Synageva BioPharma Corp. (Synageva) (NASDAQ:GEVA), a biopharmaceutical company developing therapeutic products for rare diseases, today announced SBC-103 data from an oral and poster presentation at the LDN WORLD Symposium being held February 11-13 in San Diego, California. Synageva is investigating SBC-103 as an enzyme replacement for the alpha-N-acetyl-glucosaminidase (NAGLU) enzyme for mucopolysaccharidosis IIIB (MPS IIIB, also known as Sanfilippo B syndrome). MPS IIIB is caused by a decrease in NAGLU enzyme activity which leads to the buildup of abnormal amounts of heparan sulfate in the brain and other organs. The SBC-103 preclinical data presented at the meeting confirms results from previous studies, describes a potential mechanism for central nervous system uptake, and supports further clinical investigation of SBC-103 with intravenous administration.
As part of an oral presentation, Sandra Rojas-Caro, MD, Head of Clinical Research and Development at Synageva presented data from a preclinical study with SBC-103 in a mouse model of MPS IIIB. Data from this study confirmed that SBC-103 delivered by intravenous and intrathecal administration reduced abnormal heparan sulfate levels in the brain of NAGLU-deficient mice. In addition, intravenously administered SBC-103 increased NAGLU enzyme activity levels in the brain of a MPS IIIB mouse model and increased cerebral spinal fluid NAGLU enzyme activity in non-human primates in preclinical studies. These findings suggest that SBC-103 may have properties that allow it to cross the normal blood-brain barrier.
Additional data supporting this observation was provided as a poster from a study that investigated SBC-103 in an in vitro model of the blood-brain barrier. In this study, SBC-103 was effectively transported from the apical side (representing the blood) to the opposite basolateral side (representing the brain tissue). The addition of mannose-6-phospate inhibited directional transport by more than 90%, suggesting that the observed transport of SBC-103 was mediated by the mannose-6-phosphate receptor. These data suggest that the previously reported effects of intravenous SBC-103 on central nervous system substrate accumulation in an MPS IIIB disease model may be mediated by specific cellular transport across the blood-brain barrier.