Tuesday, September 05, 2006
Most news articles about cystic fibrosis follow the same basic outline. They begin with a story about a kid who "just wants to be like the other kids", then they go into minimal detail about the medications the child must take to be normal. After than they say how the future looks grim for said tot, unless of course, these new medications can be approved in time!
The lyrics may be different, but the tune remains the same. Even Forbes magazine, which rarely resorts to what I call the "tear-jerker tactic," has brought me to a new level of cynicism by publishing Mary Ellen Egan's article "Breathing Easier."
I'm willing to wager that Ms. Egan had minimal knowledge of cystic fibrosis before she wrote the article. I have read other examples of her writing and they too are very formulaic. Although I'm not particularly impressed with her writing style--even the article's title makes me cringe as I search desperately for an adverb accompanied by a modifier--I am pleased that she has attempted to garner some publicity for cystic fibrosis.
Unfortunately, not all of her facts about the disease are correct. She states that the average age of CF sufferers is 37. In point of fact, the median survival rate is approximately 37 years old. This means that half of CF patients will expire before this age, and the other half after. Based on the number of patients in the CF registry, one can reasonably assume that there are literally thousands of adult patients out there. Thousands.
We're the ones who are in more urgent need for medical breakthroughs. In my opinion, something better than finding medications to halt the progressive decline in lung function would be developing those that could reverse it completely.
Mary Ellen Egan
Now researchers hope new compounds may halt the deadly progression of cystic fibrosis. Inspire's drug, denufosol tetrasodium, emerged in the early 1990s from research by Dr. Richard Boucher at the University of North Carolina at Chapel Hill.
Patients with CF produce a defective form of a protein called CFTR (cystic fibrosis transmembrane conductance regulator) that screws up the inflow/outflow process. Boucher long suspected that epithelial cells have an alternative chloride transport channel; stimulate the right receptor, and he might jump-start the backup channel.
In 1991, after 15 years of searching, Boucher and his UNC lab coats discovered a nucleotide called uridine triphosphate (UTP) that activates this alternative chloride passageway. UTP turns on P2Y2 receptors--protein molecules on the surfaces of mucosal cells. These receptors prompt the cells to secrete salt (which draws water onto the airway surface) and prompt the hairlike cilia on cell membranes to beat faster to sweep mucus out of the airways and into the trachea, where it is disposed of by swallowing or coughing.
UNC licensed the breakthrough to Inspire in 1995. Inspire raised $9 million to develop a compound that would mimic UTP, tapping venture capitalists at Burr, Egan Deleage & Co. (now Alta Communications), Domain Associates and Medical Science Partners. The firm's scientists spent five years developing a synthetic version of UTP, now called denufosol, which can be inhaled through a nebulizer. Compound in hand, the company went public in August 2000; since then its shares have dropped 73%, in part because of higher R&D costs.
Vertex's compound, VX-770, would go a step further than Inspire's drug. It tries to restore function not only to the lungs but also to other organs affected by CF. VX-770 resulted from a five-year collaboration between Vertex and the Cystic Fibrosis Foundation. Vertex landed $13.3 million from the group to work on the compound and received a total of $40 million in foundation grants (although the organization doesn't own an equity stake in Vertex).
Instead of switching on a backup chloride channel like Inspire's drug, VX-770 works directly on the faulty CFTR channel. It targets parts of the CFTR protein involved in the opening and closing of the CFTR channel, propping open the protein to afford a more normal flow of chloride.
In young patients the pancreas and digestive tract also may benefit from the drug, says Vertex Chief Medical Officer John Alam, because the CFTR function is suspected to play a role there as well.
"I think it's a terrific idea," says UNC's Boucher, although he allows that VX-770 is only in early-stage trials. "There's hope now that you could take a pill and fix CF in the lungs, pancreas and other organs," he says. Patients may benefit from both the Vertex compound and Inspire's denufosol, he adds. "In college kids, who typically have significant amounts of lung damage, denufosol can keep the healthy portions of the lung healthy."