PTC THERAPEUTICS LAUNCHES
TRIAL OF DRUG FOR DUCHENNE DYSTROPHY

PTC Therapeutics (www.ptcbio.com), a biopharmaceutical company in South Plainfield, N.J., has started a phase 1 clinical trial of an experimental drug called PTC124 that’s designed to overcome the effects of a specific mutation (flaw) in the gene for the dystrophin protein in boys with Duchenne muscular dystrophy (DMD). This trial is for safety only and is being conducted in healthy volunteers.

If the results are satisfactory, the company plans to begin a phase 2 trial in patients with DMD during the first half of 2005. (PTC also plans to test the drug in cystic fibrosis, a genetic disorder that affects the lungs and pancreas, at that time.)

“We are very glad to see this project moving forward,” said Sharon Hesterlee, MDA’s director of Research Development. “PTC Therapeutics has demonstrated a real commitment to developing therapies for genetic disease and has conscientiously kept the muscular dystrophy community in the loop.”

PTC124 (see “Drug May Help DMD-Affected Cells,” Research Updates, Quest, January/February 2004) appears to influence the way cells read genetic information. It allows a cell’s reading mechanism to skip over mutations that would otherwise cause it to stop making a protein prematurely.

PTC124, which is given by mouth, specifically targets “premature stop codon” mutations, also called “nonsense” mutations. According to PTC, the drug has demonstrated the ability to restore full-length functional dystrophin protein molecules in dystrophin-deficient mice with a disease closely resembling DMD. Dystrophin is the muscle protein needed but missing in DMD.

The drug has similar actions to gentamicin, an antibiotic that also induces cells to read through faulty instructions for dystrophin, but it has a completely different chemical structure and may pose a lower risk of side effects.

H. Lee Sweeney, an MDA grantee at the University of Pennsylvania who is studying stop codon read-through in DMD, said he’s “extremely optimistic” about PTC124. “It looks like a real drug, and it looks like it’s going to work, at least in some of the kids.”

Sweeney is on MDA’s Translational Research Advisory Committee and on PTC Therapeutics’ Scientific Advisory Board.

Patients who may benefit from this type of drug are those with DMD who have premature stop codons in the dystrophin gene. It’s been estimated that this group constitutes about 15 percent of the DMD population.

Determining the nature of a dystrophin mutation requires specialized testing available at the University of Utah, PTC Therapeutics advises. (See www.genome.utah.edu/DMD. At this time, there is a significant cost for this testing.)

PTC Therapeutics literature describes PTC124 as a small-molecule drug that does not pose the delivery challenges that have limited gene therapy. The company says PTC124 is practical to deliver, does not alter genes, and does not require foreign genetic material or viruses.

For further information from PTC Therapeutics, contact Kerri Donnelly at (908) 222-7000, ext. 112.