Education/Training:
1969 University of Naples - Ph.D. in Biological Sciences (110/110 cum laude)
1992 University of Naples Federico II, Medical Degree (110/110 cum laude)

Employment and Experience:
1973/1976 NIH - Bethesda, MD, USA - Visiting Associate
1976/1979 II Medical School, University of Naples, Assistant Professor
1980/1986 II Medical School, University of Naples, Associate Professor
1982 to date University of Naples Federico II - Member of the Council for Ph.D. Course in Genetics
1984 EMBL - Heidelberg, Germany - Guest Worker
1984/1986 University of Naples - Director of the Institute of Cellular and Molecular Biochemistry
1986/1989 Medical School of Catanzaro, University of Reggio Calabria - Full Professor of Biochemistry
1989 to date Medical School, University of Naples Federico II - Full Professor of Biochemistry

Membership to Scientific Societies
European Study Group on Lysosomal Diseases (ESGLD): member of the scientific advisors from 1997 to date
Society for the Study of Inborn Errors of Metabolism
Italian Society for the Study on Inborn Errors of Metabolism:
1984, Member of Directory; 1986, Vicepresident; 1989-1993, President
Italian Society of Biochemistry

Invitation to Congresses as speaker or chairperson:

Scientific Committees
National Congress of the Italian Federation for the Study of Inherited Diseases (FISME):
VI National Congress FISME, Parma, 16-19 September 1991
VII National Congress FISME, Genova 25-28 November 1992
VIII National Congress FISME, Sorrento 7-10 November 1993
Member of the Advisory Board of the 5th International Symposium on Mucopolysaccharide and Related Diseases, Vienna, Austria, March 18-21, 1999
Member of the Advisory Board of the 13th Workshop of European Study Group on Lysosomal Diseases (ESGLD), Woudschoten, The Netherlands, September 20-23 2001
Member of the Advisory Board of the Internatinal Symposium on Mucopolysaccharide and related Diseases, Parigi, Francia, June 20-23, 2002
Member of the Advisory Board of the14th Workshop of European Study Group on Lysosomal Diseases (ESGLD), Podebrady, Czech Republic, September 18-21 2003
Member of the Advisory Board of the15th Workshop of European Study Group on Lysosomal Diseases (ESGLD), Oslo, Norway, September 15-18 2005
- Member of the Advisory Board of the 9th International Symposium on Mucopolysaccharide and Related Diseases, Venice, June 29- July 2, 2006
- Member of the Advisory Board of the 16th Workshop of European Study Group on Lysosomal Diseases (ESGLD), Perugia, Italy, September 27-30 2007
- Member of the Advisory Board of the 17th Workshop of European Study Group on Lysosomal Diseases (ESGLD), Bad Honnef, Germany, September 10-13, 2009

Referee of the following journals:
Biochimica et Biophysica Acta
Clinical Genetics
Human Genetics
Human Mutation
Journal of Inherited Metabolic Disease
Journal of Medical Genetics
Pediatric Research

The research activity of the laboratory will focus on testing the efficacy of substrate reduction therapy (SRT) with a small molecule drug, for the treatment of mucopolysaccharidosis IIIB (MPS IIIB). Preliminary experiments showed that a xylose analogue (referred to as MXP) interferes with the synthesis of glycosaminoglycans (GAGs) and proteoglycans (PGs) and reduces substrate storage in MPS IIIB fibroblasts.
The experimental plan will be performed in the MPS IIIB murine model, already available in our laboratory. The specific aims of the project will be:
1. to complete the studies on the effects of MXP in vivo. Particular attention will be paid to the therapeutic effects of MXP in the central nervous system;
2. to identify the optimal MXP dosage that is able to reduce substrate storage;
3. to study MXP distribution in body tissues and organs. Specifically, we will test the ability of MXP to cross the blood-brain barrier and reach therapeutic concentrations in the central nervous system;
4. to evaluate age dependency of MXP therapeutic effects and the possibility that MXP may at least in part revert initial neurological involvement;
5. to test MXP efficacy in other mucopolysaccharidoses. The effect of MXP will be tested in cultured fibroblasts from patients with these disorders and in the animal model of MPS IIIA, that is under evaluation by a collaborating group.

