PTC124, a Drug Against Genetic Diseases: Overview

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 airwaysAlthough 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:

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