Gene therapy for treating mucopolysaccharidosis type ii

Abstract

A suspension useful for AAV9-mediated intrathecal and/or systemic delivery of an expression cassette containing a hIDS gene is provided herein. Also provided are methods and kits containing these vectors and compositions useful for treating Hunter syndrome and the symptoms associated with Hunter syndrome.

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 iduronate-2-sulfatase (hIDS) packaged in an AAV9 capsid;   (b) the formulation buffer comprises a physiologically compatible aqueous buffer, and optional surfactants and excipients; and   (c) (i) the rAAV Genome Copy (GC) titer is at least 1.0×10 13  GC/ml (+/−20%); and/or
 (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 2.5×10 10  GC/g brain mass to about 3.6×10 11  GC/g brain mass of the rAAV suspension has potency.