Gene therapy for X-linked Emery-Dreifuss muscular dystrophy

This technology is a gene therapy approach that restores expression of human emerin protein in cardiac and skeletal muscles.

Unmet Need: Disease-modifying therapy for X-linked Emery-Dreifuss muscular dystrophy

Emery-Dreifuss muscular dystrophy (EDMD) is a rare muscular disorder causing joint degradation, muscle wasting, and life-threatening heart disease. The most common subtype of EDMD is driven by mutations in the X-linked EMD gene, leading to loss of the protein emerin. Current treatment options are limited to supportive and symptomatic care, with no disease-modifying therapies available.

The Technology: Non-toxic gene therapy for treating disorders caused by emerin deficiency

This technology uses Adeno-associated virus (AAV) to selectively deliver functional human emerin protein to striated muscles. By utilizing a promoter that drives expression specifically in muscle, this approach restores strong expression of emerin in heart and skeletal muscles without inducing significant toxicity to the liver or kidney.

This technology has been validated with mice lacking a functional copy of the EMD gene and a human iPSC-derived cardiomyocyte model of X-linked EDMD.

Applications:

• Gene therapy for X-linked EDMD and related disorders caused by emerin deficiency

• Treatment of emerin-related cardiomyopathy

• Research tool for studying X-linked EDMD

• Platform for developing gene therapies for other striated muscle diseases

• Platform for developing non-AAV delivery platforms

Advantages:

• Disease-modifying approach

• Restores robust and specific emerin expression

• Restores proper localization of emerin protein

• Minimizes off-target and systemic toxicities

• Support long-term therapeutic efficacy and safety

Lead Inventor:

Howard J. Worman, M.D.

Related Publications:

• Herrada I, Samson C, Velours C, Renault L, Ostlund C, Chervy P, Puchkov D, Worman HJ, Buendia B, Zinn-Justin S. “Muscular dystrophy mutations impair the nuclear envelope emerin self-assembly properties” ACS Chem Biol. 2015 Dec; 10(12): 171-176.

• Wolff N, Gilquin B, Courchay K, Callebaut I, Worman HJ, Zinn-Justin S. “Structural analysis of emerin, an inner nuclear membrane protein mutated in X-linked Emery-Dreifuss muscular dystrophy” FEBS Lett. 2001 Jul; 501(2-3): 171-176.

• Ostlund C, Ellenberg E, Hallberg E, Lippincott-Schwartz J, Worman HJ. “Intracellular trafficking of emerin, the Emery-Dreifuss muscular dystrophy protein” J Cell Sci. 1999 Jun; 112(11): 1709-1719.

Tech Ventures Reference:

• IR CU26383, CU26392

• Licensing Contact: Jerry Kokoshka