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Dose responsive effects of subcutaneous pentosan polysulfate injection in mucopolysaccharidosis type VI rats and comparison to oral treatment.
Frohbergh, Michael; Ge, Yi; Meng, Fanli; Karabul, Nesrin; Solyom, Alexander; Lai, Alon; Iatridis, James; Schuchman, Edward H; Simonaro, Calogera M.
Afiliação
  • Frohbergh M; Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
  • Ge Y; Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
  • Meng F; Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
  • Karabul N; Department of Pediatrics, University of Mainz, Mainz, Germany.
  • Solyom A; Department of Pediatrics, University of Mainz, Mainz, Germany; Department of Pediatrics, University of Pécs, Pécs, Hungary.
  • Lai A; Orthopedics, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
  • Iatridis J; Orthopedics, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
  • Schuchman EH; Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
  • Simonaro CM; Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
PLoS One ; 9(6): e100882, 2014.
Article em En | MEDLINE | ID: mdl-24964042
BACKGROUND: We previously demonstrated the benefits of daily, oral pentosan polysulfate (PPS) treatment in a rat model of mucopolysaccharidosis (MPS) type VI. Herein we compare these effects to once weekly, subcutaneous (s.c.) injection. The bioavailability of injected PPS is greater than oral, suggesting better delivery to difficult tissues such as bone and cartilage. Injected PPS also effectively treats osteoarthritis in animals, and has shown success in osteoarthritis patients. METHODOLOGY/PRINCIPAL FINDINGS: One-month-old MPS VI rats were given once weekly s.c. injections of PPS (1, 2 and 4 mg/kg, human equivalent dose (HED)), or daily oral PPS (4 mg/kg HED) for 6 months. Serum inflammatory markers and total glycosaminoglycans (GAGs) were measured, as were several histological, morphological and functional endpoints. Overall, weekly s.c. PPS injections led to similar or greater therapeutic effects as daily oral administration. Common findings between the two treatment approaches included reduced serum inflammatory markers, improved dentition and skull lengths, reduced tracheal deformities, and improved mobility. Enhanced effects of s.c. treatment included GAG reduction in urine and tissues, greater endurance on a rotarod, and better improvements in articular cartilage and bone in some dose groups. Optimal therapeutic effects were observed at 2 mg/kg, s.c.. No drug-related increases in liver enzymes, coagulation factor abnormalities or other adverse effects were identified following 6 months of s.c. PPS administration. CONCLUSIONS: Once weekly s.c. administration of PPS in MPS VI rats led to equal or better therapeutic effects than daily oral administration, including a surprising reduction in urine and tissue GAGs. No adverse effects from s.c. PPS administration were observed over the 6-month study period.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Métodos Terapêuticos e Terapias MTCI: Terapias_biologicas / Aromoterapia Assunto principal: Poliéster Sulfúrico de Pentosana / Mucopolissacaridose VI Tipo de estudo: Prognostic_studies Idioma: En Revista: PLoS One Ano de publicação: 2014 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Base de dados: MEDLINE Métodos Terapêuticos e Terapias MTCI: Terapias_biologicas / Aromoterapia Assunto principal: Poliéster Sulfúrico de Pentosana / Mucopolissacaridose VI Tipo de estudo: Prognostic_studies Idioma: En Revista: PLoS One Ano de publicação: 2014 Tipo de documento: Article País de afiliação: Estados Unidos