The economics of Duchenne has always been difficult due to the small population. Ataluren only got as far as it has because it potentially impacts many other diseases, most of which are more profitable. Drugs that only help Duchenne (like utrophin upregulators) will always face financial hurdles. Unfortunately, as science makes advances, the financial constraints have and will become more apparent and frustrating. I have been following all of this for over 12 years (son is now 14 and still walking). PTC, and it's joint venturers and investors, will not risk the success of this drug for Duchenne. My take on the low versus high dose is that the high dose might be producing an immune response to the dystrophin. No one knows how much dystrophin will be needed to improve function; and no one knows if we can restore a sufficient amount of dystrophin without triggering an immune response. If Ataluren is to be properly evaluated, we will need to know what % of dystrophin was produced in various muscles, and whether there is evidence of the body attacking the newly produced dystrophin. I am surprised we have no major statements regarding whether or not there was immune response to dystrophin at higher doses (if there was none, they should state that fact). If there is an immune response, these dystrophin replacement strategies will be set back even further. I have always thought utrophin is the only hope for boys alive today. But, as can be seen, upregulation is not easy from either a scientific or a financial viewpoint.
Unfortunately, nothing will happen overnight. Just look at the timlines for drugs for the most lucrative of diseases. I share your frustrations and have lived through them. More frustrating than the failure to get dystrophin in the muscle is the failure to pinpoint key downstream pathologies that might be targeted by existing drugs. As of today, we still depend on deflazacort and supplements.
I agree that it would be a good idea to include this question during the conference call, although I really think that an immune reaction to dystrophin would have manifested itself in a much more forceful way, causing the trials to be stopped immediately. I don't think that an immune reaction would limit itself to just preventing more dystrophin from being produced, while still allowing some dystrophin to be expressed in the first place. Either the immune system detects the new substance as foreign, in which case it rejects it outright, or it just allows it in. Also, regarding the comment by Cheri on boys who already had some dystrophin when admitted into the trial, I wonder how this could have been allowed. I would have thought that in order for a boy to be diagnosed with Duchenne Muscular Dystrophy (and therefore, to be admitted in the Ataluren trials), the histological exams should have shown zero dystrohin in the muscle cells, otherwise we would be in front of a Becker MD.
Thank you Ofelia. I guess that the division between DMD and BMD is becoming more and more blurred as reasearch progresses.
Yes, not much news really. Only the data already presented mid April. At this point, I really do not buy the fact that they do not have any biopsy data. I am sure they do have at least partial results. Also, the question about immune response was not asked.
There are many issues beyond the immune response and the levels of dystrophin required to have a prophylactic effect, and I suspect that is why PTC is sitting on their results.
As a parent I would be more concerned if they were releasing all their data, as it would signify they are finishing their work on the project and leaving it open for anyone else to come and "pick up where they left off".
Whilst it is frustrating that these things take time, from some of the conversations I have had with other researchers, there are some important considerations that must be addressed. These issues go beyond dystrophin expression and the 6MWT and cover proteins and enzymes that are independent of those associated with DMD.
Personally I would rather wait and know the drug I am giving is safe, than rush this process and blame myself later if things went horribly wrong. But that's just me - everyone's journey is different.
Ofelia Marin said:Yes, not much news really. Only the data already presented mid April. At this point, I really do not buy the fact that they do not have any biopsy data. I am sure they do have at least partial results. Also, the question about immune response was not asked.
Ofelia, please don't think I'm being negative or justifying the delays. I am basing my reply on the questions being raised in the research world driven by how PTC124 functions at a molecular level. There are also a lot of people that are mindful that just because you don't see a clinical sign or symptom does not mean that other cellular processes are not being disrupted ..... diethylstilbesterol taught the research/pharma industry that - and there are still compensation claims being paid for that one.
It is great that PTC will release some data in July, it might answer some of the questions parents have, or indicate the future direction of PTC124 in DMD research.