Dr. Lawrence Hurst and Marie Badalamente, Ph.D, created a drug that treats people whose hands have been affected by Dupuytrenís contracture. Photo from SBU
December 27, 2012 | 10:14 AMWhat's the best way to free people from pain, earn U.S. Food and Drug Administration approval and change the way a disabling medical condition is treated? Slow and steady.
For 18 years, Dr. Lawrence Hurst and Marie Badalamente, Ph.D. conducted research and clinical trials to find a better way to treat Dupuytren's contracture. Dupuytren's twists the fingers into the palm, limiting hand function, sometimes severely. The problem is caused by too much collagen, the fibrous protein that gives ligaments and tendons their ropy structure.
Badalamente and Dr. Hurst found a way to dissolve the extra protein by injecting patients with a collagen-eating enzyme. For their work that led to a new drug, and for giving Dupuytren's patients a successful alternative to surgery, they are People of the Year in Science.
Dr. Hurst is professor and chairman of orthopedics at Stony Brook University School of Medicine, and chief of the division of hand surgery at the hospital. Badalamente is a professor in the department of orthopedics. Together they studied whether collagenase clostridium histolyticum — a collagen-destroying enzyme found in a type of bacteria —could break down the unwanted collagen in the hands of people with Dupuytren's. They isolated the enzyme in the laboratory and injected it into patients' contracted fingers.
Their idea worked. Clinical trials showed that after three injections, collagen fibers weakened substantially and patients could straighten their hands. Karen Mercaldo, who had Dupuytren's in both hands, volunteered to be part of SBU's clinical study. After the injections she could play the piano and viola again, and knit and type.
"To me, it was amazing," she said. Mercaldo traveled to Washington D.C. and testified to the FDA on behalf of the Hurst-Badalamente treatment. Today she has "a little bit of recurrence in one finger, but I still can do everything."
Badalamente and Dr. Hurst's work resulted in a new drug they developed at SBU: Xiaflex, approved by the FDA and marketed by Auxilium Pharmaceuticals, Inc. Dr. Hurst is a noted hand surgeon, but his development of a non-surgical protocol is not surprising, said Dr. Kenneth Kaushansky, senior vice president for health sciences at SBU and dean of the school of medicine.
"Larry is a terrific hand surgeon. He could have kept operating" on these cases, but he knew the non-surgical method "is better for the patients," said Dr. Kaushansky, calling hand operations for Dupuytren's "major surgeries."
Dr. Kaushansky continued , "Larry and Marie surmised that since these are fibrous bands" that contract the fingers of Dupuytren's sufferers, "why not inject an enzyme that dissolves fibrous bands? Then you open up the hand, and it pops open." Their collaboration is a great example of team-based ingenuity needed in an age of complex medical problems, he said. "No one person anymore can go into a laboratory and come up with a 'eureka' discovery."
Badalamente is partnering with SBU colleague Dr. Edward Wang to find out if Xiaflex can help patients with frozen shoulder. Dr. Wang, associate professor of orthopedics, said they've seen "good preliminary results, a rapid improvement in the condition that would not normally occur." Xiaflex treatment for frozen shoulder is in clinical trials at multiple medical centers, including Stony Brook. Dr. Wang said one of their study patients is a flight attendant who's had a stiff shoulder for two years. "We injected her on a Monday. By Friday, she had almost normal range of motion," he said.
Dr. Wang and Badalamente are monitoring the study subjects' blood and MRI results, to figure out the volume and concentration of Xiaflex needed to treat frozen shoulder safely and effectively. He said they expect to launch a bigger study in the spring, "with more patients and a control group." They hope "to show the world that once again, here is a novel use for the drug."
Badalamente and Dr. Hurst "came up with a new idea, and saw it all the way through" from lab to commercially available treatment for Dupuytren's, Dr. Wang said. "Now it's gained wider acceptance, and patients are demanding it."