Duchenne muscular dystrophy (DMD) is a form of muscular dystrophy that
is characterized by decreasing muscle mass and progressive loss of
muscle function, which occurs as a consequence of the absence of the
dystrophin protein. It affects about 1 in 5,000 people and usually
results in death before the age of thirty. We recently discussed how the
mdx mouse model of DMD has contributed to the development of potential
treatments for the disease.
While such treatments are potentially very valuable their disadvantage
is that they can only help a minority of DMD patients who have a
particular defects in the dystrophin gene.
In recent years scientists researching treatments that would benefit all
DMD patients have attempted to use stem cells to replace the muscle
cells that are defective in mouse models of DMD, but until now the
results have been disappointing, with little sign of improved muscle
function. Furthermore there have been concerns that embryonic stem (ES)
cells injected into mice can develop into tumours (1,2).
In a study (3) published in Nature Medicine this week Rita Perlingeiro
and colleagues at University of Texas Southwestern found that by
inducing the expression of Pax 3, a transcription factor which is
thought to kick start muscle development, they were able to coax ES
cells to differentiate into muscle cells. Furthermore by selecting ES
derived muscle cells that expressed the marker protein PDGF-alpha, but
not the marker Flk-1, they identified those that when injected into mdx
mice grafted onto their muscles and significantly improved muscle
strength and coordination. Better still there was no sign of any tumour
By identifying several requirements for stem cells to develop into
muscle cells that can be safely used to replace those lost in DMD Dr.
Perlingeiro and colleagues have taken an important step towards
developing a stem cell treatment for human use.
1) Fujikawa, T. et al. " Teratoma formation leads to failure of
treatment for type I diabetes using embryonic stem cell–derived
insulin-producing cells." Am. J. Pathol. 166, 1781–1791 (2005). PubMed:
2) Roy N.S. et al. "Functional engraftment of human ES cell-derived
dopaminergic neurons enriched by coculture with telomerase-immortalized
midbrain astrocytes." Nat Med. 12(11):1259-68 (2006).PubMed: 17057709
3) Darabi R et al. "Functional skeletal muscle regeneration from
differentiating embryonic stem cells" Nat Med. Advanced publication
online: 20 January 2008.