This new evidence has researchers wondering if anti-tumor drugs could possibly protect kid's brain who have neurofibromatosis 1 and other learning disabilities during the key developmental stage.
Neurofibromatosis 1 (NF1) is present in 1 in every 3,000 kids. This disease causes tumors to grow all over the children's bodies, and sometimes results in abnormally large heads, as well as other health problems. Children affected by NF1 have a hard time writing, solving math problems, reading, and behaving appropriately.
Brown marks on skin appear early on if NF1 is present, and doctors often mistake them for birthmarks. The influence on healthy brain function is the most serious problem associated with NF1, and is usually prevalent soon after the brown marks appear. The authors note that the actual impact that NF1 has on brain function is still unknown, regardless of the fact that multiple studies have been done on the tumors that pop up later in the patient's life.
For their new study, the University of Michigan Medical School researchers analyzed neural stem cells. These are master cells which can transform into different types of neural tissue.
They discovered that the baby mice that had 2 copies of the mutation that results in NF1, had neural stem cells which produced more nerve cells called glia, and did not produce enough neurons - important for the brain and body to communicate with one another.
These mice were treated with a drug called PD0325901, an experimental drug which has been used in trials for treating advanced cancer. This medication targets the actions of cells named MEK/ERK pathway, part of the class of MEK inhibitor drugs.
The scientists found a large difference between the mice with the NF1 mutation that received the medication right from birth - with those mice forming normal brain development. On the other hand, the mice who did not seem to be "normal" when they were first born, but it was noticeable in a couple of days that they were developing abnormally. They were bent over and "scruffy".
Lead author of the research and an associate professor of internal medicine in the Division of Molecular Medicine and Genetics and in the Department of Cell & Developmental Biology, Yuan Zhu, Ph.D notes that not all children who have been diagnosed with NF1 will benefit from this specific drug, however, other MEK inhibitors are in the process of being made to fight against cancer.
"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."
The experiment did not involve the scientists analyzing how the mice behaved, learned or what their chances were of developing the benign brain tumors that often come with NF1.
The best way for the drug to work, according to Zhu, is to administer it at the first sign of benign tumors or delay in development, and after toddlers or infants are diagnosed with NF1.
Around 50% of cases of NF1 are due to genetics, where parents have passed down the mutation to their offspring. The other half of NF1 cases develop in the womb by an unknown cause.
Every case of this disease is different. One child might, with parents who have NF1, have very mild symptoms, while at the same time, their brother or sister is struggling with harsh symptoms.
Another form of NF1 is when a "double hit" occurs. These people have 2 copies of the mutated gene in their cells. If an individual has these 2 copies, they tend to suffer from severe learning symptoms and usually have a larger corpus callosum, the part of the body that joins the two halves of the brain and is home to many glia cells, the cells which the mice had many of.
The recent findings make the scientists hopeful that they can use this information to someday help individuals who have genetic problems similar to NF1 and affect the same cell-signaling pathway named RAS. These types of genetic conditions, called "RASopathies" or neuro-cardio-facial-cutaneous (NCFC) syndromes, include Leguis syndrome, Leopard syndrome, Noonan syndrome and Costello syndrome. They are similar to NF1 because they target the face, head, circulation system, and brain.
The gene for NF1 was found late in the 1980s by U-M Medical School faculty member Francis Collins, M.D., Ph.D., and because of his discovery, children with NF1 can be diagnosed effectively and be treated accordingly.
Written by Christine Kearney