Posted on 04/23/2007 3:37:59 PM PDT by 2ndDivisionVet
A pill that can correct a wide range of faulty genes which cause crippling illnesses should be available within three years, promising a revolution in the treatment of thousands of conditions.
The drug, known as PTC124, has already had encouraging results in patients with Duchenne muscular dystrophy and cystic fibrosis. The final phase of clinical trials is to begin this year, and it could be licensed as early as 2009.
As well as offering hope of a first effective treatment for two conditions that are at present incurable, the drug has excited scientists because research suggests it should also work against more than 1,800 other genetic illnesses.
PTC124 targets a particular type of mutation that can cause very different symptoms according to the gene that is disrupted. This makes it potentially useful against a range of inherited disorders.
The same drug could be given to patients with Duchenne muscular dystrophy, the most serious form of the muscle-wasting condition, cystic fibrosis, which mainly affects the lungs, and haemophilia, in which the blood does not clot. It can be taken orally, and safety trials have not revealed any major side effects.
“There are literally thousands of genetic diseases that could benefit from this approach,” Lee Sweeney, of the University of Pennsylvania, who is leading the research, said. “What’s unique about this drug is it doesn’t just target one mutation that causes disease, but a whole class of mutations.”
In most genetic conditions, between 5-15 per cent of cases are caused by a defect called a “nonsense mutation”. Genes are instruction manuals for cells to make proteins, but nonsense mutations in effect introduce a command halfway through that stops production. The kind of protein disrupted determines the nature of the disease.
In Duchenne muscular dystrophy, for example, the protein necessary for normal muscle development is not made, and the fatal wasting disease is the result. In haemophilia, it is the gene for the clotting agents factor VIII or factor IX that is disrupted.
PTC124 works by binding to a part of the cell called the ribosome, which translates genetic code into protein, and allows it to ignore nonsense mutations. The gene can be read straight through and a normal protein is produced.
The beauty of the drug is that it should be useful with any disease caused by a nonsense mutation, no matter what its outward effects. The error is not corrected, but ignored. Patients would have to take the pill throughout their lives.
PTC124, which is made by PTC Therapeutics, has been staggeringly successful in animal models. A study published today in Nature shows that in mice with a nonsense mutation that causes Duchenne muscular dystrophy, the drug starts dystrophin production and restores their muscles to health.
The drug has passed safety trials in humans, and the results of phase-two trials on cystic fibrosis and Duchenne muscular dystrophy will be published shortly.
About 13 per cent of patients with Duchenne muscular dystrophy have a nonsense mutation and should respond to the drug. It would not be suitable for treating different mutations in the dystrophin gene, or diseases not caused by nonsense mutations.
Other diseases that can be caused by nonsense mutations include beta thalassaemia, a blood disorder, and Hurler syndrome, in which children’s mental and physical development stops and most patients die by the age of 10.
I wonder if the “gay rights” lobby will stil argue that homosexuality is genetic?
If there is any biological basis for homosexuality, it isn’t likely that this will affect it.
But let's say someone discovers a genetic basis and a treatment for it. I think the "gay rights" lobby would be opposed to it.
Praise God if it is a wonder drug. I have a friend who has three girls with CF. What a miracle it would be if this were to be the answer for them.
Cheers!
Thanks for the ping!
Here's a link to the abstract.
Wilson’s Disease already has an effective treatment, but I wonder if this one will also work?
Does anyone know where to find a list of the 1800 diseases affected my these mutations??
I have four suggestions.
The quickest is enter nonsense mutations and inherited diseases into PubMed. Find a local library with a subscription to Nature. Buy "PTC124 targets genetic disorders caused by nonsense mutations," online from Nature. Contact Jane Baj, Associate Director, Corporate Director at PTC, Tel. 908-222-7000x167
jbaj@ptcbio.com
Thanks! This’ll keep me up for many nights... whew!
This is amazing!!
About PTC124PTC124 represents a first-in-class, orally delivered investigational new drug for the treatment of genetic disorders due to nonsense mutations.
Nonsense mutations are single-point alterations in the genetic code that prematurely halt the translation process, producing a shortened, non- functional protein. In pre-clinical trials, PTC124 allowed the cellular machinery to bypass the nonsense mutation, continue the translation process, and thereby restore the production of a full-length, functional protein.
PTC124 has demonstrated activity in preclinical genetic disease models harboring nonsense mutations. In Phase 1 clinical studies, PTC124 was generally well tolerated, achieved target plasma concentrations that have been associated with activity in preclinical models, and did not induce ribosomal readthrough of normal stop codons. Pharmacokinetic modeling of the Phase 1 results has allowed development of a dosing regimen for the Phase 2 studies in cystic fibrosis (CF) and Duchenne muscular dystrophy (DMD).
It is estimated that 10% of the cases of CF and 15% of the cases of DMD are due to nonsense mutations. In addition to CF and DMD, other potential indications include hemophilia, neurofibromatosis, retinitis pigmentosa, epidermolysis bullosa, and lysosomal storage disorders. PTC124 may represent a unique opportunity to use a single small-molecule drug to address multiple chronic and life- threatening diseases of high unmet medical need. The FDA has granted PTC124 fast-track designation for the treatment of CF and orphan drug designations for the treatment of CF and DMD due to nonsense mutations.
PTC124 has also been granted orphan drug status for the treatment of DMD and CF by the Committee for Orphan Medicinal Products (COMP) of the European Medicines Agency (EMEA). PTC124's development is supported by grants from the Muscular Dystrophy Association (MDA), Cystic Fibrosis Foundation Therapeutics, Inc. (CFFT), FDA's Office of Orphan Products Development (OOPD), and by General Clinical Research Center grants from the National Center for Research Resources (NCRR).
www.fsp-info.de/neufsp/PTC124_background.pdf
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