ShareThisWriters don't like to admit it, but everyone needs a little editing now and then.
The same thing is true for our genetic code. A few jumbled letters can mix up or silence critical instructions that make a biological system work.
Much of today's medical research is geared toward finding ways to either fix or bypass such coding mistakes.
And one of the more dramatic advances for this strategy was reported this week in the Annals of Neurology by muscular dystrophy researchers in the United States and Japan.
They used a mixture of lab-made compounds that serve as molecular patches to bypass mutant DNA segments, called exons, on a gene that carries instructions for a muscle protein, dystrophin. The exon-skipping molecules produced positive results in dogs afflicted with a canine version of Duchene muscular dystrophy.
Other teams of scientists have already done preliminary studies on humans using similar compounds and are preparing for another round of trials.
Duchene muscular dystrophy (DMD) is the most severe form of childhood onset diseases that weaken movement muscles in the body. The genetic disease affects boys almost exclusively, affecting 1 in 3,500 and gradually weakens voluntary skeletal muscles, including the diaphragm and other breathing muscles and the heart.
Symptoms begin at about 3 years of age and most boys with the condition lose the ability to walk by age 12. Few boys with the disease survive beyond their 20s, succumbing to heart or respiratory failure.
The canine version of the disease occurs naturally in dogs and affects the same gene that's mutated in humans.
Investigators led by Toshifumi Yokota and Eric Hoffman of the Children's National Medical Center in Washington and Shin'ichi Takeda of Japan's National Center of Neurology and Psychiatry in Tokyo, showed that the DNA patches allowed three test dogs to produce an imperfect, but functional, version of dystrophin that significantly improved muscle performance, including the ability to run faster, in the treated dogs compared to control animals.
However, the treatment did not affect deterioration of muscles in the dogs' hearts. The researchers note that the muscles of the heart are less porous than skeletal muscles, and thus may not have absorbed enough of the compound to correct the genetic defect in that organ.
But knowing that the treatment works on other muscles makes it worthwhile to explore better means of delivering the genetic patches to the heart.
And proving that the therapy can effectively bypass defects on more than one section of the large gene that makes the muscle protein suggests that the strategy could help at least 80 percent to 90 percent of patients with DMD.
Patching over mistakes in the gene for dystrophin is particularly challenging because it's huge. While the average human gene contains about 3,000 chemical letters of coding information, the dystrophin gene carries 2.4 million of those letters.
"This trial makes the much-talked about promise of exon-skipping as a systemic treatment for DMD in humans a real possibility in the near term," said Yokota, although the researchers note that the artificial DNA patches must be delivered in large amounts and that the technology to make them is, so far, slow and costly.
Earlier studies have showed that it was possible to inject DNA patches into the bloodstream of mice and deliver them throughout their bodies. The new report demonstrates the technique works for larger animals.
A British study reported in January involved 10 boys between the ages of 12 and 17 who were injected with a single patch compound just one time in a foot muscle, with a saline solution injected into the other foot. All of the boys tolerated the injections well and there was evidence of increased dystrophin production in the treated foot for each one.
A December report from a Dutch firm said four boys with DMD between the ages of 10 and 13 began producing muscle-moving protein after getting injections of yet another exon-skipping compound in leg muscles.
Another group of researchers, working for a New Jersey pharmaceutical company, has been working with a drug that's designed to tell muscle fibers to ignore faulty genetic instructions and continue making the dystrophin protein.
They've done one round of tests on 38 boys and found that muscle cells seemed to respond to the drug in all of them after taking it for 28 days. Another test with a larger group will administer the drug for up to a year and look for evidence that it preserves or even improves muscle strength and function over time.
On the Net: http:/www.mda.org
www.childrensnational.org
(Reach Lee Bowman at bowmanl(at)shns.com.)
The Medical Journal
