):143-6, Sep 2007.
  17. Francis JS, Olariu A, Kobayashi E, Leone PGFP-transgenic Lewis rats as a cell source for oligodendrocyte replacement. Exp Neurol, 205(1): 177-89, May 2007.
  18. Zeng BJ, Wang ZH, Torres PA, Pastores GM, Leone P, Raghavan SS, Kolodny EH. Rapid detection of three large novel deletions of the aspartoacylase gene in non-Jewish patients with Canavan disease. Mol Genet Metab, 89(1-2): 156-63, Sep 2006.
  19. Zeng BJ, Pastores GM, Leone P, Raghavan S, Wang ZH, Ribeiro LA, Torres P, Ong E, Kolodny EH. Mutation analysis of the aspartoacylase gene in non-Jewish patients with Canavan disease. Adv Exp Med Biol, 576:165-73, 2006.
  20. Janson CG, McPhee SW, Francis J, Shera D, Assadi M, Freese A, Hurh P, Haselgrove J, Wang DJ, Bilaniuk L, Leone PNatural history of Canavan disease revealed by proton magnetic resonance spectroscopy (1H-MRS) and diffusion-weighted MRI. Neuropediatrics, 37(4): 209-21, Aug 2006.
  21. Francis JS, Olariu A, McPhee SW, Leone PNovel role for aspartoacylase in regulation of BDNF and timing of postnatal oligodendrogenesis. J Neurosci Res, 84(1): 151-69, Jul 2006.
  22. McPhee SW, Janson CG, Li C, Samulski RJ, Camp AS, Francis J, Shera D, Lioutermann L, Feely M, Freese A, Leone PImmune responses to AAV in a phase I study for Canavan disease. J Gene Med, 8(5): 577-88, May 2006.
  23. Janson CG, Kolodny EH, Zeng BJ, Raghavan S, Pastores G, Torres P, Assadi M, McPhee S, Goldfarb O, Saslow B, Freese A, Wang DJ, Bilaniuk L, Shera D, Leone PMild-onset presentation of Canavan's disease associated with novel G212A point mutation in aspartoacylase geneAnn Neurol, 59(2): 428-31, Feb 2006.
  24. Tavazzi B, Lazzarino G, Leone P, Amorini AM, Bellia F, Janson CG, Di Pietro V, Ceccarelli L, Donzelli S, Francis JS, Giardina B. Simultaneous high performance liquid chromatographic separation of purines, pyrimidines, N-acetylated amino acids, and dicarboxylic acids for the chemical diagnosis of inborn errors of metabolism. Clin Biochem, 38(11):997-1008, Nov 2005.
  25. Janson CG, Assadi M, Francis J, Bilaniuk L, Shera D, Leone PLithium citrate for Canavan disease.Pediatr Neurol, 33(4): 235-43, Oct 2005.
  26. McPhee SW, Francis J, Janson CG, Serikawa T, Hyland K, Ong EO, Raghavan SS, Freese A, Leone PEffects of AAV-2-mediated aspartoacylase gene transfer in the tremor rat model of Canavan disease. Brain Res Mol Brain Res, 135(1-2): 112-21, Apr 2005.
  27. Inoue H, Ohsawa I, Murakami T, Kimura A, Hakamata Y, Sato Y, Kaneko T, Takahashi M, Okada T, Ozawa K, Francis J, Leone P, Kobayashi E. Development of new inbred transgenic strains of rats with LacZ or GFP. Biochem Biophys Res Commun, 329(1):288-95, Apr 2005.
  28. Boulis NM, Noordmans AJ, Song DK, Imperiale MJ, Rubin A, Leone P, During M, Feldman EL. Adeno-associated viral vector gene expression in the adult rat spinal cord following remote vector delivery.Neurobiol Dis, 14(3): 535-41, Dec 2003.
  29. Zeng BJ, Wang ZH, Ribeiro LA, Leone P, De Gasperi R, Kim SJ, Raghavan S, Ong E, Pastores GM, Kolodny EH. Identification and characterization of novel mutations of the aspartoacylase gene in non-Jewish patients with Canavan disease. J Inherit Metab Dis, 25(7): 557-70, Nov 2002.
  30. Janson C, McPhee S, Bilaniuk L, Haselgrove J, Testaiuti M, Freese A, Wang DJ, Shera D, Hurh P, Rupin J, Saslow E, Goldfarb O, Goldberg M, Larijani G, Sharrar W, Liouterman L, Camp A, Kolodny E, Samulski J, Leone PClinical protocol. Gene therapy of Canavan disease: AAV-2 vector for neurosurgical delivery of aspartoacylase gene (ASPA) to the human brain. Hum Gene Ther, 13(11): 1391-412, Jul 2002.
  31. Abi-Saab WM, Maggs DG, Jones T, Jacob R, Srihari V, Thompson J, Kerr D, Leone P, Krystal JH, Spencer DD, During MJ, Sherwin RS. Striking differences in glucose and lactate levels between brain extracellular fluid and plasma in conscious human subjects: effects of hyperglycemia and hypoglycemia. J Cereb Blood Flow Metab, 22(3): 271-9, Mar 2002.
  32. Janson CG, McPhee SW, Leone P, Freese A, During MJ. Viral-based gene transfer to the mammalian CNS for functional genomic studies. Trends Neurosci, 24(12): 706-12, Dec 2001. Review.
