Multicenter Study Advances Fight Against Neurofibromatosis

Multicenter Study Advances Fight Against Neurofibromatosis

Jun 13, 2004 6:00 PM

The fight against neurofibromatosis type 1 - a common, inherited neurocutaneous disorder affecting one in 4,000 people worldwide - got a boost recently with a grant for the design of a multicenter clinical trial on a severe manifestation of the disease. The study is being spearheaded by University of Utah School of Medicine researchers.

The Department of Defense Neurofibromatosis Research Program last month awarded $146,014 toward the development of a study encompassing three clinical trials that will focus on detection and treatment of malignant tumors in neurofibromatosis type 1 (NF1). Worldwide, this form of NF is more prevalent than cystic fibrosis, hereditary muscular dystrophy, Huntington's disease, and Tay Sachs combined. Symptoms include multiple birthmarks (cafe au lait spots) and tumors of the skin (neurofibromas) and peripheral nervous system.

"NF1 patients are at increased risk to develop both benign and malignant tumors, and the most common are those involving the peripheral nerve sheath," said David H. Viskochil, M.D., Ph.D., professor, chief of the U medical school's Division of Pediatric Genetics, and principal investigator for the study's administrative core, which will oversee the clinical trials. Members of the Sarcoma Center at the University of Utah's Huntsman Cancer Institute and researchers from the Informatics Core of the Huntsman Clinical Research Center are also part of the project.

The study will focus on malignant peripheral nerve sheath tumors (MPNST), sarcomas that comprise up to 10 percent of all malignant soft-tissue tumors. NF1 patients are ideal subjects for the study because half of the MPNST population is also diagnosed with NF1.

"Presently there is no effective surveillance protocol for early detection, nor is there effective medical treatment for the management of MPNST," said Viskochil.

The first clinical trial will confirm identifiable risk factors for developing MPNST among NF1 patients. It will compare clinical, genetic, and environmental features between NF1 patients who have MPNST and those who don't.

The second clinical trial will investigate whether PET scanning (positron emission tomography) is effective in diagnosing MPNST without a tissue biopsy.

In the third clinical trial, investigators will test whether neoadjuvant chemotherapy is effective in reducing the size of MPNST prior to surgery.

Primary investigators for the three clinical trials, respectively, are Jan Friedman, University of British Columbia; Rosalie Ferner, Guy's and St. Thomas' Trust; and Brigitte Widemann, National Cancer Institute. The National Neurofibromatosis Foundation will help in recruitment of participants.

Viskochil has longstanding involvement in neurofibromatosis research. In 1990, he was part of a team of investigators from U medical school that identified and cloned the gene that triggers NF1. The dominant inheritance pattern of NF1 means that every child of an NF1 patient has a 50 percent chance of having the disorder. However, the medical manifestations and severity cannot be predicted.

Most NF1 cases are mild to moderate, but in some patients, the disorder can lead to disfigurement, blindness, bone abnormalities, malignancies, and learning disabilities. NF2, the less common form of neurofibromatosis, affects about one in every 40,000 people worldwide. It is characterized by tumors on the eighth cranial nerve, and is a separate genetic disorder.

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