Gene therapy for treating mucopolysaccharidosis type i
AssigneeThe Trustees of the University of Pennsylvania
InventorsChristian Hinderer, James M. Wilson
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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.
Claims26
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 1×109 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 4×108 GC/g brain mass to about 4×1011 GC/g brain mass of the rAAV suspension has potency.
A method of treating a human patient having MPS I and/or the symptoms associated Hunter syndrome, the method comprising:
- (a) dosing a patient having MPS I and/or the symptoms associated with Hunter syndrome with a sufficient amount of hIDUA enzyme to induce transgene-specific tolerance;
- and
- (b) administering an rAAV.hIDUA to the patient, which rAAV.hIDUA directs expression of therapeutic levels of hIDUA in the patient.
Dependencies are inferred from the claim text.