Researchers from Washington University School of Medicine in St. Louis have found that a drug used to treat epilepsy in children can stop or slow down the growth of NF1-linked optic gliomas in mice. This discovery paves the way for a potential clinical trial. NF1 is a genetic condition that leads to the growth of tumors on nerves throughout the body, including the optic nerves that connect the eyes to the brain.The goal of the research is to examine whether the drug lamotrigine can be effective in preventing or delaying brain tumors in children with NF1. The findings of the study have been published in the journal Neuro-Oncology.
Senior author, David H. Gutmann, MD, PhD, who holds the Donald O. Schnuck Family Professor of Neurology and directs Washington University’s Neurofibromatosis Center, stated, “Based on these data, the Neurofibromatosis Clinical Trials Consortium is considering launching a first-of-its-kind prevention trial.” The consortium, formed in 2006 by the U.S. Department of Defense, is an international network of NF scientists working to find therapies for the condition.The plan is to enroll children who do not show any symptoms of neurofibromatosis, provide them with treatment for a limited period, and then observe whether there is a decrease in the number of children who develop tumors requiring treatment. This innovative approach was presented to a neurofibromatosis focus group, and the response was positive. Patients with NF1 expressed their approval of a short-term treatment with a drug that has been safely used for 30 years, as long as it reduced the risk of their children developing tumors that would necessitate chemotherapy with potential side effects. The most severe tumors affecting individuals with NF1 impact the eye.optic nerve tumors, also known as optic gliomas, often occur in children between the ages of 3 and 7. Although these tumors are not usually deadly, they can cause vision loss in around one-third of patients, along with other symptoms such as early puberty. The standard chemotherapy used to treat optic gliomas is only moderately successful at preventing further vision loss and can also have an impact on the developing brains of children, leading to cognitive and behavioral issues.
In a previous research study, Gutmann and Corina Anastasaki, PhD, discovered that lamotrigine was able to stop the growth of optic gliomas in NF1 mice by inhibiting neuronal hyperactivity. The Neurofibromatosis Clinical Trial Consortium was interested in the data but required additional evidence before considering a clinical trial. They requested Gutmann and Anastasaki to clarify the connection between Nf1 mutation, neuronal excitability, and optic gliomas; determine the effectiveness of lamotrigine at safe doses for children with epilepsy; and conduct these studies in multiple strains of NF1 mice.
NF1 is a highly variable disease in humans and can be caused by thousands of different mutations in the NF1 gene, each of which could be associated with different outcomes.
Associated with various medical conditions. Conducting experiments on multiple breeds of mice was a way to determine whether lamotrigine was effective in humans regardless of the specific mutation.
Anastasaki and Gutmann not only demonstrated the effectiveness of lamotrigine in two strains of NF1 mice, but also found that the drug worked at lower doses than those typically used for epilepsy, suggesting it was likely safe. Furthermore, they discovered that a short course of the drug had long-lasting effects, both as a preventative measure and as a treatment. Mice with tumors that were treated for four weeks beginning at 12 weeks of age saw their tumors stop growing .
Research showed that the drug did not cause any additional damage to the retinas of the mice’s eyes. In fact, mice that were given the drug for four weeks starting at 4 weeks old, which is before tumors usually appear, did not experience any tumor growth even four months after the treatment was stopped.
Gutmann’s findings suggest that a one-year treatment course for young children with NF1, possibly between the ages of 2 to 4, could potentially decrease their risk of brain tumors.
Gutmann expressed excitement about the possibility of changing the outlook for these children by intervening during a short time frame. He emphasized the importance of getting them past the age when these tumors typically develop.The author expressed her hope that if children with NF1 can be accurately identified earlier in life, they may not ever require treatment once they reach the age of 7. The author also mentioned her desire to avoid discussing chemotherapy for children who are too young to be in first grade.
