NEW YORK (Reuters Health) - A rapamycin analog and interferon gamma both reduce the severity of kidney disease in a mouse model of tuberous sclerosis complex (TSC), a new study shows.
There is currently no treatment for TSC or a related disorder, sporadic lymphangioleiomyomatosis (LAM), Dr. Sandra L. Dabora of Brigham and Women’s Hospital in Boston note in their report in the March issue of Genes, Chromosomes & Cancer.
TSC is caused by mutations in the TSC1 or TSC2 genes that result in increased activity of the mammalian target of rapamycin (mTOR) kinase. Also, increased interferon gamma has been tied to decreased TSC severity in both humans and mouse models of the disease.
The researchers conducted the current study to test the effectiveness of the rapamycin analog CCI-779, which inhibits mTOR kinase activity, and interferon gamma in kidney cystadenomas in mice. They measured severity of kidney disease by necropsy, quantitative histopathology and MR imaging.
CCI-779 reduced the number of cystadenomas per kidney by 62% to 92%, depending on which method was used for measurement, while interferon reduced kidney tumors by 43% to 67%. A similar reduction was seen in liver hemangiomas. Neither drug produced significant toxicity.
The findings, Dr. Dabora and her colleagues write, have “direct relevance for the treatment of kidney angiomyolipomas in TSC and LAM patients.” The researchers are now planning a multi-center trial to evaluate rapamycin for the treatment of kidney angiomyolipomas in TSC or LAM, supported by the National Institutes of Health and the Tuberous Sclerosis Alliance.
In an e-mail interview with Reuters Health, Dr. Dabora said it is crucial for doctors treating patients with TSC or LAM to be aware that clinical trials based on these findings are being planned. “Because these disorders are not common, it is important to encourage participation in clinical trials because this offers the best hope for ultimately improving treatment options for patients with TSC and LAM,” Dr. Dabora said.
The Tuberous Sclerosis Alliance (www.tsalliance.org) and LAM Foundation (www.lam.uc.edu) are good sources of information on these clinical trials, she added.
Source: Genes Chromosomes Cancer 2005;42:213-227. [ Google search on this article ]
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