Congressional Testimony
Below you will find Senate testimony submitted for the record on behalf of the Neurofibromatosis Network for FY2013.
The Neurofibromatosis Network
Senate Appropriations Subcommittee on Labor, Health and Human Services, Education
Department of Health and Human Services, National Institutes of Health
Thank you for the opportunity to submit testimony to the Subcommittee on the importance of continued funding at the National Institutes of Health (NIH) for research on Neurofibromatosis (NF), a genetic disorder closely linked too many common diseases widespread among the American population.
On behalf of the Neurofibromatosis (NF) Network, a national coalition of NF advocacy groups, I speak on behalf of the 100,000 Americans who suffer from NF as well as approximately 175 million Americans who suffer from diseases and conditions linked to NF such as cancer, brain tumors, heart disease, memory loss, and learning disabilities. Thanks in large measure to this Subcommittee’s strong support, scientists have made enormous progress since the discovery of the NF1 gene in 1990 resulting in clinical trials now being undertaken at NIH with broad implications for the general population.
NF is a genetic disorder involving the uncontrolled growth of tumors along the nervous system which can result in terrible disfigurement, deformity, deafness, blindness, brain tumors, cancer, and even death. In addition, approximately one-half of children with NF suffer from learning disabilities. NF is the most common neurological disorder caused by a single gene and three times more common than Muscular Dystrophy and Cystic Fibrosis combined. There are three types of NF: NF1, which is more common, NF2, which primarily involves tumors causing deafness and balance problems, and schwannomatosis, the hallmark of which is severe pain.
While not all NF patients suffer from the most severe symptoms, all NF patients and their families live with the uncertainty of not knowing whether they will be seriously affected because NF is a highly variable and progressive disease.
Researchers have determined that NF is closely linked to cancer, heart disease, learning disabilities, memory loss, brain tumors, and other disorders including deafness, blindness and orthopedic disorders, primarily because NF regulates important pathways common to these disorders such as the RAS, cAMP and PAK pathways. Research on NF therefore stands to benefit millions of Americans:
Cancer – NF is closely linked to many of the most common forms of human cancer, affecting approximately 65 million Americans. In fact, NF shares these pathways with 70% of human cancers. Research has demonstrated that NF’s tumor suppressor protein, neurofibromin, inhibits RAS, one of the major malignancy causing growth proteins involved in 30 percent of all cancer. Accordingly, advances in NF research may well lead to treatments and cures not only for NF patients, but for all those who suffer from cancer and tumor-related disorders. Similar studies have also linked epidermal growth factor receptor (EGF-R) to malignant peripheral nerve sheath tumors (MPNSTs), a form of cancer which disproportionately strikes NF patients.
Heart disease – Researchers have demonstrated that mice completely lacking in NF1 have congenital heart disease that involves the endocardial cushions which form in the valves of the heart. This is because the same ras involved in cancer also causes heart valves to close. Neurofibromin, the protein produced by a normal NF1 gene, suppresses ras, thus opening up the heart valve. Promising new research has also connected NF1 to cells lining the blood vessels of the heart, with implications for other vascular disorders including hypertension, which affects approximately 50 million Americans. Researchers believe that further understanding of how an NF1 deficiency leads to heart disease may help to unravel molecular pathways involved in genetic and environmental causes of heart disease.
Learning disabilities – Learning disabilities are the most common neurological complication in children with NF1. Research aimed at rescuing learning deficits in children with NF could open the door to treatments affecting 35 million Americans and 5 percent of the world’s population who also suffer from learning disabilities. In NF1 the neurocognitive disabilities range includes behavior, memory and planning. Recent research has shown there are clear molecular links between autism spectrum disorder and NF1; as well as with many other cognitive disabilities. Tremendous research advances have recently led to the first clinical trials of drugs in children with NF1 learning disabilities. These trials are showing promise. In addition because of the connection with other types of cognitive disorders such as autism, researchers and clinicians are actively collaborating on research and clinical studies, pooling knowledge and resources. It is anticipated that what we learn from these studies could have an enormous impact on the significant American population living with learning difficulties and could potentially save federal, state, and local governments, as well as school districts, billions of dollars annually in special education costs resulting from a treatment for learning disabilities.
Memory loss – Researchers have also determined that NF is closely linked to memory loss and are now investigating conducting clinical trials with drugs that may not only cure NF’s cognitive disorders but also result in treating memory loss as well with enormous implications for patients who suffer from Alzheimer’s disease and other dementias.
Deafness – NF2 accounts for approximately 5 percent of genetic forms of deafness. It is also related to other types of tumors, including schwannomas and meningiomas, as well as being a major cause of balance problems.
