Recent Advances in Neurofibromatosis

Written by Denise Mann
Medically Reviewed by Christopher Melinosky, MD on October 21, 2025
6 min read

About 1 in every 2,000 babies is born with the genetic disease neurofibromatosis (NF).

Until recently, little information existed about how this disease happens. There were even fewer treatment options, none of which was specifically approved to treat any of NF's often disabling symptoms.

Now, thanks to grassroots efforts from families affected by NF, new treatments have been identified. And the pipeline of new NF treatments is full. There are three times as many new drug trials in NF today as there were just 10 years ago. 

NF is the umbrella name for genetic conditions that cause tumors to grow throughout your body. They can appear anywhere and affect every person differently. Neurofibromatosis type 1 (NF1) makes up about 96% of all NF.  It's the form of the condition that has had the most treatment advances so far.

"We are in the midst of a watershed moment," says Jaishri Blakeley, MD, director of the Neurofibromatosis Therapeutic Acceleration Program at the Johns Hopkins University Comprehensive Neurofibromatosis Clinic in Baltimore. "The years of discovery efforts related to NF1 have yielded an immense amount of data and understanding, and this is now being paired with new drugs and therapeutic opportunities developing across the scientific landscape."

 

Much of the recent treatment advances in NF are aimed at the soft tumors on or around nerves (plexiform neurofibromas). When the NF1 gene is faulty, it doesn't make neurofibromin – a protein that acts as a brake to stop tumors from forming. When the brake is not working properly, neurofibromas grow unchecked. This understanding paved the way for the FDA's approval of two new treatments for these tumors in NF1.

Their target? The mitogen‐activated protein kinase kinase (MEK). 

MEK is part of a signaling pathway that overreacts in people with NF1. It lays the groundwork for the NF1 gene to stop working. MEK inhibitors block MEK and shrink the tumors on or around the nerves. The MEK inhibitor selumetinib (Koselugo) was approved in 2020 for children with NF1 and plexiform neurofibromas. A second MEK inhibitor, mirdametinib (Gomekli), was approved for kids and adults with NF1 and plexiform neurofibromas in 2025. 

These drugs can make a huge difference in quality of life, says R. Taylor Sundby, MD, a pediatric hematologist-oncologist and researcher at Nemours Children's Hospital in Wilmington, Delaware. "These drugs can cause a 20% to 30% decrease in tumors," he says. "If something is near your arm, that might mean all of a sudden, you have full mobility, whereas previously, you just had limited mobility."

Some people do better on one than the other, Blakeley says. And these drugs do have their share of side effects, including rashes, nail infections, stomach pain, and fatigue. These are the reasons why more NF1 treatments are needed, she says.

This drug targets the area around the nerve tumors in NF1. It was discovered using artificial intelligence and machine learning. The FDA gave HLX-1502 special statuses – Fast Track, Orphan Drug, and Rare Pediatric Disease. This would streamline the process and hopefully bring it to patients sooner. "The cells next to the tumor cells really affect how they behave and how they respond to different treatments," Sundby says.

MEK inhibitors block the pathway for both healthy and tumor cells, which could cause side effects. But HLX-1502 targets only the surrounding cells that support the tumor growth, leaving the others alone. The hope is that it will have the same benefits, with fewer side effects. 

Research is looking at pairing the MEK inhibitor selumetinib with cabozantinib (Cabometyx, Cometriq), a tyrosine kinase inhibitor (TKI) to see whether these drugs work better together. The protein pathway RAS/MAPK is the major one involved in NF1. When it is faulty, it affects downstream pathways including MEK and other kinases such as tyrosine kinase. "The more exits you are able to close, the better control you will have," Sundby says.

People with NF1 get flesh-colored, pink, or tan bumps on or under their skin called cutaneous neurofibromas. These will never become cancer but can damage the appearance of your skin and make you feel self-conscious. Some people may have just a few bumps, while others can have hundreds or even thousands all over their body. NFX-179 is a MEK inhibitor gel that is applied to the skin. It's in a clinical trial. Other MEK inhibitors do work on these tumors, but they come with side effects. The hope is that a gel can spot-treat these skin tumors with fewer side effects. 

Dermatologists are also working on combining lasers and other energy-based devices with fat-melting injectables to help shrink these tumors without surgery.

About 10% of people with NF1 who have nerve tumors may get a cancer called malignant peripheral nerve sheath tumor (MPNST). There is no way of knowing which nerve tumors will go on to become cancer, Sundby explains. "How do you know which one to biopsy? It's also a lifelong disease, and we don't want to do a biopsy every year," he says. "These tumors grow on or near nerves, so there's always the risk of doing harm during a biopsy."

As of now, these cancers are picked up once they have started to spread and are less likely to respond to treatment. But catching them earlier through blood tests and smart imaging may give people a life-saving head start. There are markers floating around in the blood (cell-free DNA) that can help doctors know who is more likely to get a cancer. "The hope is that we will identify these markers, and then patients can get a blood draw at a local lab, which means less time off work and is a big thing for people with these lifelong diseases," Sundby says. If someone is high-risk, regular imaging exams can help catch the cancer early.

Other MEK inhibitors are being tested on other NF1 symptoms. "Early research suggests that MEK inhibitors have activity in preventing bone disease like scoliosis, and can improve aspects of cognitive and behavioral function," Blakeley says.

While much of the progress so far has been in NF1, there have been wins in other forms of the disease, such as neurofibromatosis type 2 (NF2)-related schwannomatosis. A drug already approved to treat lung cancer, brigatinib (Alunbrig), may shrink tumors called vestibular schwannomas on the nerve. These tumors can cause hearing loss. In one very small study of 40 patients, 10% of growing tumors and 23% of all tumors shrank, and about one-third of people in the study had improvements in their hearing and less pain.

Some kids who have NF1 have learning issues. "If you notice café-au-lait spots on your child, talk to your pediatrician about getting care at an NF center that will have the latest resources," Sundby says.

Teams there can tell you what to watch for. "Even if your loved one has very mild manifestations, an expert center can provide surveillance guidance and make families aware of new developments and new clinical opportunities," Blakeley says. 

Find NF centers via patient advocacy groups though the Children's Tumor Foundation NF Clinic Network (NFCN).