Methods and compositions for CNS delivery of arylsulfatase A
The present invention provides, among other things, compositions and methods for CNS delivery of lysosomal enzymes for effective treatment of lysosomal storage diseases. In some embodiments, the present invention includes a stable formulation for direct CNS intrathecal administration comprising an arylsulfatase A (ASA) protein, salt, and a polysorbate surfactant for the treatment of Metachromatic Leukodystrophy Disease.
1. A method of treating metachromatic leukodystrophy (MLD) comprising a step of administering directly into the cerebrospinal fluid of a subject in need of treatment a formulation comprising an arylsulfatase A (ASA) protein at a concentration at or greater than 10 mg/ml at a dose amount of at least 100 mg, salt, polysorbate, wherein the formulation comprises no greater than 10 mM phosphate, and wherein the formulation has a pH of between 5.5-6.5.
2. The method of claim 1 , wherein the formulation comprises phosphate at a concentration of no greater than 5 mM.
3. The method of claim 1 , wherein the ASA protein is present at a concentration of between about 10 mg/ml and 30 mg/ml.
4. The method of claim 1 , wherein the salt is NaCl and the polysorbate is polysorbate 20, and the formulation comprises NaCl at a concentration of approximately 154 mM, polysorbate 20 at a concentration of approximately 0.005%, and a pH of approximately 6.
5. The method of claim 1 , wherein the formulation is administered in a volume of about 1-5 ml.
6. The method of claim 1 , wherein direct administration into the cerebrospinal fluid is via intraparenchymal, intracerebral, intraventricular cerebral (ICV) or intrathecal (IT) administration.