Japanese firm, IU unite for research on gene discovered at IU

Gene responsible for ADHR may lead to therapeutics for kidney, bone diseases

By Mary Hardin

The gene, isolated in 2000, on the short arm of chromosome 12 is responsible for autosomal dominant hypophosphataemic rickets (ADHR), a rare disorder only known to exist in a handful of families worldwide. Only about 30 people in the United States are known to suffer from the rare, inherited form of rickets, which can cause leg deformity, tooth abscesses, bone pain and fractures. The kidneys of individuals with the FGF-23 mutation cannot retain phosphorus, an important element for maintaining bone integrity.

“Research into this very rare disease may lead to potential therapeutics for a very common disease,” said Dr. Michael Econs, professor of medicine and of medical and molecular genetics at the IU School of Medicine (IUSM). Econs, along with Kenneth E. White, assistant professor in the IU Department of Medicine, made the discovery of FGF-23 in collaboration with the German laboratory of Dr. Tim M. Strom.

Researchers at Kirin’s Pharmaceutical Research Laboratories independently identified FGF-23 as a causative factor of tumor-induced osteomalacia, an adult form of rickets. It exhibits some similar symptoms to ADHR such as renal phosphate wasting.

“This license makes our patent position strong with our original invention related to the FGF-23 protein,” said Toshifumi Mikayama, general manager of Kirin’s Pharmaceutical Research Laboratories. “FGF-23 will give us important clues to elucidate the mechanisms of phosphate regulation in the human body and we believe, based on the discovery, we will be able to bring therapeutic benefits to patients suffering from kidney or bone diseases.”

Researchers were excited about the identification of FGF-23 not only from the standpoint that it helps a small number of ADHR patients, but also because it may lead to therapies for individuals with more common diseases such as moderate renal insufficiency. Due to decreased kidney function, patients with renal insufficiency retain excessive amount of phosphorus, which is detrimental to their bones and vessels.

Kirin researchers have developed a test to measure FGF-23 concentrations in the blood. They are developing a commercially available test that can be used for future research and diagnostic endeavors involving a range of disorders that potentially involve FGF-23.

Funding for the original research came from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, part of the National Institutes of Health. IU’s Advanced Research and Technology Institute handled the arrangements.