Potential therapy discovered for hypophosphatasia, a congenital form of rickets

Using a mouse model, José Luis Millán, Ph.D. tested the hypothesis that, when administered from birth, a bone-targeted form of the TNAP gene would ease the skeletal defects of HPP. The Millán laboratory, in collaboration with scientists from Enobia Pharma in Montreal, Canada and from the Shriners Hospitals for Children in St. Louis, Missouri, created a soluble form of human TNAP that had been shown to display a strong attraction to bone tissue. Upon injecting the enzyme into the fat layer under the skin of the mice, the treated mice maintained a healthy rate of growth and apparent well being, as well as normal bone mineral density (BMD) of the skull, femur and spine. In fact, complete preservation of skeletal and dental structures were observed after 15 days, and bone lesions were still not seen after 52 days of treatment.

"While the biochemical mechanism that leads to skeletal and dental defects of HPP is now generally understood," said Dr. Millán, "there is currently no established medical treatment."

Given the success of this therapy in preventing HPP, current efforts in Dr. Millán's laboratory are focused on reversing the bone defects in mice once the disease is quite advanced. Future clinical trials may reveal this as the first promising therapy for patients with this genetic disorder.

This study, published in the Journal of Bone and Mineral Research, was supported by grants from the National Institutes of Health, Enobia Pharma, Inc., and the Shriners Hospitals for Children.

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