A study published today in PLOS ONE discovered the origin of severely disfiguring masses of cells, called neurofibromas, that gradually develop throughout the skin of patients afflicted with Neurofibromatosis 1 (NF1). The discovery consisted of micro-lesions that contain small pathological clusters of nerve fibers and associate Schwann cells that proliferate to form the bulk of the disfiguring neurofibromas.

Neurofibromatosis 1 (NF1) afflicts about 1 in 3,000 people throughout the world and is a genetic dominant disorder caused by a mutation in only one of two NF1 genes. Although neurofibromas in the skin can be severely disfiguring, they rarely become cancerous. Therefore, prior to today’s study, research focus on neurofibromas as mysterious benign tumors that can occur simultaneously at multiple sites where aberrant Schwann cell proliferation begins independently.

Instead of a typical cancer relate approach that focus on neurofibromas as benign tumors; so they took a different tactic of investigating why NF1 patients also suffer from chronic pain and itch; hence even in areas of the skin without neurofibromas. These symptoms had receive little attention,” said lead investigator Dr. Rice. “To our surprise; they discover that nerve fiber terminals in the skin were actually a previously unknow source of the neurofibromas.

At the beginning of the study, biopsies from normal appearing; also neurofibroma-free skin were taken from 19 NF1 patients and skin from 16 normal subjects. Biopsies of 17 of the 19 NF1 patients had previously undetected micro-lesions consisting of small, dense clusters of nerve fibers and their associate Schwann cells.

Immuno fluorescence assays

The study then expand to investigate actual neurofibromas; which were collect and donate by the Children’s Tumor Foundation in New York City. Using immuno fluorescence assays develop by Integrate Tissue Dynamics and combine with gene expression analyses develop by Sage Bionetworks in Seattle; so this research confirm that the neurofibromas indeed grew from the micro-lesions.

With an awareness of micro lesions in human NF1 patients; so similar micro lesions were find in mice that had an equivalent genetically engineer mutation; so only in Schwann cells causing some of them to proliferate and form neurofibromas. These mice were develop previously by Nancy Ratner, Ph.D., Program Leader for Cancer Biology and Neural Tumors Program at Cincinnati Children’s.

Base on these results; they believe that the identification of a pre clinical lesion; which could allow for the development of therapies to eliminate neurofibromas or stop new ones from developing,” said Dr. Wymer, now a Professor of Neurology at The University of Florida. This brings hope to thousands of NF1 patients where disfigurement; so cause by these neurofibromas usually begins in their teen years.

Around 2.5 million people worldwide have neurofibromatosis, a genetic disease; so although only half of the initial cases of NF1 in a family (or one-third of all cases) can be link back to a parent; hence NF1 can also occur spontaneously without prior heredity Neurofibromatosis is more prevalent than all cases of cystic fibrosis; so Duchenne muscular dystrophy and Huntington’s disease combined.