Gene therapy for treating mucopolysaccharidosis type i

Abstract

A suspension useful for AAV9-mediated intrathecal/intracisternal and/or systemic delivery of an expression cassette containing a hIDUA gene is provided herein. Also provided are methods and kits containing these vectors and compositions useful for treating MPSI and the symptoms associated with Hurler, Hurler-Scheie and Scheie syndromes.

1 . A pharmaceutical composition suitable for intrathecal administration in human subjects, comprising a suspension of replication deficient recombinant adeno-associated virus (rAAV) in a formulation buffer, wherein:
 (a) the rAAV comprises a heterologous nucleic acid encoding human α-L-iduronidase (hIDUA), wherein said nucleic acid is operably linked to a CB7 promoter and packaged in an AAV9 capsid;   (b) the formulation buffer comprises a physiologically compatible aqueous buffer, a surfactant and optional excipients; and   (c) (i) the rAAV Genome Copy (GC) titer is at least 1×10 9  GC/mL (+/−20%);   (ii) the rAAV Empty/Full particle ratio is at least about 80% free of empty capsids; and/or   (iii) a dose of at least about 4×10 8  GC/μg brain mass to about 4×10 11  GC/μg brain mass of the rAAV suspension has potency.