  33. Janson CG, Ramesh TM, During MJ, Leone P, Heywood J. Human intrathecal transplantation of peripheral blood stem cells in amyotrophic lateral sclerosis. J Hematother Stem Cell Res, 10(6): 913-5, Dec 2001.
  34. Xu R, Janson CG, Mastakov M, Lawlor P, Young D, Mouravlev A, Fitzsimons H, Choi KL, Ma H, Dragunow M, Leone P, Chen Q, Dicker B, During MJ. Quantitative comparison of expression with adeno-associated virus (AAV-2) brain-specific gene cassettes. Gene Ther, 8(17): 1323-32, Sep 2001.
  35. Telfeian AE, Federoff HJ, Leone P, During MJ, Williamson A. Overexpression of GluR6 in rat hippocampus produces seizures and spontaneous nonsynaptic bursting in vitro. Neurobiol Dis, 7(4): 362-74, Aug 2000.
  36. Leone P, Janson CG, Bilaniuk L, Wang Z, Sorgi F, Huang L, Matalon R, Kaul R, Zeng Z, Freese A, McPhee SW, Mee E, During MJ. Aspartoacylase gene transfer to the mammalian central nervous system with therapeutic implications for Canavan disease. Ann Neurol, 48(1): 27-38, Jul 2000.
  37. Leone P, McPhee SW, Janson CG, Davidson BL, Freese A, During MJ. Multi-site partitioned delivery of human tyrosine hydroxylase gene with phenotypic recovery in Parkinsonian rats. Neuroreport, 11(6): 1145-51, Apr 2000.
  38. During MJ, Symes CW, Lawlor PA, Lin J, Dunning J, Fitzsimons HL, Poulsen D, Leone P, Xu R, Dicker BL, Lipski J, Young D. An oral vaccine against NMDAR1 with efficacy in experimental stroke and epilepsy. Science, 287(5457): 1453-60, Feb 2000.
  39. Leone P, Janson CG, McPhee SJ, During MJ. Global CNS gene transfer for a childhood neurogenetic enzyme deficiency: Canavan disease. Curr Opin Mol Ther, 1(4): 487-92, Aug 1999. Review.
  40. Young D, Lawlor PA, Leone P, Dragunow M, During MJ. Environmental enrichment inhibits spontaneous apoptosis, prevents seizures and is neuroprotective. Nat Med, 5(4): 448-53, Apr 1999.
  41. During MJ, Xu R, Young D, Kaplitt MG, Sherwin RS, Leone PPeroral gene therapy of lactose intolerance using an adeno-associated virus vector. Nat Med, 4(10): 1131-5, Oct 1998.
  42. During MJ, Samulski RJ, Elsworth JD, Kaplitt MG, Leone P, Xiao X, Li J, Freese A, Taylor JR, Roth RH, Sladek JR Jr, O'Malley KL, Redmond DE Jr. In vivo expression of therapeutic human genes for dopamine production in the caudates of MPTP-treated monkeys using an AAV vector. Gene Ther, 5(6): 820-7, Jun 1998.
  43. O'Connor WM, Davidson BL, Kaplitt MG, Abbey MV, During MJ, Leone P, Langer D, O'Connor MJ, Freese A. Adenovirus vector-mediated gene transfer into human epileptogenic brain slices: prospects for gene therapy in epilepsy. Exp Neurol, 148(1): 167-78, Nov 1997.
  44. Freese A, Kaplitt MG, O'Connor WM, Abbey M, Langer D, Leone P, O'Connor MJ, During MJ. Direct gene transfer into human epileptogenic hippocampal tissue with an adeno-associated virus vector: implications for a gene therapy approach to epilepsy. Epilepsia, 38(7): 759-66, Jul 1997.
  45. During MJ, Leone PTargets for gene therapy of Parkinson's disease: growth factors, signal transduction, and promoters. Exp Neurol, 144(1): 74-81, Mar 1997. Review.
  46. Maggs DG, Jacob R, Rife F, Lange R, Leone P, During MJ, Tamborlane WV, Sherwin RS. Interstitial fluid concentrations of glycerol, glucose, and amino acids in human quadricep muscle and adipose tissue. Evidence for significant lipolysis in skeletal muscle. J Clin Invest, 96(1): 370-7, Jul 1995.
  47. During MJ, Leone P, Davis KE, Kerr D, Sherwin RS. Glucose modulates rat substantia nigra GABA release in vivo via ATP-sensitive potassium channels. J Clin Invest, 95(5): 2403-8, May 1995.
  48. During MJ, Leone PAdeno-associated virus vectors for gene therapy of neurodegenerative disorders.Clin Neurosci, 3(5): 292-300, 1995-1996. Review.
  49. Kaplitt MG, Leone P, Samulski RJ, Xiao X, Pfaff DW, O'Malley KL, During MJ. Long-term gene expression and phenotypic correction using adeno-associated virus vectors in the mammalian brain. Nat Genet, 8(2): 148-54, Oct 1994.
  50. During MJ, Fried I, Leone P, Katz A, Spencer DD. Direct measurement of extracellular lactate in the human hippocampus during spontaneous seizures. J Neurochem, 62(6): 2356-61, Jun 1994.


