Arginine Butyrate Heals Sickle Cell Leg Ulcers

December 10, 2002

Dec. 10, 2002 (Philadelphia) — Researchers working with an experimental drug for sickle cell anemia noticed an unexpected side effect: the incidental healing of debilitating leg ulcers in seven patients.

That serendipitous observation led to a 25-patient phase II study in which treatment with the compound, arginine butyrate, healed 17 of 37 leg ulcers. In contrast, among 24 ulcers that received standard local care for wounds, complete healing was documented for one ulcer.

Several of the participants had suffered with large open sores for decades, according to investigator Susan Perrine, MD, of Boston University School of Medicine in Massachusetts. One woman had leg ulcers for 30 years, Dr. Perrine reported in a presentation here at the American Society of Hematology annual meeting.

The investigator showed dramatic before and after photographs of legs from several patients who benefited from the treatment. The mean initial area of ulcers in the arginine butyrate arm of the study was 50.8 cm2 — nearly twice the 26.4 cm2 in the control group.

Within three months of treatment, the area had been reduced by 53% in patients who received arginine butyrate, but the area was reduced by 9% in the control arm. Dr. Perrine said the researchers don't know why the compound heals these ulcers.

H. Grant Prentice, MD, of the London Clinic in the U.K., called the study "extremely important." The former head of hematology at the Royal Free Hospital in London, Dr. Prentice said the most common therapy for leg ulcers associated with sickle cell disease is hydroxyurea. "It's not very effective, and the patients don't like to take it," he told Medscape.

About 25% of sickle cell patients suffer from leg ulcers, according to an earlier study of 2,000 patients that Dr. Perrine cited at the start of her talk. In the United States, she said, the typical sickle cell ulcer lasts as long as three years; in the Caribbean more than nine years is common. Even if they are cured, between a quarter and a half of these ulcers will recur.

Despite their prevalence, the ulcers are not well known, even in the sickle cell community, according to Dr. Perrine. They tend to occur in adults, she said, explaining she had little experience with them because she works in pediatrics.

Patients in the treatment arm of the trial received 500 mg/kg of arginine butyrate six hours a day three days a week for twelve weeks. Although hydroxyurea is used, she said there is no standard regimen for these sores. The control group was treated aggressively according to local standards for wound healing, but no particular protocol was used in the six-center study.

Although the study ended after three months, patients were allowed to continue for 16 weeks if their ulcers were closing with arginine butryate. Within five to seven months, a 10-fold increase in wound healing was reported.

Dr. Perrine said the investigators plan to seek funds for a phase III trial. The pilot study was conducted with support from the U.S. Food and Drug Administration's orphan drug program, she said. Arginine butryate is an experimental compound and is not yet commercially available.

ASH 44th Annual Meeting: Abstract 26. Presented Dec. 8, 2002.

Reviewed by Gary D. Vogin, MD