Calogera M. Simonaro
- ASSOCIATE PROFESSOR Genetics and Genomic Sciences
B.A., St. John's University
M.S., Brooklyn College
Ph.D., New York University
Mount Sinai School of Medicine
M.Ph., New York University
ResearchEnzyme replacement studies in MPS animals and human patients have revealed that chondrocytes in joints and bones are difficult to reach following injection due to the poor vascular supply to these tissues and the fact that the target cells are embedded in a dense matrix. With the availability of enzyme replacement it is important to continue to investigate new approaches for improving enzyme delivery to these critical target tissues.
Our findings have important implications for the treatment of MPS individuals, as well as for the identification of novel biomarkers to monitor disease progression and therapeutic efficacy. In addition, many of the pathologic processes in the MPS bones and joints have close similarities to those that occur in arthritis. Thus, some of the important biomarkers and therapeutic targets for arthritis should be considered for MPS.The overall goal of our research is to fill the void in our understanding of MPS bone and joint disease and to develop new and improved therapies that might benefit MPS patients. We specifically study two animal models with MPS VI, but anticipate that the results obtained can be applicable to the general class of MPS disorders and benefit a wide range of patients.
Our studies carried out over the past five years have revealed that glycosaminoglycan GAG accumulation is a direct cause of chondrocyte death (apoptosis) in the articular cartilage and growth plates of MPS animals, leading to abnormal matrix homeostasis. This enhanced cell death also triggers a series of signaling events that lead to marked inflammatory disease with characteristic increases in proinflammatory cytokines, metalloproteinases (MMPs), and apoptotic cells. Together, these two factors (enhanced cell death and inflammation), lead to the characteristic bone and joint disease in the MPS disorders. In addition, cellular defects associated with the maturation of MPS growth plates are likely contributing to abnormal bone growth.
Simonaro C, D'Angelo M, Haskins M, Schuchman E, Eliyahu E, Shtraizent N, HE X. Mechanism of Glycosaminoglycan-Mediated Bone & Joint Disease: Implications for the Mucopolysaccharidoses & Other Connective Tissue Diseases. Amer J Path 2008; 172(1): 112-122.
Simonaro CM, Park JH, Schuchman EH, Shtraizent N, Mcgovern M, Eliyahu E. Imprinting at the SMPD-1 locus: Implications for acid sphingomyelinase deficient Niemann-Pick disease. Am. J. Hum. Gen 2006; 70: 79-84.
Simonaro CM, Schuchman EH, Haskins ME, D'Angelo M. Joint and bone disease in the mucopolysaccharidoses: Identification of new therapeutic targets and biomarkers using animal models. Ped. Res 2005; 57: 701-707.
Simonaro CM, Desnick RJ, Schuchman EH, Wasserstein MP, Mcgovern MM. The demographics and distribution of Type B Niemann-Pick disease: Novel mutations lead to new genotype/phenotype correlations. Am. J. Hum. Gen 2002; 71: 1413-1419.
Li CM, Park JH, Simonaro CM, He X, Gordon RE, Haimovitz-Friedman A, Schuchman EH, Paris F, Manova K, Fuks Z, Kolesnick R, Sandoff K, Ehleriter A. Disruption of the mouse acid ceramidase gene leads to early embryonic lethality in homozygotes and lipid storage disease in heterozygotes. Genomics 2002; 79: 218-224.
Simonaro CM, Haskins ME, Schuchman EH. Articular chondrocytes from animals with a dermatan sulfate storage disease undergo a high rate of apoptosis and release nitric oxide and inflammatory cytokines: a possible mechanism underlying degenerative joint disease in the Mucopolysaccharidoses. Lab Invest 2001; 81: 1319-1328.
Physicians and scientists on the faculty of the Icahn School of Medicine at Mount Sinai often interact with pharmaceutical, device and biotechnology companies to improve patient care, develop new therapies and achieve scientific breakthroughs. In order to promote an ethical and transparent environment for conducting research, providing clinical care and teaching, Mount Sinai requires that salaried faculty inform the School of their relationships with such companies.
Below are financial relationships with industry reported by Dr. Simonaro during 2012 and/or 2013. Please note that this information may differ from information posted on corporate sites due to timing or classification differences.
- BioMarin Pharmaceutical Inc.
Mount Sinai's faculty policies relating to faculty collaboration with industry are posted on our website at http://icahn.mssm.edu/about-us/services-and-resources/faculty-resources/handbooks-and-policies/faculty-handbook. Patients may wish to ask their physician about the activities they perform for companies.
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