Sunday, April 22, 2007

Revolutionary New Therapy for Inherited Diseases

In today’s news is an announcement from PTC Therapeutics of New Jersey that their lead drug, PTC 124, has been shown successful at reversing muscular dystrophy in mice.

MD is not an autoimmune disease. However, PTC 124 has the potential to treat a host of inherited, genetic diseases caused by nonsense mutations (in our genes—DNA). Some (many?) autoimmune patients could be helped.

In my opinion the following immune dysfunctions are most likely to have a gene malfunction that this compound could help—Crohn’s/colitis/IBD, mastocytosis/mast cell activation disease, anaphylaxis, angioedema (HAE), and severe forms of food allergies as well as severe asthma. Almost any genetic disease that runs in families might be helped. So my list could be musch too short.

PTC 124 is not gene therapy rather it helps existing genes that are malfunctioning to function well enough to end disease symptoms. It allows needed proteins to be made even when there is a nonsense mutation in the middle of a DNA sequence. It works in a similar way to the intravenous antibiotic Gentamicin but with less toxicity. It is administered orally—another plus.

It is already being tested on humans in phase II clinical trials for Duchenne’s muscular dystrophy and cystic fibrosis. Preliminary results look good.

The problem will be identifying the subset of patients who can be helped. Right now only genetic sequencing can be used in advance to determine who might be helped. Genetic sequencing is expensive and is not available for the vast majority of genetic diseases (like autoimmunity). However, if it is found to have a good safety profile, it might be tried on a “well it couldn’t hoit” basis on large numbers of diseases that might respond.

Here is a quote from the article:
"This new class of treatment has the potential to help a large number of patients with different genetic diseases that have the same type of mutation," says senior author H. Lee Sweeney, PhD, chair of the Department of Physiology at Penn. This genetic flaw causes from 5 to 15 percent (and in a few instances up to 70 percent) of individual cases of most inherited diseases, including DMD, cystic fibrosis, and hemophilia.

Don't get your hopes up for PTC124's quick use for our inherited, genetic diseases. This cure is decades away from use in the autoimmune community. If PTC Therapeutics allow PTC124 to be used in a large numbers of patients, they would jeopardize it’s possible FDA approval costing them millions of dollars. The company must carefully pick patients who are the most likely to benefit.

Here is why. If “risky” patients who do not meet inclusion criteria are allowed the medication under compassionate use exemption, the company must report any negative complications. The sickest at risks patients are the most likely to have complications. Those reported complications are used against the company during the final FDA approval process. It is contrary to a company’s best financial interest to allow much compassionate use.

There will be no expanded-access program for PTC 124. Here is what PTC Therapeutics says on the matter:
“At this time, an expanded access program would be premature. Although the early data in cystic fibrosis and Duchene muscular dystrophy are promising, the results are very preliminary, and were obtained from a small number of patients receiving PTC124 for a short period of time. Conduct of an expanded access program at this time might result in unacceptable risks for patients and might jeopardize the development of PTC124 so that it cannot become available for all patients who might benefit if its efficacy and safety are eventually proven.”

Why would expanded access (compassionate use) jeopardize the development (approval) of PTC124? Because of the stupid insistence of the FDA to penalize companies that are trying to do the right thing. Complications in patients who at most risk should not be counted against the approval of the new medication (IND). Those patients are dying anyway. At least give them a chance at a treatment. Give them some hope. Otherwise the sickest patients get new treatments last.

FDA rules must change if we are to get the cures in a timely manner. If you or your loved ones do not mind waiting in pain and dying quietly, then you should be fine with the FDA policy of penalizing companies for allowing for compassionate use. If you would like a cure NOW, perhaps you would be willing to call the FDA and complain. Let your US senators and Congress person know as well.

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