Development and validation of therapy for mucopolysaccharidosis III

DESCRIPTION provided by applicant Sanfilippo syndrome mucopolysaccharidosis type III MPS III is a devastating neurodegenerative lysosomal storage disorder of childhood for which there is presently no cure or effective treatment available The fundamental cause of MPS III is an inherited mutation in one of the enzymes required to catabolize heparan sulfate HS a glycosaminoglycan which plays important structural and functional roles in the brain and elsewhere Each type of MPS III A through D is due to deficiency of a different enzyme in the HS breakdown pathway We now propose to develop an enzyme replacement treatment ERT for MPS III that will ameliorate or reverse the catastrophic and fatal neurologic decline caused by this disease As the symptoms of MPS III are largely localized to the brain any effective MPS III treatment must therefore gain access to the brain Therefore our strategy proposes to deliver recombinant human alpha N acetylglucosamine sulfatase rhGNS intrathecally into the spinal fluid to effectively treat the underlying causes of the neurologic symptoms that dominate MPS III pathology Phase I development met or exceeded all milestones In this Phase II proposal we will perform in vivo proof of principle studies using a novel MPS III mouse model and perform process development for scalable production and purification of rhGNS for preclinical and clinical development Following successful completion of this phase II proposal our therapy will be ready for pre IND studies PUBLIC HEALTH RELEVANCE Our project aims to develop a new enzyme replacement treatment for a fatal neurodegenerative disorder of childhood While rare the condition called Sanfilippo syndrome MPS IIID causes substantial disability and death as well as a large economic emotional and social burden to affected families Developing the first treatment for this disease would help to alleviate the suffering of these patients and their families and decrease long term healthcare costs The ultimate financial return on investment should be seen as the rare pediatric disease priority review voucher program which have to date sold for between $ M and $ M