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Improving Outcomes for Patients with NF1

When 9-year-old Philip Moss ran out of treatment options for his neurofibroma tumors in April 2015, his doctors directed his family to NCI. NCI was leading the only treatment trial in the nation for children with tumors caused by neurofibromatosis type 1 (NF1), a genetic disorder in which painful and often disfiguring tumors of the nerves can grow on or under the skin. These tumors are generally benign, but about 10% of people with NF1 will develop a cancerous neurofibroma. There are currently no Food and Drug Administration-approved therapies for NF1.

Philip’s experience with NF1 began when he was 6 years old, with the detection, diagnosis, and removal of a tumor on his neck. “We’d never heard of NF1 before; our world changed,” said Renie Moss, Philip’s mother. Unfortunately, the tumor regrew over the next few years. After additional surgery, routine imaging scans revealed that the tumor was growing again, and, over a 6-month period, it grew from the size of a ping pong ball to the size of a tennis ball. In addition, other tumors had developed. The tumor on his neck was particularly concerning because it could obstruct his airway or cause other complications. “We felt like we were one step away from disaster,” recalled Renie.

Philip’s doctor referred them to a phase I clinical trial at the NIH Clinical Center in Bethesda, Maryland, that was testing an experimental targeted therapy called selumetinib. The trial was led by Brigitte Widemann, M.D., chief of NCI’s Pediatric Oncology Branch, and involved collaborators from Children’s Hospital of Philadelphia, Cincinnati Children’s Hospital Medical Center, and the Children’s National Health System.

Laboratory researchers had previously shown that mutations in the NF1 gene cause neurofibromas to grow through a chemical pathway inside cells called the RAS pathway. Selumetinib blocks a specific node in this pathway called MEK. In mouse models of NF1, MEK inhibitors reduced the growth of neurofibroma tumors. Other MEK inhibitors are safe and effective in other types of adult cancers. Based on these findings, researchers hypothesized that selumetinib might work in NF1 tumors in children.

In September 2015, Philip visited NCI for an intense medical evaluation, joined the trial, and began taking selumetinib twice a day. Because the drug is provided in pill form, Philip was able to return home for ongoing treatment and was monitored by his local pediatrician. He and his family learned to cope with the initial side effects of treatment, which included fatigue, headaches, and nausea. One year after joining the trial, Philip’s tumors were 36% smaller.

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Although this trial was a small early-phase study, Philip was among the 71% of children whose tumor volumes decreased by more than 20%. “We saw tumor shrinkage in nearly every patient,” Brigitte remarked. “The shrinkage was measurable…something we had never seen before” among NF1 patients. These promising results are now being pursued in a phase II study.

Philip remains in the trial, and the tumor on his neck has shrunk by half. “Kids don’t ask what’s wrong with him anymore,” said Renie. “It’s meant the world to him and to our family.” Renie acknowledged the years of research that led to this trial. “Someone was planting the seeds in NF1 research so we would benefit from that work now.”

  • Posted: September 21, 2017

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Nf1 seeds

NF1

Lineage: Northern Lights x Chemdawg

Description: NF1 is a hybrid with some very well-known parents—Northern Lights and Chemdawg. This strain brings together the piney scent of Northern Lights with the diesel aroma of Chemdawg. This cultivar offers long lasting physical relaxation with some mental uplift.

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Neurofibromatosis type 1

Neurofibromatosis type 1 is a condition characterized by changes in skin coloring (pigmentation) and the growth of tumors along nerves in the skin, brain, and other parts of the body. The signs and symptoms of this condition vary widely among affected people.

Beginning in early childhood, almost all people with neurofibromatosis type 1 have multiple café-au-lait spots , which are flat patches on the skin that are darker than the surrounding area. These spots increase in size and number as the individual grows older. Freckles in the underarms and groin typically develop later in childhood.

Most adults with neurofibromatosis type 1 develop neurofibromas, which are noncancerous (benign) tumors that are usually located on or just under the skin. These tumors may also occur in nerves near the spinal cord or along nerves elsewhere in the body. Some people with neurofibromatosis type 1 develop cancerous tumors that grow along nerves. These tumors, which usually develop in adolescence or adulthood, are called malignant peripheral nerve sheath tumors. People with neurofibromatosis type 1 also have an increased risk of developing other cancers, including brain tumors and cancer of blood-forming tissue (leukemia ).

During childhood, benign growths called Lisch nodules often appear in the colored part of the eye (the iris). Lisch nodules do not interfere with vision. Some affected individuals also develop tumors that grow along the nerve leading from the eye to the brain (the optic nerve ). These tumors, which are called optic gliomas, may lead to reduced vision or total vision loss. In some cases, optic gliomas have no effect on vision.

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Additional signs and symptoms of neurofibromatosis type 1 vary, but they can include high blood pressure (hypertension), short stature, an unusually large head (macrocephaly ), and skeletal abnormalities such as an abnormal curvature of the spine (scoliosis ). Although most people with neurofibromatosis type 1 have normal intelligence, learning disabilities and attention-deficit/hyperactivity disorder (ADHD) occur frequently in affected individuals.

Frequency

Neurofibromatosis type 1 occurs in 1 in 3,000 to 4,000 people worldwide.

Causes

Mutations in the NF1 gene cause neurofibromatosis type 1. The NF1 gene provides instructions for making a protein called neurofibromin. This protein is produced in many cells, including nerve cells and specialized cells surrounding nerves (oligodendrocytes and Schwann cells). Neurofibromin acts as a tumor suppressor, which means that it keeps cells from growing and dividing too rapidly or in an uncontrolled way. Mutations in the NF1 gene lead to the production of a nonfunctional version of neurofibromin that cannot regulate cell growth and division. As a result, tumors such as neurofibromas can form along nerves throughout the body. It is unclear how mutations in the NF1 gene lead to the other features of neurofibromatosis type 1, such as café-au-lait spots and learning disabilities.

Learn more about the gene associated with Neurofibromatosis type 1

Inheritance

Neurofibromatosis type 1 is considered to have an autosomal dominant pattern of inheritance. People with this condition are born with one mutated copy of the NF1 gene in each cell. In about half of cases, the altered gene is inherited from an affected parent . The remaining cases result from new mutations in the NF1 gene and occur in people with no history of the disorder in their family.

Unlike most other autosomal dominant conditions, in which one altered copy of a gene in each cell is sufficient to cause the disorder, two copies of the NF1 gene must be altered to trigger tumor formation in neurofibromatosis type 1. A mutation in the second copy of the NF1 gene occurs during a person’s lifetime in specialized cells surrounding nerves. Almost everyone who is born with one NF1 mutation acquires a second mutation in many cells and develops the tumors characteristic of neurofibromatosis type 1.