Compositions useful in treatment of metachromatic leukodystrophy
AssigneeThe Trustees of the University of Pennsylvania
InventorsJuliette Hordeaux, James M. Wilson
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Abstract
Provided is a recombinant adeno-associated virus (rAAV) having an AAVhu68 capsid and a vector genome which comprises a nucleic acid sequence encoding a functional human arylsulfatase A (ARSA). Also provided are a production system useful for producing the rAAV, a pharmaceutical composition comprising the rAAV, and a method of treating a subject having metachromatic leukodystrophy, or ameliorating symptoms of metachromatic leukodystrophy, or delaying progression of metachromatic leukodystrophy via administrating an effective amount of the rAAV to a subject in need thereof.
Claims14
A pharmaceutical composition for use in treating metachromatic leukodystrophy or a disease associated with an arylsulfatase A (ARSA) gene mutation, said pharmaceutical composition comprising
- recombinant adeno-associated virus (rAAV) comprising an AAVhu68 capsid;
- and a vector genome), comprising:
- a 5′ AAV inverted terminal repeats (ITR), a CB7 promoter comprising a CMV IE enhancer and a CB promoter, and a nucleic acid sequence encoding a functional human Arylsulfatase A (hARSA) operably linked to regulatory sequences comprising the CB7 promoter which direct the hARSA expression, a polyA signal, and a 3′ AAV ITR wherein the hARSA coding sequence comprises a sequence of nucleotide (nt) 1 to nt 1521 of SEQ ID NO:
- 1, or a sequence at least 95% identical thereto which encodes a functional hARSA;
- and
- at least one aqueous buffer, at least one carrier, at least one excipient and/or a least one preservative,
- said pharmaceutical composition being deliverable in a single therapeutic dose via intrathecal administration.
12-14. (canceled)
A method of treating Metachromatic Leukodystrophy or a disease associated with a Arylsulfatase A (ARSA) gene mutation in a subject in need thereof, the method comprising administering a single dose of a recombinant AAV to the subject by ICM injection, wherein the recombinant AAV comprises an AAVhu68 capsid and a vector genome packaged therein, said vector genome comprising AAV ITRs, an hARSA coding sequence comprising SEQ ID NO:
- 1, or a sequence at least 95% identical thereto that encodes a functional hARSA, and regulatory sequences which direct expression of the functional hARSA in a target cell, wherein the single dose is
- (i) about 3.3×1010 genome copies (GC)/gram of brain mass;
- (ii) about 1.1×1011 GC/gram of brain mass;
- or
- (iii) about 3.3×1011 GC/gram of brain mass.
Dependencies are inferred from the claim text.