Tomatsu S, Sukegawa K, Trandafirescu GG, Gutierrez MA, Nishioka T, Yamaguchi S, Orii T, Froissart R, Maire I, Chabas A, Cooper A, Di Natale P, Gal A, Noguchi A, Sly WS (2006) Differences in methylation patterns in the methylation boundary region of IDS gene in hunter syndrome patients: implications for CpG hot spot mutations. Eur J Hum Genet 14(7):838-845

Di Domenico C, Di Napoli D, Gonzalez y Reyero E, Lombardo A, Naldini L, Di Natale P (2006) Limited transgene immune response and long-term expression of human -L-iduronidase in young adult mice with Mucopolysaccharidosis type I by liver-directed gene therapy. Hum Gene Ther 17:1112-1121

Villani GRD, Gargiulo N, Faraonio R, Castaldo S, Gonzalez y Reyero E, Di Natale P (2007) Cytokines, neurotrophins and oxidative stress in brain disease from mucopolysaccharidosis IIIB. J Neurosci Res 85:612-622

Montano AM, Sukegawa K, Kato Z, Carrozzo R, Di Natale P, Christensen E, Orii KO, Orii T, Kondo N, Tomatsu S (2007) Effect of "attenuated" mutations in mucopolysaccharidosis IVA on molecular phenotypes of N-acetylgalactosamine-6-sulfate sulfatase. J. Inherit. Metab. Dis. 30, 758-767

Fedele A.O., Filocamo M., Di Rocco M., Sersale G., Lübke T., Di Natale P., Cosma M.P., Ballabio A. (2007) Mutational analysis of the HGSNAT gene in Italian patients with mucopolysaccharidosis IIIC (Sanfilippo C Syndrome). Hum Mutat Mutation in Brief #959, online

Di Natale P, Villani GR, Parini R, Scarpa M, Parenti G, Pontarelli G, Grosso M, Sersale G, Tomanin R, Sibilio M, Barone R, Fiumara A (2008) Molecular markers for the follow-up of enzyme replacement therapy in mucopolysaccharidosis VI disease. Biotechnol Appl Biochem 49:219-223

Concolino D, Muzzi G, Pisaturo L, Piccirillo A, Di Natale P, Strisciuglio P (2008) Precocious puberty in Sanfilippo IIIA disease: diagnosis and follow-up of two new cases. Eur J Med Genet 51(5):466-471

Villani GR, Di Domenico C, Musella A, Cecere F, Di Napoli D, Di Natale P (2009) Mucopolysaccharidosis IIIB: oxidative damage and cytotoxic cell involvement in the neuronal pathogenesis. Brain Res 7:1279-1299

Di Domenico C, Villani GR, Di Napoli D, Nusco E, Calì G, Nitsch L, Di Natale P (2009) Intracranial gene delivery of LV-NAGLU vector corrects neuropathology in murine MPS IIIB. Am J Med Genet A 149A(6):1209-1218

Di Natale P, Di Domenico C, Di Napoli D (2010) Serum MIP-1 level: a biomarker for the follow-up of lentiviral therapy in mucopolysaccharidosis IIIB mice. J Inherit Metab Dis 33:159-165

Visigalli I, Delai S, Politi LS, Di Domenico C, Cerri F, Mrak E, D'Isa R, Ungaro D, Stok M, Sanvito F, Mariani E, Staszewsky L, Godi C, Russo I, Cecere F, Del Carro U, Rubinacci A, Brambilla R, Quattrini A, Di Natale P, Ponder K, Naldini L, Biffi A (2010) Gene therapy augments the efficacy of hematopoietic cell transplantation and fully corrects Mucopolysaccharidosis type I phenotype in the mouse model. Blood 116(24):5130-5139

Cecere F, Di Domenico C, Di Napoli D, Boscia F, Di Natale P (2011) Activation of stress kinases in the brain of mucopolysaccharidosis IIIB mice. J Neurosci Res doi: 10.1002/jnr.22674 [Epub ahead of print]

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