Muscular dystrophy (MD) comprises a group of diseases that are clinically manifested as progressive muscle weakness with associated loss of mobility, agility, and body movements due to defects in genes for the production of muscle proteins. Devastating to patients, families, and caregivers, and clinically known for over 150 years, there is as yet no cure for MD.

Despite the challenges to finding a cure, however, the proteins and structures involved in certain disease processes are increasingly being elucidated, raising the number of potential pharmaceutical targets, and resulting in heightened interest in investment, partnership, and collaboration. In addition, several companies pursing potential treatments for MD have advanced to the Phase II and III stages of clinical drug development, and one product may be fully approved in the near future.

There are at least nine major types of MD: Duchenne (DMD), Becker (BMD), congenital, distal, Emery-Dreifuss, facioscapulohumeral (FSHD or FSH), limb-girdle, myotonic dystrophy, and oculopharyngeal. Most of the pharmaceutical and regulatory efforts to date have focused on DMD, because it is the most severe and because of considerable scientific advances regarding its pathology, and BMD, because its disease mechanism is related to DMD.

MD can be inherited in three ways: (1) autosomal inheritance (from a normal gene from one parent and an abnormal gene from another parent), (2) autosomal recessive inheritance (both parents carry and pass on the faulty gene), and (3) X-linked recessive inheritance (when a mother carries the affected gene and passes it on to her son). Sporadic cases may also arise as a result of de novo mutation, in the absence of any family history of affected individuals. The distribution of weakness in MDs includes a limb-girdle pattern, with shoulder and hip girdle muscle involvement; a humeroperoneal pattern, with predominantly triceps, biceps, and peroneal muscles weakness; or a distal pattern, with distal weakness in the legs and arms. The prevalence of MD ranges from 1.3 to 96.2 per million, with DMD being most prevalent among boys during childhood, and myotonic dystrophy as one of the more common forms of MDs worldwide. Traditionally, the classification of MD is based on a combination of clinical and pathological criteria, including age of onset and distribution of muscle weakness, the extent of disease progression, associated symptoms, systemic features, family history, serum creatine kinase, muscle histology, as well as electromyography and nerve conduction studies (EMG/NCS). Increasingly, diagnosis requires genetic confirmation, as there can be considerable variations and overlaps in the clinical phenotypes.

FSHD is a complex, inheritable muscle disease. Although frequently cited as the third most common type of MD in older reports, many newer sources rank FSHD as the most prevalent type of MD, occurring at a rate of some 7 cases/1,000 persons, as compared with DMD/BMD (5 cases/1,000) and myotonic dystrophy (4.5 cases/1,000). The identification of FSHD as the most common type of MD has important ramifications, for example, when allocating future Federal (U.S.) funding for research, and in terms of the potential market size for future FSHD treatments. FSHD has only recently attracted attention from the pharmaceutical industry, largely due to significant advances in the understanding of the gene/mechanism of disease, including over-expression of a protein called DUX4. Most individuals with FSHD inherit the mutation from a parent with the disease, with 10–33% of all FSHD cases resulting from a de novo (or sporadic) mutation. The major symptom of FSHD is progressive weakening and loss of skeletal muscles. The usual location of these weaknesses at onset is the origin of the name: face (facio), shoulder girdle (scapulo), and upper arms (humeral). There is currently no disease modifying treatment or cure for FSHD. Most treatments proposed to “treat” FSHD have not yet been tested in randomized clinical trials. These may include: hormone supplementation, protein supplements (creatinine monohydrate), or drugs used to decrease inflammation (e.g., prednisone). To better understand and validate their use, many are now being properly investigated in clinical trials.