Methods and compositions for cns delivery of arylsulfatase a

Abstract

Provided are methods of treating metachromatic leukodystrophy comprising administering to a subject in need of treatment a therapeutically effective amount of recombinant arylsulfatase A enzyme.

1 - 75 . (canceled) 
     
     
         76 . A method of treating metachromatic leukodystrophy (MLD) Syndrome comprising a step of
 administering intrathecally to a subject in need of treatment a recombinant arylsulfatase A (ASA) enzyme at a therapeutically effective dose and an administration interval for a treatment period sufficient to improve, stabilize or reduce decline of one or more motor functions relative to baseline.   
     
     
         77 . The method of  claim 76 , wherein the administering of the recombinant ASA enzyme further results in improvement, stabilization or reduction decline of one or more cognitive, adaptive, and/or executive functions. 
     
     
         78 . The method of  claim 76 , wherein the one or more motor functions comprise gross motor function. 
     
     
         79 . The method of  claim 78 , wherein the gross motor function is assessed by a Gross Motor Function Measure (GMFM) test. 
     
     
         80 . The method of  claim 79 , wherein the GMFM test is GMFM-88 and administering the recombinant ASA enzyme results in decline of the GMFM-88 score by less than 10%, 20%, 30%, 40%, or 50%. 
     
     
         81 . The method of  claim 76 , wherein the therapeutically effective dose is greater than 30 mg. 
     
     
         82 . The method of  claim 76 , wherein the therapeutically effective dose is greater than 100 mg. 
     
     
         83 . The method of  claim 76 , wherein the therapeutically effective dose is less than 200 mg. 
     
     
         84 . The method of  claim 76 , wherein the administration interval is at least once a week, at least every other week or at least monthly. 
     
     
         85 . The method of  claim 76  comprising a step of administering intrathecally to a subject in need of treatment a recombinant arylsulfatase A (ASA) enzyme at a therapeutically effective dose and an administration interval for a treatment period sufficient to increase levels of a biomarker that is decreased in MLD in a brain tissue relative to a baseline level of the biomarker. 
     
     
         86 . The method of  claim 85 , wherein the biomarker is N-acetylaspartate. 
     
     
         87 . The method of  claim 86 , wherein levels of N-acetylaspartate are assessed by proton magnetic resonance spectroscopy. 
     
     
         88 . A method of treating metachromatic leukodystrophy (MLD) Syndrome comprising a step of
 administering intrathecally to a subject in need of treatment a recombinant arylsulfatase A (ASA) enzyme at a therapeutically effective dose and an administration interval for a treatment period sufficient to decrease levels of a biomarker that accumulates in MLD in a bodily fluid selected from the group consisting of cerebrospinal fluid, urine, blood, and blood serum relative to a baseline level of the biomarker.   
     
     
         89 . The method of  claim 88 , wherein the biomarker is selected from the group consisting of sulfatide, lysosulfatide, and combinations thereof. 
     
     
         90 . The method of  claim 88  comprising
 administering intrathecally to a subject who is at risk of or suffering from metachromatic leukodystrophy the recombinant arylsulfatase A enzyme at a therapeutically effective dose and an administration interval for a treatment period sufficient to decrease sulfatide levels in the cerebrospinal fluid (CSF) relative to baseline. 
 
     
     
         91 . A method of treating metachromatic leukodystrophy (MLD) Syndrome comprising a step of
 administering intrathecally to a subject in need of treatment a recombinant arylsulfatase A enzyme at a therapeutically effective dose and an administration interval for a treatment period sufficient to stabilize or reduce brain lesion involvement relative to baseline.   
     
     
         92 . The method of  claim 91 , wherein brain lesion involvement is assessed by the MLD MRI (Magnetic Resonance Imaging) severity score. 
     
     
         93 . The method of  claim 92 , wherein the administering of the recombinant ASA enzyme results in stabilization of the MLD MRI severity score in the subject relative to baseline. 
     
     
         94 . The method of  claim 91 , wherein the subject is human. 
     
     
         95 . The method of  claim 91 , wherein the treatment interval is at least 6 months.