Hearing loss and prevention research

[RandyW]

SIU scientist finds way to help radiation patients

Discovers protein component mix that alleviates soreness

By DEAN OLSEN

STAFF WRITER

Published Sunday, December 17, 2006

Almost everyone who receives radiation treatment for oral cancer faces a painful and potentially devastating side effect.

The radiation creates sores and inflammation inside the mouth and throat that can interfere with eating and drinking. The problem, known as mucositis, can become so uncomfortable that the normal six or seven weeks of radiation treatment must be stopped while symptoms subside. Some patients have to use feeding tubes.

Relief may be on the way for many patients, however, as a result of a decade of research by Kathleen Campbell, a scientist at Springfield's Southern Illinois University School of Medicine.

Mucositis affects 40,000 to 60,000 people with head and neck cancer each year and up to 600,000 Americans each year who undergo radiation treatment for cancer of the mouth, throat, colon, lung or breast. In rare cases, the complication can lead to death.

Campbell's studies have helped lead to the development of an orange-flavored liquid containing a substance called D-methionine, a component of a protein commonly found in cheese and yogurt.

In a small group of patients and animal studies, the substance has prevented or reduced the severity of radiation-related inflammation in most cases.

The experimental treatment, already is being tested in oral-cancer patients in India. It is about to be offered to Americans at Johns Hopkins University Cancer Center in Baltimore.

"With positive results to date, it's the most exciting thing in my professional career," said Campbell, 54, a South Dakota native and member of SIU's faculty since 1989.

Her stepfather went through radiation therapy for cancer four years ago and died as a result of mucositis complications.

Future treatments based on the patents that Campbell developed at SIU for the use of D-methionine also could protect cancer patients' hearing from the effects of a common chemotherapy drug called cisplatin. And D-methionine could protect the hearing of patients who receive a group of antibiotics commonly used in poor countries.

The amino acid appears to slow the chemical chain-reactions that lead to development of "free radicals." Researchers know that free-radical damage can result from radiation, causing the lining of the mouth to suffer. Free radicals also can damage the inner ear.

Researchers have tried for decades to develop protective agents to stop the proliferation of free radicals without reducing the beneficial effects of radiation, chemotherapy or antibiotics.

Campbell said her interest in protective agents originated from frustration she felt while working as a clinical audiologist at the University of Iowa in the 1980s.

Many cancer patients lost hearing because of chemotherapy drugs. "I felt powerless to do anything," she said.

She earned a doctorate in hearing science at Iowa and has researched drugs' effects on hearing for 18 years. She began research on potential protective agents about 10 years ago and has examined the effect of D-methionine on rats, chinchillas and other laboratory animals.

She said she searched through thousands of studies before deciding to focus on D-methionine. Early research indicated it was safe, easy to produce and potentially beneficial in blocking free-radical production, she said.

Her patents on use of the chemical are owned by SIU and were licensed in 2004 by Molecular Therapies Inc., a company based in Ann Arbor, Mich. Licensing gives a company the right to develop discoveries into proposals for clinical trials that could lead to approval by the U.S. Food and Drug Administration and widespread use.

But the road to market can be treacherous.

"Out of a thousand patents, only five get licensed," Campbell said. "So, getting licensed is a huge step. But out of those five that get licensed, only one ultimately gets approved by the FDA."

Federal, state and private grants totaling $1 million to $2 million have propelled Campbell's research on D-methionine at SIU so far. Molecular Therapies has spent another $5 million to $6 million on clinical trials, according to Prasad Sunkara, the company's chief executive officer.

If the trials are successful, Sunkara said additional testing to make the therapies available in Illinois and to win FDA approval in the next five to seven years could cost the company $60 million to $100 million.

If one of the treatments is approved by the FDA and becomes widely used, SIU could receive millions of dollars in profits, with up to half going to Campbell. But she knows that the possibility of such financial success is far from certain.

"I tell people that I have not quit my day job," she said.

The U.S. Department of Defense has shown interest in how her research could benefit soldiers, who frequently lose their hearing from explosions and gunfire.

"Over a third of military personnel end up with disability pay specifically for noise-induced hearing loss," Campbell said.

Her research on how D-methionine might protect against noise-related hearing damage hasn't progressed enough to conduct testing in humans. But the results are promising. Campbell said most chinchillas exposed in the lab to loud noise for six hours have seen their hearing restored after receiving D-methionine an hour later.

Aircraft mechanics, mine workers, rock musicians, people who survived auto accidents when an air bag exploded - all have experienced permanent hearing loss and could benefit if clinical trials go well, she said.

"What if you could go out and take a pill or drink this orange soda and make sure this hearing loss doesn't become permanent? Wouldn't that be great?" she asked.

Clinical trials on D-methionine's use in the prevention of mucositis are furthest along, with Phase 2 trials involving at least 90 people to be completed by fall 2007.

FDA approval of a drug to treat mucositis in a broad range of cancer patients would be a "phenomenal breakthrough," said Dr. James Malone, an SIU head and neck cancer surgeon.

"It would be of tremendous benefit to the patient and have a huge impact on not only their quality of life but probably their ability to complete their treatment."

Dean Olsen can be reached at 788-1543 or dean.olsen@sj-r.com.