Neurofibromatosis and The Children’s Tumor Foundation

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The annual Children’s Tumor Foundation NF Conference was held in Park City, Utah earlier this week (June 10 — 12). For three days, research and clinical investigators from around the world met to present their data and discuss the latest findings in neurofibromatosis (NF) research (pronounced noor-oh-fahy-broh-muh-toh-sis). This year the meeting focused on models, mechanisms and therapeutic targets.

The Children’s Tumor Foundation is dedicated to ending NF through research. The Foundation has sponsored research for over 25 years to understand the molecular basis of NF and to establish effective treatments and improve the lives of those living with the disease.

What is neurofibromatosis (NF)?

NF is usually inherited as an autosomal dominant genetic disorder of the nervous system that causes clinically benign tumors to form on peripheral and optic nerves. However, 30-50% of NF cases arise as a result of a spontaneous genetic change. Tumors that develop in individuals with NF can cause disfigurement, deafness, blindness, bone deformation, learning disabilities and death. NF is the most common neurological disorder caused by a single gene and affects more than 100,000 Americans, making it more prevalent than cystic fibrosis, hereditary muscular dystrophy, Huntington’s disease and Tay-Sachs disease combined [1].

There are two genetically distinct forms of NF: type 1 (NF1), also known as von Recklinghausen NF, which occurs in 1:3,500 births and type 2 (NF2), also known as bilateral acoustic NF, which is rarer than NF1, occurring in 1:25,000 births. A third distinct type of NF, schwannomatosis, has only recently been recognized and affects 1:40,000 individuals. Both NF1 (neurofibromin 1) and NF2 (neurofibromin 2) genes are tumor suppressors.

Symptoms of NF often appear at birth and usually by 10 years of age. Cutaneous neurofibromas (meaning tumors that develop on or just under the skin) typically start to develop around puberty and the number of these tumors increase with age. Although approximately 95% of type 1 neurofibromas are clinically benign, patients often require surgical removal because of disfigurement or disability [2]. However, depending on tumor location, surgery may not be an option and currently, there are no successful molecular therapies.

The most common tumor in individuals with NF1 is the benign peripheral nerve sheath tumor or neurofibroma. In 5-10% of children, a subtype of benign neurofibroma, plexiform neurofibroma, can undergo malignant transformation and become a malignant peripheral nerve sheath tumor (MPNST), a highly aggressive cancer with poor survival [2]. In addition, 15-20% of children with NF1 develop low-grade astrocytomas, typically involving the optic pathway, which may result in vision loss or abnormal endocrine function if they invade the hypothalamus [3].

Clinical advances in NF are being propelled by two recent initiatives:

• NF clinical drug trials are being conducted by a new consortium of ten major teaching hospitals called the NF Clinical Trials Consortium and holds the promise of accelerated drug development.
• The Children’s Tumor Foundation NF Clinic Network, established as a pilot program of four clinics in 2006, is now being rolled out nationwide to provide optimal care at the local level. Components of the network include standards of treatment, clinic operating guidelines and a patient database. Future plans include a centralized tissue repository to facilitate the identification of NF biomarkers and to help identify new drug targets.

Despite these advances, federal funding for research and clinical trials for NF has decreased sharply and is facing the threat of greater cutbacks. The Congressionally Directed Medical Research Program’s NF Research Program has decreased 2.5-fold over the last two years from $25 million in 2005 to $10 million in 2007 [4].

I encourage readers to visit the Children’s Tumor Foundation and consider a gift donation to make a difference in the lives of those affected by NF.

References

1. Facts & Statistics. Children’s Tumor Foundation.
2. Friedman and Birch. Type 1 neurofibromatosis: a descriptive analysis of the disorder in 1,728 patients. Am J Med Genet. 1997 May 16;70(2):138-43.
   View abstract
3. Arun and Gutmann. Recent advances in neurofibromatosis type 1. Curr Opin Neurol. 2004 Apr;17(2):101-5.
   View abstract
4. On the cusp of major clinical advancements, funding for neurofibromatosis research may dry up. Children’s Tumor Foundation press release. 2007 Apr 23.