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 4 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-6-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.
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 $67.5M and $350M.
| Ekins, Sean; Perlstein, Ethan O (2018) Doing it All - How Families are Reshaping Rare Disease Research. Pharm Res 35:192 |
| Ekins, Sean (2017) Industrializing rare disease therapy discovery and development. Nat Biotechnol 35:117-118 |
| Ekins, Sean; Wood, Jill (2016) Incentives for Starting Small Companies Focused on Rare and Neglected Diseases. Pharm Res 33:809-15 |
