Global Health Nexus, Winter 2004

Phase I Drug Study to Treat Rare Dermatological Disorder Underway

NYU College of Dentistry’s Bluestone Center for Clinical Research is one of four sites — and the only dental school — to participate in a Phase I study involving oral manifestations of a dermatological disorder. The other sites participating in the study are Johns Hopkins School of Medicine, Case Western Reserve School of Medicine, and the University of California at San Francisco (UCSF) School of Medicine.

The new study will assess an investigational drug therapy for Pemphigus Vulgaris, a dermatological disorder, which causes burn-like lesions or blisters to develop on the skin and mucous membranes, including in the mouth. NYU will enroll one-fifth of the trial’s subjects. The two-year trial is sponsored by biotechnology developer Peptimmune, Inc.

Classified as a rare disorder by the FDA, Pemphigus Vulgaris causes the body to produce an immune response to a specific portion of desmoglein 3, a protein found in normal healthy skin and oral mucosa. This results in painful eruptions on the face and neck or in the mouth, which, if left untreated, can lead to disfigurement and even death.

“Most Pemphigus Vulgaris patients experience oral lesions,” says Dr. Jonathan Ship, Director of the Bluestone Center for Clinical Research, and a coinvestigator in the trial.

“One of the advantages of this project is that we’ve been able to overcome traditional obstacles to dentist- physician collaboration, thanks to having a research facility designed specifically for studies involving both medical and oral health components. The Bluestone Center enables physician-dentist involvement in both the development and implementation of a research protocol,” said Dr. Ship.

The Pemphigus trial evaluates the safety of PI0824, a tolerizing peptide that is intended to desensitize the immune system by targeting and disabling defective T cells before they can start an abnormal immune reaction against healthy skin and oral mucosal cells. The treatment has the potential to relieve symptoms without the serious side effects associated with corticosteroids and immunosuppressants, which are commonly prescribed for Pemphigus treatment. Subjects in the Peptimunne study continue to receive daily corticosteroid therapy.

Dermatologic medications are commonly used off-label to treat some two dozen oral mucosal conditions, such as chronic canker sores (aphthous stomatitis) and lesions caused by candida (fungal) infections, Dr. Ship said. But drug-makers have been reluctant to sponsor research to support applications for oral indications in part because of a shortage of clinical research facilities that can efficiently carry out studies requiring oversight by both dentists and dermatologists.

He noted that the Pemphigus trial involves systemic drug administration via infusion requiring close medical supervision throughout the day, as well as dermatology and oral medicine expertise in assessing Pemphigus- associated lesions. The Bluestone Center’s research nurses are using US Holter’s new digital ECG continuous monitoring system for this study.