Inspired by biotechnology executive John Crowley's efforts to save his children, the movie Extraordinary Measures shows basic science and biotechnology teaming up to help researchers develop a treatment for a rare and fatal neuromuscular disorder.

With a prevalence of one in 40,000, according to a 2007 review published in Pediatrics, Pompe disease results from a recessively inherited deficiency in the gene encoding acid alpha-glucosidase (GAA), an enzyme that converts glycogen to glucose. The defect results in a build-up of glycogen in the lysosome, a saclike storage organelle in the cell that acts as a waste-disposal system, leading to muscle weakness, organ damage including the brain, and possible death. (The infantile variant of the disease is fatal without treatment, usually within two years).

In 1998, Crowley teamed up with glycobiologist William Canfield, founder of Novazyme Pharmaceuticals Incorporated (now part of Genzyme Corporation). Subsequent research at Genzyme in collaboration with scientists from Duke University led to the approval by the U.S. Food and Drug Administration in 2006 of Myozyme under the Orphan Drug Act, which allows Genzyme to sell the drug without competition for seven years.* The treatment can cost up to $300,000 a year, according to The New York Times.

Jonathan Cooper, head of the Pediatric Storage Disorders Laboratory at King's College London's Institute of Psychiatry, explains why Pompe disease is so rare, hard (and expensive) to treat.

[An edited transcript of the interview follows.]

What is Pompe disease?

Pompe disease is one of many lysosomal storage diseases, in which you have a defect in the lysosome. In this case the gene should be making [acid alpha-glucosidase], but it doesn't. Then the lysosome doesn't work and things build up in cells that shouldn't be there. Unfortunately these types of diseases are progressive and fatal. You discover very quickly that there's a gene defect and your child will suddenly start showing signs of progressive disease.

Why is it classified as an orphan disease?
They're called orphan diseases because we don't have treatments for them. That's the worst part of the diagnosis for these children. We have no drugs to treat them with.

Why is it so rare?
To get the effects of the disease, you need to have two mutant copies of the gene. Somewhere back in the mists of time there will have been a mutation. It is passed on from generation to generation. Then, two parents will be carriers, and each time they decide to have a child there is a 25 percent chance of the child having the disease. There is a 50 percent chance that the child will be a carrier.

Why does it take so long to find treatments?

You first have to figure out what the genetic defect is—a long process.

It's also harder to get funding for that sort of rare disease research. Every time you enter a grant competition you're competing with everybody else—Alzheimer's researchers, Parkinson's researchers—so, unsurprisingly, the grant funding authority often opts for where they'll get the most for their money. Getting pharmaceutical companies interested in funding research is hard because of the limited profits.

How do scientists and drug companies work together?

If you have a basic scientist working on a particular disease who has some insight into the disease mechanism, then that person can be useful to a drug company. Drug trials require a preclinical development phase using animal models, and basic scientists are very useful for this. Sometimes the scientist will work for the company, sometimes they'll collaborate with the company.

Why is the treatment for Pompe disease so expensive?
Enzyme-replacement drugs are expensive to make and they need to be given frequently. They're quite effective but only have effects within the body. If you have a disease which affects the brain, you have considerably more problems because you have to get [the drugs] into the brain.

Can cheaper therapies be developed?
This is where the issue of intellectual property comes in. If a company has intellectual property on the genetic defect, like Genzyme does, they have exclusive rights to work on finding ways to make and deliver drugs to treat it. Until the intellectual property expires, they have the sole rights for working on that gene from a scientific standpoint.

Are there alternatives that could be pursued once the intellectual property expires?
You could use gene therapy to transfer the deficient genes into the cells and get them to make the enzyme for you. But you need finances to be able to do that type of research.

What if people can't afford the treatment?
There are a variety of philanthropic goodwill programs that are giving a discounted rate on the drugs or actually giving them away.


*Note (1/26/10): This sentence was edited after publication. It originally identified Crowley and Canfield as the developers of Myozyme.