Hadassah researcher Prof Eitan Kerem. He hopes the drug will be able to treat other diseases caused by the nonsense mutation.Seminal research led by an Israeli team from Hadassah Hospital in Jerusalem may yield dramatic relief for cystic fibrosis (CF) patients in the next few years. It also opens up new opportunities and hope for treating genetic diseases such as muscular dystrophy.

The promising new oral drug, PTC124, is being developed by US biopharmaceutical company PTC Therapeutics, located in New Jersey, in conjunction with Hadassah’s researchers Prof. Eitan Kerem and Dr. Michael Wilschanski. It has already passed a milestone in drug development.

This month, the researchers announced positive results from their Phase II clinical trials in humans, and published their findings in the prestigious medical journal The Lancet. The orally administered pill helped 16 out of 23 Israeli study patients improve their chloride (salt) channel functioning.

A treatment for other diseases

“We hope the drug will be able to treat other diseases caused by the mechanism responsible for this mutation,” says Kerem, head of pediatrics at Hadassah University Medical Center on Jerusalem’s Mount Scopus.

“Israel has been pivotal in this work as approximately 60 percent of [CF] patients in Israel carry stop [nonsense] mutations,” Wilschanski, director of the Pediatric Gastroenterology Unit at Hadassah, tells ISRAEL21c.

Cystic fibrosis is an inherited chronic disease affecting about 30,000 Americans. The defective gene, of which there are more than 1,500 mutations, allows extra salt to enter one’s cells, causing the body to produce unusually thick, sticky mucus.

This life-threatening condition often leads to infection, and lung damage. Intensive treatments used today, says the Cystic Fibrosis Foundation, can prolong the lives of patients well into their 30s, 40s and possibly beyond, but a cure is very much sought after since the median age of survival (2005) is only 36.5 years.

PTC124 may be the life-saving answer for some. Research behind the drug was conducted in Israel, where investigators took advantage of the unusual genetic pool of Israeli cystic fibrosis sufferers – the majority suffering from a specific form of the mutated CF gene, caused by a “nonsense” mutation. In the United States, only about 10 percent of all cases arise from this type of mutation.

Opening a window in drug development

PTC124 works by stopping the ‘nonsense’ genetic defect, allowing the protein-making machinery of the patient’s cells to function as it should.

Even though this new drug candidate may only be effective in a fraction of American CF patients, the positive clinical results have opened a new window in drug development for a whole host of genetic diseases caused by nonsense mutations.

Since about one-third of all genetic disorders – about 2,400 known disorders – are caused by a nonsense mutation, cystic fibrosis patients are only the first of many other kinds of nonsense-mutation patients expected to benefit from this breakthrough.

PTC124 has been granted “orphan-drug” status by the US Food and Drug Administration for the treatment of Duchenne muscular dystrophy and CF, a special status which the US government grants in support of drugs for rare diseases.

PTC is also conducting clinical trials on PTC124 as a treatment for Duchenne muscular dystrophy, a particularly devastating disease which affects about 10,000 Americans. Meanwhile, a longer-term study on cystic fibrosis is planned for the United States, Canada and Europe.