1990-1992; Postdoctoral Research Fellow; Center for Studies in Behavioral Neurobiology, CONCORDIA UNIVERSITY, Montreal, Canada

1993–1996; Research Scientist, Dept of Neurosurgery, Gene Therapy & Neurogenetics Laboratories, YALE UNIVERSITY, New Haven, USA

1997–1998; Visiting Scientist, Gene Therapy Center, Dept of Molecular Medicine, UNIVERSITY OF AUCKLAND, Auckland, New Zealand

1998-2001; Assistant Professor, Dept of Neurosurgery, JEFFERSON MEDICAL COLLEGE, Philadelphia, PA, USA 

2002-2007; Associate Professor, Dept of Surgery & Dept of Molecular Genetics, Microbiology, & Immunology, UMDNJ/Robert Wood Johnson Medical School, Camden, NJ, USA

2002-2007; Adjunct Associate Professor, Dept of Neuroradiology, CHILDREN’S HOSPITAL OF PHILADELPHIA, Philadelphia, PA, USA

2007-June 2013; Associate Professor, Dept of Cell Biology, UMDNJ-School of Osteopathic Medicine, Stratford, NJ, USA

2007-June 2013; Director, Cell & Gene Therapy Center, UMDNJ-School of Osteopathic Medicine, Stratford, NJ, USA

July 2013-present; Associate Professor, Department of Cell Biology, ROWAN-School of Osteopathic Medicine, Stratford, NJ, USA

July 2013-present; Director, Cell & Gene Therapy Center, ROWAN-School of Osteopathic Medicine, Stratford, NJ, USA

Professional Memberships

  • American Society of Gene Therapy
  • European Society of Gene Therapy
  • American Society of Cell Biology
  • Brain Research Organization
  • Society for Neuroscience

Honors and Awards

  • 1999-UNESCO Young Investigator Award, Italy
  • 2003-Canavan Research Illinois, Scientist of the Year, USA
  • 2006-Woman of the Year, Lions Club, Italy
  • 2009-Foundation of UMDNJ's Excellence in Research Award, USA
  • 2010-Canavan Research Illinois, Scientific Achievement Award, USA
  • 2011, 2012-International Rare Disease Day, Hall of Fame
  • 2012-Edward J. III Medical Foundation Award in Biomedical Research, USA
  • 2013-American Academy of Neurology-NeuroFilm Festival 3rd Prize