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Novel treatment strengthens bones in genetic disease neurofibromatosis type-1
Date:8/14/2014

An enzyme therapy may prevent skeletal abnormalities associated with the genetic disorder neurofibromatosis type-1, Vanderbilt investigators have discovered.

The researchers demonstrated in a mouse model of the disorder that the enzyme asfotase-alpha improves bone growth, mineralization and strength. The findings, reported in the August issue of Nature Medicine, "suggest that we can make bone stronger and better by injecting this drug, and possibly prevent fractures in patients with neurofibromatosis," said Florent Elefteriou, Ph.D., director of the Vanderbilt Center for Bone Biology.

While he is excited about the results, Elefteriou emphasized the challenge of moving from mouse to human studies. "It's very difficult to set up a clinical trial in patients with a rare disease; it will have to be an international effort to pool these patients," he said.

Neurofibromatosis type-1 (NF1) is caused by mutations in the gene for neurofibromin, a protein that regulates cellular signaling pathways. The disorder causes nervous system tumors and skeletal pathologies including scoliosis, bone fragility, fracture and pseudoarthrosis (non-union of the bone following fracture).

Fractures are treated surgically to stabilize the bone and promote healing. Some families opt for amputation, to spare their children the pain of repeated surgeries, Elefteriou said.

"We wondered if there might be a way to prevent the fractures from happening in the first place," he said.

It was difficult to even propose non-surgical preventive treatments, however, because it was unclear how mutations in neurofibromin cause skeletal pathologies.

To investigate the molecular pathology of NF1, Elefteriou and his colleagues, including first author Jean de la Croix Ndong, Ph.D., have studied a mouse model of the disorder. They noticed in histological stains of bone tissue that the mice had an accumulation of non-mineralized matrix, a conditio
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Contact: Leigh MacMillan
leigh.macmillan@vanderbilt.edu
615-322-4747
Vanderbilt University Medical Center
Source:Eurekalert  

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