Some cases of rickets, such as familial hypophosphatemic rickets, have a genetic basis. These cases are often caused by a mutation in the protein PHEX. Boukpessi et al hypothesized that PHEX impairment resulted in the release of a peptide, ASARM, which is known to inhibit dentin mineralization. They observed that ASARM was abnormally produced in patients with familial rickets, and that both symptoms and ASARM production could be attenuated by a diet high in vitamin D and phosphate during growth. The presence of the ASARM peptide may thus contribute to impaired dentin mineralization in rickets, in a manner compensated for by vitamin D and phosphate.

Dr. Chaussain and colleagues suggest that "the release of this peptide may partially explain the impaired dentin mineralization associated with the disease in teeth from hypophosphatemic patients with mutation of the PHEX gene. However, treatment during growth may limit the clinical consequences of this anomaly in the dentin of permanent teeth. This observation highlights the importance of improving phosphate and vitamin D environment on dentin mineralization, which compensates the adverse effect of PHEX mutation."

Boukpessi T, Gaucher C, L-ger T, Salmon B, Le Faouder J, Willig C, Rowe PS, Garab-dian M, Meilhac O, Chaussain C: Abnormal presence of the MEPE-derived ASARM peptide in human hypophosphatemic dentin. Am J Pathol 2010, 177: 803-812

Dr. Pravin C. Singal and colleagues at the Feinstein Institute for Medical Research, Manhasset, NY; the Texas Health Science Center, San Antonio, Texas; and New York Medical College, Valhalla, NY have identified mammalian target of rapamycin (mTOR) as a therapeutic target for HIV-associated nephropathy. These results are presented in the August 2010 issue of the American Journal of Pathology.

HIV-associated nephropathy, or kidney disease that develops in association with HIV infection, usually occurs only with advanced disease. HIV-associated nephropathy may be caused by direct HIV-1 infection in the renal cells, with resulting renal damage through the viral gene products, or by changes in the release of inflammatory molecules during HIV infection.

HIV-associated nephropathy is characterized by cell proliferation in affected kidney lesions. To determine if mTOR, which plays a key role in cell growth, was involved in this proliferative phenotype, Kumar et al examined mTOR activation in a mouse model of the disease. Both mTOR and its downstream targets were activated at higher levels in diseased mice as compared with controls, indicating enhanced activation of the mTOR signaling pathway. In addition, both mTOR activation and renal disease could be blocked by treatment with rapamycin, which inhibits the mTOR pathway. This report therefore supports mTOR as a therapeutic target for HIV-associated nephropathy.

Source: American Journal of Pathology