NIH scientists target bad cellular housekeepers in spectrum of rare disorders

Scientists are learning about common genetic threads that link families of rare diseases for which there are no approved drugs, providing potential paths toward new treatments for the disorders. Now NIH researchers and their colleagues have found one such genetic linchpin behind a rare childhood disease that causes inflammation and fat loss.

The disease name is a mouthful--chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE)--but its long handle covers multiple related diseases. Yet a common link to in all but one child involved in a study was a mutation of the PSMB8 gene, which helps form part of the cellular housekeeper called the proteasome that takes out the protein trash from cells.

"When the proteasome doesn't function, there is a buildup of protein waste products in the cells--much like if your trash wasn't picked up each week, it would accumulate in your driveway," Dr. Raphaela Goldbach-Mansky, a rheumatologist in the NIH's National Institute of Arthritis and Musculoskeletal and Skin Diseases, said in a statement.

Also, high levels of an inflammatory chemical dubbed gamma-induced protein 10 (IP-10) were detected in blood tests, and constitute another finding that helps describe the disorders. Treatment for the diseases is now limited, and doctors often use steroids that fail to treat the root cause of the disease. But that could change. As the findings of the study, which involved collaborators from the U.S., Europe and Israel, could lead to new therapies that address the underlying causes of the spectrum of diseases.

- here's the release

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