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New Gene Therapies for Neuromuscular Disease

Giving kids strength through precision medicine – new gene therapies for neuromuscular disease.

Cook Children's Clinical Care Center designation from the Muscular Dystrophy Association reaffirms our commitment to excellence in clinical care for our patients with neuromuscular disorders, and represents the continuum of a more than 30-year relationship. This designation by MDA comes at a most exciting time in the treatment of children with neuromuscular disorders. Warren Marks, M.D., leads our multidisciplinary team, joined by new physician Stephanie Acord, M.D., and Marcie Baldwin, PNP (clinic coordinator). We are joined by specialists and support staff from a wide range of disciplines to provide comprehensive care to children with neuromuscular disorders. Consultations are available by contacting the Jane and John Justin Neurosciences Center at Cook Children's at 682-885-2500.

In the past few months, new treatments have received FDA approval for two of the most devastating forms of childhood neuromuscular disorders – spinal muscular atrophy (SMA) and Duchenne muscular dystrophy (DMD).

Spinal muscular atrophy (SMA):

SMA is a genetic neuromuscular disease characterized by degeneration of motor neurons in the spinal cord resulting in progressive weakness. SMA affects 8-10 per 1,000 babies born in the United States, and is among the leading genetic causes of infant death.

Most SMA is caused by a lack of the SMN-1 protein located on chromosome 5. A secondary, truncated protein, SMN-2 can offer some protection. The age of onset and degree of severity of disease correlates with the amount of SMN-2.
SMA is classified based on age of presentation and degree of motor skill attainment.

  • Type 1 (Werdnig-Hoffman disease) presents in infancy with hypotonia and weakness. Infants are unable to sit, roll, crawl or stand. Untreated, most infants will not survive beyond 2 years of age. These children usually have 1-2 copies of SMN-2.
  • Type 2 (Dubowitz disease) presents later in infancy (7-18 months). Infants are typically able to sit, but not stand or walk, and have longer survival with 70 percent alive at age 25 years.
  • Type 3 (Kugelberg Welander disease) develop symptoms at 18 months. They often develop and then later lose the ability to walk. Life expectancy may be normal.
  • Type 4 presents in adulthood with progressive weakness. They usually retain the ability to walk and life expectancy can be normal.

While there is presently no cure, treatment is now available.

Recently, the FDA approved a drug called Nusinersen (SPINRAZA™ – Biogen pharmaceuticals) which increases the production of SMN-2, thus potentially decreasing disease severity. It is administered via intrathecal injection. Patients receive six doses during the first year and three doses annually for ongoing treatment.

Early treatment offers the best chance of successful treatment. As with most new gene based therapies, the treatment is expensive and not yet covered by most insurance companies, making this treatment an option only in exceptional cases presently.

Thanks to a dedicated team of professionals, Cook Children's was the first hospital in North Texas to administer this treatment since FDA approval in December 2016 and hopes to continue working with the manufacturer and insurance companies to make this treatment readily available to more kids in need.

Duchenne muscular dystrophy

Duchenne muscular dystrophy, the most recognizable and severe form of childhood muscular dystrophy affects boys in early infancy with delayed walking (usually beyond 18 months) amongst other delays. The large, firm calves are apparent on physical examination and elevation of the muscle enzyme creatine kinase (CK) is characteristic. Elevations of “liver” enzymes may be another early laboratory marker, but this is because these enzymes are also produced in muscle. Genetic confirmation of an alteration of the dystrophin gene is used for confirmation and treatment planning.

Dystrophin is a structural membrane protein encoded by the dystrophin gene. This very large gene has 79 exons which encode different portions which are then assembled into the final dystrophin protein. This gives rise to many opportunities for errors. While absence of dystrophin produces Duchenne muscular dystrophy; partial production results in the related but milder Becker variant.

Targeted gene therapy is now available to skip exon 51, a common region of error resulting in Duchenne muscular dystrophy. This exon skipping medication, known as eteplirsen (Saretpa pharmaceuticals) allows the body to produce a shortened, but partially effective dystrophin protein by skipping over the region of the gene which is mutated and offers disease slowing treatment to about 15 percent of affected boys. Other exon skipping medications are currently under development and this technology may soon be applicable to other neurological conditions. The medication requires weekly intravenous infusion. Cook Children’s currently has seven boys on or preparing to start therapy.

Muscular Dystrophy Association Clinic