Methods and compositions for CNS delivery of iduronate-2-sulfatase
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 iduronate-2-sulfatase (I2S) protein, salt, and a polysorbate surfactant for the treatment of Hunters Syndrome.
1. A stable formulation for CNS delivery comprising a recombinant iduronate-2-sulfatase (I2S) protein at a concentration of at least 5 mg/ml, a polysorbate surfactant at a concentration of approximately 0.001-0.5%, and no greater than 5 mM phosphate.
2. The formulation of claim 1 , wherein the I2S protein is present at a concentration of at least about 10 mg/ml.
3. The formulation of claim 1 , wherein the I2S protein is present at a concentration of 10 mg/ml.
4. The formulation of claim 1 , wherein the 12S protein comprises an amino acid sequence of SEQ ID NO:1.
5. The formulation of claim 1 , wherein the formulation further comprises salt.
6. The formulation of claim 5 , wherein the salt is NaCl.
7. The formulation of claim 1 , wherein the polysorbate surfactant is polysorbate 20.
8. The formulation of claim 7 , wherein the polysorbate 20 is present at a concentration of approximately 0.005-0.02%.
9. The formulation of claim 1 , wherein the formulation has a pH of approximately 5.5-7.0.
10. The formulation of claim 1 , wherein the formulation is a liquid formulation.
11. The formulation of claim 1 , wherein the formulation is formulated as lyophilized dry powder.
12. The formulation of claim 1 , wherein 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.
13. The formulation of claim 1 , wherein the formulation is administered in a volume of about 1-15 ml.
14. The formulation of claim 1 , wherein the CNS delivery is by intrathecal administration.
15. The formulation of claim 1 , wherein the CNS delivery is by intracerebroventricular (ICV) administration.