Approved cancer drug may reduce kidney damage linked to nail-patella syndrome
Researchers led by Dr. Ralph Witzgall, a professor at the Chair of Molecular and Cellular Anatomy at the University of Regensburg, have deciphered a key disease mechanism underlying the hereditary kidney disorder nail-patella syndrome and identified a potential therapeutic strategy. Their findings demonstrate that an already approved drug can significantly reduce disease-causing changes. The…
Researchers from the University of Regensburg and the Technical University of Munich have discovered a potential treatment for a rare kidney disorder called nail-patella syndrome. This inherited condition, characterized by abnormalities in fingernails and kneecaps, primarily affects kidney function and can lead to kidney failure in severe cases.
The study, published in Nature Communications, reveals that certain mutations in the LMX1B gene, responsible for the syndrome, cause kidney damage by disrupting the stability of the LMX1B protein. Normally, LMX1B regulates a genetic program essential for podocytes, specialized kidney cells responsible for filtering blood. When zinc binds to LMX1B, it maintains its structure and function.
However, mutations preventing zinc binding cause LMX1B to become unstable and unstable LMX1B is quickly degraded by the proteasome, a cell's protein-cleaning system.
This degradation leads to a drop in LMX1B levels in podocytes, causing the kidney filtration barrier to form incorrectly and protein to leak into the urine, a key indicator of kidney damage. The researchers found that bortezomib, a cancer drug already approved for use, can stabilize the mutated LMX1B protein, reducing proteinuria (protein leakage in urine) and stabilizing kidney function in mouse models of the disease.
While these findings do not yet translate into immediate treatments for patients, they mark an important step forward. The research suggests that stabilizing mutated LMX1B protein could prevent or at least mitigate kidney damage in nail-patella syndrome. However, the clinical potential of this approach still needs to be established.
Written by urgent.news from Medical Xpress's reporting — not their text. Machine-written — may contain errors; check the original before relying on it.
