– Preclinical data provide proof of concept for M002 to restore cellular uptake and lysosomal delivery and attenuate phenotype in mouse models of mucolipidosis type II –
ST. Louis Mo - May 11, 2021
- In a mouse model of MLII, mice lacking the GNPTAB gene, which encodes the a/b subunits of GlcNAc-1 phosphotransferase (PTase), were treated with M002, an AAV-9-mediated gene therapy which delivers a truncated PTase (S1S3)
- Preliminary data from MLII mice treated with M002 showed:
- Expressed S1S3 in a number of tissues including heart, liver, and salivary gland
- Increased enzyme binding to the cation-independent mannose 6-phosphate receptor (CI-MPR)
- Restored PTase activity with restored phosphorylation of a number of lysosomal enzymes
- Partially decreased levels of lysosomal enzymes secreted in serum, with concurrent increased intracellular levels in tissues including liver, heart, brain, and salivary gland
- Improved the phenotype of secretory lesions of exocrine glands, measured in the pancreas and salivary glands, which is associated with loss of PTase
- Improved sensorimotor activity
About Mucolipidosis II
Mucolipidosis II or MLII (also known as I-cell disease) is a progressively debilitating, ultra-rare autosomal recessive disorder caused by mutations in the GNPTAB gene. The mutation leads to GlcNAc-1-phosphotransferase deficiency and inability to phosphorylate (add mannose 6-phosphate, or M6P) lysosomal enzymes. As a result, lysosomal enzymes are not trafficked to lysosomes where they are needed to breakdown large molecules into smaller ones to be reused by the cell; consequently, the enzymes remain in cytoplasm or leak out to serum. Most affected individuals do not survive past early childhood. Although its exact prevalence is unknown, it is estimated to occur in about 1 in 100,000 to 400,000 individuals worldwide. MLII is apparent at birth, and slowly progressive until death in childhood. MLII is characterized by growth delays, skeletal abnormalities, facial dysmorphism, stiff skin, developmental delay, cardiomegaly, and respiratory insufficiency.
About M6P Therapeutics
M6P Therapeutics is a privately held, venture-backed biotechnology company developing the next-generation of targeted enzyme replacement and gene therapies for lysosomal storage disorders (LSDs). M6P Therapeutics’ proprietary S1S3 co-expression platform has the unique ability to enhance phosphorylation of lysosomal enzymes for both enzyme replacement and gene therapies, leading to improved biodistribution and cellular uptake of recombinant proteins and efficient cross-correction of gene therapy product. This can potentially lead to more efficacious treatments with lower therapy burden, as well as new therapies for currently untreated diseases. M6P Therapeutics’ team, proven in rare diseases drug development and commercialization, is dedicated to fulfilling the promise of enzyme replacement and gene therapies by harnessing the power of protein phosphorylation using its S1S3 co-expression platform. M6P Therapeutics’ mission is to translate advanced science into best-in-class therapies that address unmet needs within the LSD community. For more information, please visit: www.m6ptherapeutics.com.