New Targeted Gene Therapy for Treatment of LAMA2-Related Muscular Dystrophy

TY - PAT

T1 - New Targeted Gene Therapy for Treatment of LAMA2-Related Muscular Dystrophy

AU - Yurchenco, Peter

PY - 2019/3

Y1 - 2019/3

N2 - (A) Schematic representation of how the chimeric peptide (αLNNd) replaces the missing subunit to enable laminin polymerization. (B) Staining of polymerized chimeric protein in a mouse model of LAMA2-MD. The construct was injected intra-muscularly via an AAV vector. Invention Summary: Laminins with alpha2 subunit are major basement membrane (BM) glycoproteins of skeletal myofibers. Null mutations in the gene encoding the laminin-alpha2 subunit ( LAMA2 ) prevents laminin polymerization, which in turn disrupts the BM architecture. The result is rare form of muscular dystrophy known as LAMA2-related muscular dystrophy (LAMA2-MD). This disorder commonly presents at birth and is characterized by muscle wasting, limited motor functions, and other peripheral nerve and brain abnormalities. It has been challenging to study and develop therapeutics for LAMA2-MD since it is a rare and fatal disorder. At present there is no cure for LAMA2-MD. Patients can only rely on management of their symptoms, such as with physical therapy, speech therapy or supplemental feeding. However, gene-replacement therapy poses a promising treatment for superior mitigation of LAMA2-MD pathology. Rutgers scientists have engineered a chimeric LAMA2 protein that has been verified in a mouse model of LAMA2-MD. Muscle-specific expression of this peptide significantly ameliorated symptoms of LAMA2-MD. The construct encoding this chimeric protein can be easily packaged into an efficient vector system for targeted delivery in patients. The peptide can also be used to treat more severe forms of muscular dystrophy if used in combination with other gene therapeutics, such as a receptor binding enhancer. Additionally, the insert can be easily modified to target other laminin deficiencies. For example, replacement of the alpha-1 subunit to the beta-1 subunit could be used to potentially ameliorate Pierson syndrome, which is caused by LAMB2 mutations. Market Application: Gene therapy for muscular dystrophy Combination therapy for severe muscular dystrophy In vivo studies of laminin polymerization and related disorders Advantages: Easy packaging into AAV vector Site-specific, targeted gene-replacement Efficient expression Intellectual Property & Development Status: Patent pending. Available for licensing and/or research collaboration.

AB - (A) Schematic representation of how the chimeric peptide (αLNNd) replaces the missing subunit to enable laminin polymerization. (B) Staining of polymerized chimeric protein in a mouse model of LAMA2-MD. The construct was injected intra-muscularly via an AAV vector. Invention Summary: Laminins with alpha2 subunit are major basement membrane (BM) glycoproteins of skeletal myofibers. Null mutations in the gene encoding the laminin-alpha2 subunit ( LAMA2 ) prevents laminin polymerization, which in turn disrupts the BM architecture. The result is rare form of muscular dystrophy known as LAMA2-related muscular dystrophy (LAMA2-MD). This disorder commonly presents at birth and is characterized by muscle wasting, limited motor functions, and other peripheral nerve and brain abnormalities. It has been challenging to study and develop therapeutics for LAMA2-MD since it is a rare and fatal disorder. At present there is no cure for LAMA2-MD. Patients can only rely on management of their symptoms, such as with physical therapy, speech therapy or supplemental feeding. However, gene-replacement therapy poses a promising treatment for superior mitigation of LAMA2-MD pathology. Rutgers scientists have engineered a chimeric LAMA2 protein that has been verified in a mouse model of LAMA2-MD. Muscle-specific expression of this peptide significantly ameliorated symptoms of LAMA2-MD. The construct encoding this chimeric protein can be easily packaged into an efficient vector system for targeted delivery in patients. The peptide can also be used to treat more severe forms of muscular dystrophy if used in combination with other gene therapeutics, such as a receptor binding enhancer. Additionally, the insert can be easily modified to target other laminin deficiencies. For example, replacement of the alpha-1 subunit to the beta-1 subunit could be used to potentially ameliorate Pierson syndrome, which is caused by LAMB2 mutations. Market Application: Gene therapy for muscular dystrophy Combination therapy for severe muscular dystrophy In vivo studies of laminin polymerization and related disorders Advantages: Easy packaging into AAV vector Site-specific, targeted gene-replacement Efficient expression Intellectual Property & Development Status: Patent pending. Available for licensing and/or research collaboration.

M3 - innovation

ER -