After about 13 years of meticulous discovery work, Dr. Steven Idell, Ph.D., is preparing for his latest drug therapy to go to the first phase of human clinical trials.
The UT Health Northeast researcher is collaborating with Dr. Andrew Mazar from the Center for Developmental Therapeutics at Northwestern University in Evanston, Ill., on a program that could provide relief to patients suffering from a debilitating lung condition. His drug, single-chain urokinase plasmogen activator, or scuPA, is a clot-busting enzyme therapy that targets fluid accumulated around a patient's pleural cavity, the space between two thin membranes that line and surround the lungs.
Fluid buildup in this space occurs in patients who have had severe pneumonia or cancer. Each year in the U.S. and Great Britain, there are 1 million cases of pneumonia that require hospitalization.
As many as 4 million have "walking pneumonia," Idell said. Of the people with pneumonia, 400,000 develop pleural effusion, or fluid surrounding the lungs.
When the fluid becomes jelly-like, making it difficult for the lungs to expand, it's as though a patient's lungs are trapped inside hardened Jell-O.
"Normally, the lungs move inside the chest walls very easily, but (fluid) gets tacked up against the chest wall, and it doesn't move freely," said Dr. David Griffith, a pulmonologist at UT Health Northeast. "It's hard to breathe."
Fluid is drained through a chest tube or patients undergo surgery. Idell said between 40,000 and 80,000 cases each year require drainage. Use of the drug would be safer than using a needle to drain fluid from a lung, Idell said, as it could damage tissue or collapse the lung. The fluid also may be infected. With medically fragile patients, surgery isn't a good option. Surgical removal is painful, dangerous and doesn't always work, which is where Idell's drug comes in. He said scuPA limits potentially harmful effects.
ScuPA is a biological drug. It's a compound made from cells in the lining of the lungs, but the body does not make enough of it to prevent clotting.
"We're making essentially what the body is making," Idell said. "The way we do it is by putting the gene into manufacturing great cells."
The new drug is in the same class as tPA — tissue plasminogen activator — used to treat heart attack and stroke. But scuPA has properties that are an advantage for people afflicted with fluid in the pleural space. The drug resists major inhibitors, or things that may keep the drug from working. It also functions gently.
"We think it's less likely to cause bleeding than commercially available alternatives," Idell said.
With FDA approval of scuPA, established doses will be tested, something commercially available alternatives had not gone through.
Manufacturing started several months ago and will be completed by the third quarter of this year. Clinical trial testing could begin within six months after that. The first phase in clinical trials tests the safety of a drug. Trial sites will be in different UT System health component locations. About 15 patients will be involved in the first phase. This trial will be unique in that it must be given to patients who have the fluid present so everyone in the safety trial will be a candidate for the drug. However, most drugs are tested on healthy individuals in the first phase.
"The first thing you want to do is establish that it's safe in humans," Idell said. "We believe that will be the case because it's already been given intravenously to hundreds of patients when it was used for stroke and heart attack dosing."
The journey of a researcher's idea for a new drug is a long road traveled. According to the U.S. Food and Drug Administration, five out of every 5,000 compounds considered for drug candidates will be judged safe enough to be tested on humans. One of these five will gain approval from the FDA before being marketed as a new drug.
Idell is optimistic that scuPA also will work on idiopathic pulmonary fibrosis, or lung scarring with no known cause. If it did, that would be the "pie in the sky" that Griffith has been waiting for.
"If this drug turned out to be useful for pulmonary fibrosis — which is scarring inside the lung — that would be huge. There is no therapy for lung fibrosis right now. The only therapy of any value is lung transplantation," he said.
The project is being funded by the National Institutes of Health. Throughout the years, Idell has secured more than $10 million for scuPA research.