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Study targets key molecule to reverse kidney damage in mice
Date:3/7/2012

physiology at Columbia University and immediate past editor of the journal Kidney International. Al-Awqati, who was not involved in the study, notes that kidney disease is the third leading cause of death in the U.S.

In the kidneys and other organs, fibrosis develops from normal repair mechanisms that do not stop. Scar tissue slowly builds up and replaces the working cells of the organ. In 2003, Kalluri's lab reported that the destructive fibrosis in mice can be countered by the human protein BMP-7, originally named for its ability to spur bone growth. A manmade version of BMP-7 is approved by the U.S. Food & Drug Administration (FDA) to help repair long bones and vertebrate disks. However, the large protein needs to be injected or surgically implanted and, therefore, is not useful for long-term treatment protocols.

Kalluri and his colleagues continued their studies, seeking a smaller molecule that could be taken by mouth in a pill form in order to more specifically exert its protective effect on the kidney. Probing deeper into the biology of the kidney, they identified the protein Alk3, which is not the protein's primary partner in bone.

Soon after the BIDMC team identified the key receptor Alk3 in the lab, they collaborated with a Canadian biotechnology company, Thrasos Therapeutics, interested in developing targeted therapies for the prevention and treatment of severe organ failure, especially kidney disease. Based on the details about the molecular interaction between the BMP protein and the ALK receptor, company scientists developed a class of small functional peptides, including THR-123, which then underwent further testing.

Researchers in the Kalluri lab used the experimental compound to document the role of the receptor in reversing the fibrosis and allowing normal tissue to regenerate in one mouse model after another. "This receptor must be present for the new molecule to function," said Kalluri. Working through the rec
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Contact: Bonnie Prescott
bprescot@bidmc.harvard.edu
617-667-7306
Beth Israel Deaconess Medical Center
Source:Eurekalert

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