New Drug for Muscular Dystrophy
A new drug, tested on mice and now being cautiously tested on humans, shows promise for treating a form of muscular dystrophy and other inherited diseases.
The prototype takes a revolutionary approach at tackling these rare but often crippling disorders by sidestepping genetic flaws that hamper production of a vital protein.
It has been successfully used on lab mice to restore dystrophin, a protein which maintains muscle fibres and is the key player in a tragic wasting disease called Duchenne muscular dystrophy (DMD), a study said published on Sunday.
Mice genetically engineered to have flawed DNA resulting in DMD had their muscle function restored within just two to eight weeks of being given the drug, it said.
Backed by fast-track authorization from the US drug watchdog, the researchers are now testing the drug, PTC124, on a small group of DMD patients and on others with cystic fibrosis.
DMD is one of nine forms of muscular dystrophy, a disease in which voluntary muscles become catastrophically weak.
A big subset of DMD cases is caused by so-called nonsense mutations.
These are flaws in DNA that are handed onto RNA, a molecule that is copied from DNA to provide the chemical code for making proteins.
After being duplicated from DNA, RNA goes to a cellular machine called a ribosome, which reads its code as a precursor for making the protein.
But RNA with nonsense mutations sends a premature "stop" message to the ribosome, resulting in a protein that is truncated. As a result, in the case of DMD patients with nonsense mutations, the
muscles fail to get dystrophin to replenish themselves.
PTC124 bypasses these erroneous "stop" signals, enabling the ribosome to crank out a full and functional protein.
The researchers are led by Stuart Peltz, head of a New Jersey biopharmaceutical company called PTC Therapeutics, Inc. Their paper was published online on Sunday by Nature, the British science
journal.
The team screened 800,000 compounds in a quest for a drug to bypass the coding defect, PTC Therapeutics said in a press release.
PTC124 is an oral drug that can be taken simply, the company said. In addition, it does not have the potential hazards of experimental gene-changing drugs or the burden of enzyme-replacement
therapy, which is taken periodically as an intravenous or muscular injection.
Around 1,800 inherited disorders have already been identified where nonsense mutations account for a large percentage of cases, although the genes that they affect are different, PTC Therapeutics
said
