Located within the beautiful Truckee Meadows in the Reno-Tahoe area, Strykagen is a biopharmaceutical company devoted to the development of transforming therapeutics and diagnostics for life-threatening rare muscle diseases. There is currently an unmet medical need for new therapies for the muscular dystrophies many of which have no cure and limited treatment options.

We are currently working on developing therapeutics for Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), Merosin deficient congenital muscular dystrophy (MDC1A) and Limb Girdle Muscular Dystrophies (LGMD).

Strykagen has exclusive licenses for worldwide patent pending technologies that stabilize the myomatrix and prevent muscle disease progression. These include biologic and small molecule therapeutics that target disease modifiers which have been shown to prevent muscle disease progression. We are also developing non-invasive tests to assist in the diagnosis and prognosis of muscular dystrophy.

Duchenne Muscular Dystrophy (DMD): DMD is one of the most common forms of muscular dystrophy affecting 1 in 3,500 male births. DMD patients and mdx mice (the mouse model for DMD) have mutations in the gene encoding dystrophin located on the X-chromosome. These mutations result in the absence of functional dystrophin, a 427 kDa cytoskeletal protein located under the sarcolemma of muscle fibers. In DMD patients, the compromised dystrophin linkage system causes muscle fibers to detach from the extracellular matrix during muscle contraction leading to progressive loss of muscle integrity and function. DMD patients suffer from severe, progressive muscle degeneration with clinical symptoms first detected from 2 to 5 years of age. As the disease progresses patients are confined to a wheelchair in their teens and die in their second or third decade of life from cardiopulmonary failure. There are currently no definitive therapies for DMD and the only available treatments are the steroids and palliative care.

Becker Muscular Dystrophy (BMD): BMD is a dystrophinopathy caused by mutations in the dystrophin gene that result in a truncated, partially functional dystrophin protein. The truncated dystrophin protein results in sarcolemmal instability and progressive muscle disease. BMD is less common than DMD and occurs in between 3-6/100,000 male births. BMD patient’s exhibit symptoms between 8-15 years of age and can exhibit dilated cardiomyopathy and reduced life expectancy. There are currently no definitive therapies for BMD and only steroid therapy and palliative care are available.

Merosin Deficient Congenital Muscular Dystrophy Type 1A (MDC1A): MDC1A is a common form of congenital muscular dystrophy with an incidence estimated at 0.89/100,000. MDC1A is caused by mutations in the LAMA2 gene located on human chromosome 6q22-23 resulting in loss or a truncated form of laminin-α2 protein. Loss of laminin-α2 protein in MDC1A results in the absence of laminin-211/221 (merosin), the major component of the basal lamina, that surrounds skeletal and cardiac muscle. MDC1A patients exhibit severe muscle weakness from birth (“floppy baby” syndrome), dysmyelinating neuropathy, muscle atrophy and limited eye movement. Patients exhibit feeding problems and/or respiratory difficulties and often require the placement of a feeding tube and/or ventilator assistance. Most MDC1A patients are unable to walk without assistance and are confined to a wheelchair. MDC1A patients exhibit changes in brain white matter that is observed after 6 months of age and associated with increased likelihood of seizures. There is currently no cure or effective treatment for MDC1A and patients can die as early as the first decade of life.

Limb Girdle Muscular Dystrophy 2I (LGMD2I): Is an autosomal recessive congenital muscular dystrophy caused by mutations in the gene encoding Fukutin Related Protein (FKRP) located on chromosome 19q13.2. FKRP protein is required for the glycosylation of α-dystroglycan (a component of the dystrophin associated protein complex), which is needed for binding to laminin-211/221 in the muscle basal lamina. In the brain glycosylated α-dystroglycan is required for neuronal migration during development. MDC1C is an allelic version of the disease caused by mutations on FKRP that result in muscle weakness, brain abnormalities and intellectual disability. LGMD2I patients exhibit progressive weakness in the limbs and shoulders that affect ability to walk and some patients exhibit cardiomyopathy. There is currently no cure or effective treatment or LGMD2I or MDCIC.

Targeting an increase in the α7β1 integrin laminin receptor in skeletal muscle may act to compensate for the lost laminin adhesion and reduce muscle disease progression in LGMD2I.

Integrin therapeutics for the treatment of muscular dystrophy

The α7β1 integrin is the predominant laminin-binding integrin in cardiac and skeletal muscle. Several studies have demonstrated the α7β1 integrin is a major modifier of disease progression in DMD and MDC1A.

  • Enhanced transgenic expression of the α7 integrin in the skeletal muscle of mouse models of DMD and MDC1A improves muscle pathology and increases life expectancy.
  • Loss of α7 integrin in the dystrophin deficient mdx mouse model of DMD accelerates muscle disease progression.
  • AAV-mediated gene transfer of α7 or β1D integrin alleviates muscle disease in mouse models of DMD.
  • Together these results support the idea the α7β1 integrin is target for drug-based therapies.

Strykagen has licensed worldwide patent pending technology from the University of Nevada, Reno for several novel integrin enhancing therapeutics for the treatment of muscular dystrophy.

Strykagen Corp is located at the University Nevada School of Medicine. This laboratory space is fully equipped for modern molecular and cell biology for the development of therapies, diagnostics and biomarkers for the muscular dystrophies.