Rare Diseases and Hard To Treat Disorder and Symptoms with William Gahl

In this TED talk, William Gahl discusses the reality of rare and hard to treat diseases and what we can do to help save lives in a bureaucratic environment.

The National Institutes of Health in Bethesda, Maryland established an Undiagnosed Diseases Program. This program has as it’s goal to try to find the diagnosis in patients with long-sought after diagnosis and also to find out new diseases so we can make new discoveries.

There are over 5,000 applicants for this program and 1,800 individual charts. Over 400 individuals and have been accepted and the program has allowed for 300 to be seen so far. The results have been 50 or 60 diagnosis of really rare diseases.

The program has the advantage of having access to the experts at the NIH (National Institutes of Health) clinical center which is the largest clinical research hospital in the world.

In addition, the program has access to use the human genome project which annotates the 3.2 billion bases available that tells us where genes are – and the advantage of very modern techniques.

There are over 6,000 rare diseases and these affect up to 25 million Americans. They’re defined by law as disorders that affect fewer than 200,000 each, but together they affect the whole large number. It turns out there are only a few hundred treatments for these. Rare disease treatments are difficult to come by. Why? Because it’s not profitable for pharmaceutical companies to invest in a disorder that involves only 20 or 50 – or even 500 people.

So it falls upon the National Institutes of Health and upon physician investigators to pursue treatments for these diseases.

Here is something you might find impossible to believe… We have potential treatments that make sense, that have presumably very few side effects and yet we are not allowed to use them.

Why is that?

It turns out that The Food and Drug Administration ensures the safety of our foods and of the drugs that come to us, and they do a wonderful job of this, but there is one issue; for rare diseases they apply the same criteria for the use of an investigational drug as they do for common diseases. In fact, the dictum the Food and Drug Administration when investigational new drugs come before them, is that people with rare diseases deserve the same protection as other human subjects.

When you apply to the FDA to use an investigational drug (called IND – investigational new drug application) and the FDA requires that animal studies be done, along with a lot of toxicity studies, etc., it is very expensive, so much that the drug companies don’t really pursue it.

This is where the paradigm shift of Risk vs Benefit makes more sense. Especially since the risk of not treating some individuals with rare diseases is sometimes a certain death. Investigational drugs are – and have been for 50 years an accepted ethical principle.

Ironically, the system used to work better a few years back. In 1994 when the drug Cysteamine was approved there were no animal studies required of it. In other words, the FDA used its discretion and scores of individual lives were saved and positively affected by that decision.

On the other hand, in the case of of a little girl born in 2007 with Canavan disease which is a neuro degenerative disorder where the central nervous system does not function, and kids usually die in the first three or four years of life, the FDA failed to use it’s discretion resulting in the death of this little girl.

In this case, the team of doctors felt they had a window of time of about twelve weeks or so to treat her. The doctors had everything in place and where ready to administer her with Glyceryl Triacetate which was donated by a company called Cognis. The nurses where ready, the new drug exemption was submitted to the FDA and the doctors got approval for the protocol from the FDA’s institutional review board, but in the end the FDA failed the family and the little girl died.

They (the FDA) required the doctors to conduct the following chronic toxicity studies and provide full reports for their review and evaluation; A 6 month oral toxicity study in a rodent species, a 9 month oral toxicity study in a non-rodent species. The studies should be conducted on neonatal animals to match the age groups of the patients being enrolled in the proposed clinical study – along with three pages of other requirements.

So what is the solution to this problem?

Well, the Food and Drug Administration has the opportunity to use discretion in this regard. They actually did so recently with respect to the drug Makena which is for premature pregnancy. They have that capacity and we need for them to use it. And we need the FDA regulators to look at this as a risk benefit ratio – which again is an ethical principle that we have all adhered to for the last 50 years or so, because the risk many times for these individuals is certain death.

People in the rare and hard to treat disease community want to be protected, but they don’t want to be protected to death.

Luckily, there are officials within the government that are addressing this issue. In particular the NIH-FDA Leadership Council with Dr. Francis Collins and Dr. Peggy Hamburg and the SIMD (Society for Inherited Metabolic Disorders.)

What else can be done? We as citizens can do our part because this affects us all. We can write to our newspapers about this, or if you are in healthcare policy you can consider pursuing this as a project. You can always submit your comments to the www.hrsa.gov website.