PTC124, a Drug Against Genetic Diseases: Overview May 4, 2007
Posted by Bertalan Meskó in Gene, Genetic condition, Genetic testing, Health, Invention, Medicine, Syndrome, genetics, science.trackback
I’ve already written about the Times Online article (Daily pill to beat genetic diseases), but I would like to give a clear overview of this “miracle-drug”. The story of PTC124 is not new, it goes back to 2004. Anyway, what is it about?
PTC124 is a novel, orally administered small-molecule compound that targets a particular genetic alteration known as a nonsense mutation. Genetic disorders occur as a consequence of mutations in an individual’s DNA. Nonsense mutations are alterations in the DNA that, when transcribed into mRNA, introduce a premature translation termination codon. This change halts the ribosomal translation process at an earlier site than normal, producing a truncated, non-functional protein.
So PTC124 binds to the ribosome, ignores the nonsense mutation, but doesn’t repair it and make the genetic disease “go away” as it makes it possible for the body to produce the proper protein. Just some examples for genetic diseases caused by nonsense mutation (of the approximately 1800 similar diseases):
As it doesn’t repair the mutation, patients have to take the pill throughout their lives. Here is an image, how it works exactly:
OK, it sounds fantastic, but what about the studies?
You can read more about the phase 2 clinical trials of Duchenne muscular dystrophy and cystic fibrosis as well. The description of phase 2 clinical trials for Duchenne muscular dystrophy says:
The results from this study indicate that PTC124 is well-tolerated and imply pharmacological activity based on preliminary data that suggest increases in dystrophin in muscle biopsies in a number of patients and statistically significant improvements in creatine kinase in blood… several parents and teachers have reported that boys participating in the study have had improvements in terms of greater activity and increased endurance during treatment.
Phase 2 clinical trials for Cystic Fibrosis:
Across the two studies, at both PTC124 dose levels tested, TEPD assessments showed statistically significant improvements of average CFTR-dependent chloride secretion in the airways… Although a formal symptom assessment was not a component of the Phase 2 program, a number of patients described decreased sputum volume and thickness, decreased frequency and severity of coughing and a better sense of well-being during PTC124 therapy.
I have to admit that these results are incredible, look how dystrophin was rebuilt:
It also sounds great, though I think we should be a little skeptic as new therapies are always presented as miracle methods in spite of side effects and non-expected mistakes. Anyway, it might be a really exceptional improvement in the future. I’m eagerly waiting for the results of the next clinical trials. Until then, in case you’re still interested, read more about PTC124:
- PTC Therapeutics
- Scientific Background (pdf)
- PTC124 Frequently Asked Questions
- Personalized Medicine Blog
- PTC124 targets genetic disorders caused by nonsense mutations, Nature 447, 87-91 (3 May 2007) (abstract)
Related links:
What a great post. How come I never bumped into this great blog before. If you ever need any advice re: specialty or anything else send me a line.
-Steve
http://www.thegenesherpa.blogspot.com
You see,
the first thing to go is your short term memory. Of course…..
Remember, write everything down
Everything
-Steve
http://www.thegenesherpa.blogspot.com
Thank you for the kind words, Steven! You do the greatest blog on the subject, so I have a lot of things to learn from you…
And if you need a new collaborator who is a medical blogger and plans to spend his lifetime specializing in clinical genetics, send me a line.
[...] Sorry for including my submission, but this has become a tradition in Gene Genie, so I’d like to share my thoughts with you on PTC124, a new drug against genetic diseases. [...]
[...] Sorry for including my submission, but this has become a tradition in Gene Genie, so I’d like to share my thoughts with you on PTC124, a new drug against genetic diseases. [...]
To my best kowledge to overcome PTC induced NMD another amino acid has to be introduced in the growing peptide chain via a suppressor t-RNA. Thus, I wonder which amino acid was introduced in the described cases and if PTC124 will work with every PTC in every gene. Or will treatment of other PTCs result in a full length abeit non-functional proteins?
It’s interesting what you’re saying. Do you happen to know any kind of publications on the field?
I like to know if ptc124 will be suitable for post polio syndrums( PPS). That also damage muscles. Although mechanism is diffrent and PPS patients have very high level of CK in their blood. That can be said it is nerve related but end results are same. If any body have full knowledge of PTC124 working and are there any trials going on relative to polio effected patients.
PTC124 will only work on inherited diseases caused by a premature stop codon mutation in a gene. All genes have stop codons at the end, but the “premature stop codon” is a mutation which happens too early in the gene. Due to this mutation, the protein you need isn’t made or is too short.
PTC124 will not work on muscles or other parts of the body which are damaged by an infection like polio or by any other kind of physical damage - like an car accident.
PTC124 will ONLY help people who have a premature stop codon mutation, not any other kind of mutation.
[...] PTC124, a Drug Against Genetic Diseases: Overview Pompe disease, a rare but important genetic condition 10 Tips for How to Use Web 2.0 in Medicine 7 Tips: How to track the information you need! [...]
Will PTC-124 work on all nonsense mutations in mRNA? Like with all the stop codons UAA,UAG,UGA. Or just one type like the UAG?
It seems it would work with all nonsense mutations.