TS-000513 — Dystrophinopathies are a group of disorders caused by mutations in the DMD gene which codes for dystrophin, the vital, muscle-specific structural protein. Currently, there is no cure for muscular dystrophy, and patients only rely on palliative care options. Our gene therapy researchers at Nationwide Children’s Hospital have developed an AAV-mediated gene editing method for correcting deleterious DMD mutations in affected patients. This therapy uses a homology-independent targeted integration (HITI) to replace any missing or aberrant exons in affected patients; therefore, correcting the underlying cause of DMD. This therapy will be developed to stop the progression of muscle wasting and fibrosis in individuals with DMD mutations that result in muscular dystrophy via permanent correct of the underlying cause within muscle tissue by replacing missing or aberrant exons using HITI. Advantages By developing AAV-Mediated HITI gene editing for correction of diverse DMD mutations in patients with muscular dystrophy, we can potentially cure BMD and DMD patients. These patients currently have no palliative care options. Our compositions of matter for this approach (i.e. genomic target region, guide-RNA sequences, donor DNA sequences) are new. Stage of Development Proof of concept studies completed Intellectual Property Provisional Patent Pending

TS-000438 — Gene therapy experts at Nationwide Children’s have developed an AAV-mediated CRISPR/Cas9 gene editing method for the correction of exon duplications in patients with DMD (Duchenne muscular dystrophy). This therapy has the potential to permanently corrects DMD by stopping and potentially reversing the progression of muscle wasting and fibrosis in affected individuals. Currently about 11% of DMD cases are caused by exon duplications and our experts plan to use this invention to correct for this underlying cause within muscle tissues.

TS-000358 — Congenital Muscular Dystrophy Type 1A (CMD1A) usually presents in the neonatal period with marked muscle weakness and severe hypotonia. CMD1A patients show deficiency in laminin-alpha2 (LAMA2) protein caused by the genetic mutations leading to weaker and unstable muscle tissue. Gene therapy experts at Nationwide Children’s Hospital have developed a gene and protein therapy approach enabling delivery of key domains of LAMA2 using adeno-associated virus (AAV). In addition, our experts have engineered fusion proteins that assist in anchoring LAMA2 to the muscle membrane thereby improving the muscle-matrix interaction and muscle integrity.

TS-000308 — Absence of the dystrophin protein leads to the severe muscle disorder Duchenne Muscular Dystrophy (DMD). Nearly asymptomatic patients have been identified to produce a functional N-terminal truncated dystrophin protein. Gene therapy experts at Nationwide Children's Hospital are developing a U7-snRNA exon skipping strategy to facilitate expression of a truncated dystrophin protein for patients carrying mutations within exon 6 to 9 of the DMD gene, rendering their dystrophin nonfunctional. Our experts have effectively skipped exon 8 in patient-derived cell lines and in turn produced a functional truncated dystrophin protein product.

TS-000199 — Facioscapulohumeral Muscular Dystrophy (FSHD) is the third most common muscular dystrophy, affecting 1 in 20,000 individuals. There is no current treatment for FSHD; therefore, animal models of the disease are essential for testing potential therapies. Researchers at Nationwide Children’s Hospital have developed a mouse model that recapitulates the FSHD phenotype and develops myopathy. This is an inducible FSHD mouse model that stably expresses the disease-causing gene, DUX4, from the mouse genome using the human DUX4 promoter. Importantly, in comparison to other FSHD mouse models, this particular inducible model circumvents lethality and leakiness problems seen in past models of the disease. Available for purchase through Jax Labs jax.org Stock No: 032779 Potential Applications/Markets: The FSHD field is lacking a good mouse model that recapitulates FSHD phenotypes and develops myopathy. Opportunity/Seeking: Licensing

TS-000178 — A novel mouse model for testing exon skipping therapies for DMD disease has been generated at Nationwide Children’s Hospital. This mouse model carries a duplicated exon (exon2) in the DMD gene as compared to a point mutation in the most common mdx mouse model. This unique dystrophic mouse can serve as a preclinical testing model to test various therapies that mediate exon skipping.

TS-000127 — Putative cytidine monophosphate-N-acetylneuraminic acid hydroxylase-like protein is an enzyme that in humans is encoded by the CMAH gene. A new CMAH-Deficient mouse model for DMD-related research has been created. The CMAH-Deficient mouse model mimics the human disease better than the current standard model thus providing a model for DMD that facilitate translational research to be more relevant to issues affecting the human disease. Available through Jax Labs: Jax.org Stock #017929 Stage of Development: Development is Complete Potential Applications/Markets: It can be used to study development of drugs and biologics to treat Duchenne Muscular Dystrophy, therefore its primary application is in translational research. Opportunity / Seeking: Licensing