An experimental drug used in clinical trials for advanced cancer has been found to stop abnormal brain cell growth in mice—a discovery researchers say could help prevent learning disabilities in children with neurofibromatosis 1 (NF1) and similar genetic diseases affecting a cellular signaling pathway.
The finding should lead to additional research on how anti-tumor drugs might protect the developing brains of young children, according to the team of U.S. and Japanese researchers, which published their findings online in the journal Cell.
The team gave mice PD0325901, an MEK inhibitor that blocks tumor growth within the MEK/ERK pathway. Mice with the NF1 gene mutation that received PD0325901 from birth developed normally, while mice not receiving the drug became hunched and scruffy within a few days of birth, due to abnormal body and brain cell growth. In newborn mice with two copies of the NF1 mutation, neural stem cells in the brain were far more likely to produce glia—but far less likely to generate neurons for the brain and body.
Yuan Zhu, Ph.D., the paper’s senior author, cautioned that while PD0325901 may not be suitable as a cancer treatment in children, other MEK inhibitors designed to fight cancer may be found to achieve similar results.
“The important thing is that we have shown that by treating during this brief window of time early in life, when neural stem cells in a developing brain still have time to ‘decide’ what kind of cell to become, we can cause a lasting effect on neural development,” said Dr. Zhu, an associate professor of internal medicine at the University of Michigan Medical School, based at its Division of Molecular Medicine and Genetics, and Department of Cell & Developmental Biology.
In addition to NF1, the researchers predict that their findings may have importance for patients with neuro-cardio-facial-cutaneous syndromes or RASopathies such as Costello, Leguis, Leopard, and Noonan syndromes.
[An abstract of the study, “ERK Inhibition Rescues Defects in Fate Specification of Nf1-Deficient Neural Progenitors and Brain Abnormalities,” can be read at http://www.cell.com/abstract/S0092-8674%2812%2900871-9].