Drug to beat serious genetic disorders; cystic fibrosis success

A new investigational drug, potentially able to treat up to 2400 different genetic disorders, has been shown to induce production of a vital protein missing in patients with cystic fibrosis, the UK's most common life-threatening inherited disease. The drug, known as PTC124, could be used to treat the 5-15% (and in some cases up to 70%) of genetic disorders caused by a class of genetic mutations which interfere with the production of vital proteins in the body, according to scientists at PTC Therapeutics, Inc. who discovered PTC124.

Large-scale trials on patients with the childhood muscle wasting disease 'Duchenne muscular dystrophy' are already underway at 38 sites worldwide, with a similar study in cystic fibrosis patients due to start later this year. This is the first large-scale international cystic fibrosis trial for PTC124 said Dr. Stuart Peltz, cofounder and CEO of PTC Therapeutics, Inc. who are sponsoring the research.

Dr. Peltz told delegates at the BSHG annual conference today: 'Initial studies in animal models and early clinical trials have been very encouraging: In mice with the rodent version of Duchenne muscular dystrophy (DMD) we saw the muscle function normally lost in this disease restored to normal. In our latest trial, the majority of the 23 cystic fibrosis patients treated with PTC124 showed significant improvements, with over half entering the normal range of chloride channel function. The next step will be to investigate the longer-term effects of the drug in larger groups of cystic fibrosis and DMD patients in order to evaluate its potential clinical benefit.'

People with cystic fibrosis (CF) have a mutation in both copies of their 'CFTR' gene (one inherited from each parent), which disrupts a protein controlling salt and water levels in the body. Without the protein, their bodily fluids become abnormally thick and sticky, causing breathing and digestive problems. About 10% of CF patients have a type of mutation - known as a 'nonsense' mutation - which creates a rogue 'stop' signal in their CFTR gene, preventing production of the full-length functional protein.

Peltz said: 'PTC124 works by overriding the cell's protein-translation machinery into ignoring the premature stop signal, thereby allowing complete, functioning proteins to be produced. By targeting the underlying cause of the disease, PTC124 is one of the first drugs to put the concept of personalised medicine into practice.'

'Nonsense' mutations are found in up to 2400 other genetic diseases which may also be treatable with the new drug, taken orally throughout the patient's lifetime. The results of both the CF and DMD trials are expected in late 2010.