The enormous promise of NF research, and its potential to benefit over 175 million Americans who suffer from diseases and conditions linked to NF, has gained increased recognition from Congress and the NIH. This is evidenced by the fact that eleven institutes are currently supporting NF research, and NIH’s total NF research portfolio has increased from $3 million in FY1990 to an estimated $24 million in FY2012. Given the potential offered by NF research for progress against a range of diseases, we are hopeful that the NIH will continue to build on the successes of this program by funding this promising research and thereby continuing the enormous return on the taxpayers’ investment.
We respectfully request that you include the following report language on NF research at the National Institutes of Health within your Fiscal Year 2013 Labor, Health and Human Services, Education Appropriations bill.
Neurofibromatosis [NF] – The Committee supports efforts to increase funding and resources for NF research and treatment at multiple NIH Institutes. NF affected children and adults are at significant risk for the development of many forms of cancer; the Committee encourages NCI to increase its NF research portfolio in fundamental basic science, translational research and clinical trials focused on NF. The Committee also encourages the NCI to support NF centers, NF clinical trials consortia, NF preclinical mouse models consortia, and biospecimen repositories. The Committee urges NHLBI to expand its investment in NF based on the increased prevalence of hypertension and congenital heart disease in this patient population. Because NF causes brain and nerve tumors and is associated with cognitive and behavioral problems, the Committee urges NINDS to continue to aggressively fund fundamental basic science research on NF relevant to nerve damage and repair, learning disabilities and attention deficit disorders. In addition, the Committee encourages the NICHD and NIMH to expand funding of basic and clinical NF research in the area of learning and behavioral disabilities. Children with NF1 are prone to the development of severe bone deformities, including scoliosis; the Committee therefore encourages NIAMS to expand its NF1 research portfolio. Since NF2 accounts for approximately 5 percent of genetic forms of deafness, the Committee encourages NIDCD to expand its investment in NF2 basic and clinical research. Based on the increased incidence of optic gliomas, vision loss, cataracts, and retinal abnormalities in NF, the Committee urges the NEI to expand its NF research portfolio. Finally, the Committee encourages NHGRI to increase its investment in NF, given that NF represents a tractable model system to study the genomics of cancer predisposition, learning and behavior problems, and bone abnormalities translatable to individualized medicine.
We appreciate the Subcommittee’s strong support for NF research and will continue to work with you to ensure that opportunities for major advances in NF research are aggressively pursued. Thank you.
_______________________________________________
Below you will find House testimony submitted for the record on behalf of the Neurofibromatosis Network for FY2013.
The Neurofibromatosis Network
House Appropriations Subcommittee on Labor, Health and Human Services, Education
Thank you for the opportunity to submit testimony to the Subcommittee on the importance of continued funding at the National Institutes of Health (NIH) for research on Neurofibromatosis (NF), a genetic disorder closely linked too many common diseases widespread among the American population.
On behalf of the Neurofibromatosis (NF) Network, a national coalition of NF advocacy groups, I speak on behalf of the 100,000 Americans who suffer from NF as well as approximately 175 million Americans who suffer from diseases and conditions linked to NF such as cancer, brain tumors, heart disease, memory loss, and learning disabilities. Thanks in large measure to this Subcommittee’s strong support, scientists have made enormous progress since the discovery of the NF1 gene in 1990 resulting in clinical trials now being undertaken at NIH with broad implications for the general population.
NF is a genetic disorder involving the uncontrolled growth of tumors along the nervous system which can result in terrible disfigurement, deformity, deafness, blindness, brain tumors, cancer, and even death. In addition, approximately one-half of children with NF suffer from learning disabilities. NF is the most common neurological disorder caused by a single gene and three times more common than Muscular Dystrophy and Cystic Fibrosis combined. There are three types of NF: NF1, which is more common, NF2, which primarily involves tumors causing deafness and balance problems, and schwannomatosis, the hallmark of which is severe pain.
While not all NF patients suffer from the most severe symptoms, all NF patients and their families live with the uncertainty of not knowing whether they will be seriously affected because NF is a highly variable and progressive disease.
Researchers have determined that NF is closely linked to cancer, heart disease, learning disabilities, memory loss, brain tumors, and other disorders including deafness, blindness and orthopedic disorders, primarily because NF regulates important pathways common to these disorders such as the RAS, cAMP and PAK pathways. Research on NF therefore stands to benefit millions of Americans:
Cancer – NF is closely linked to many of the most common forms of human cancer, affecting approximately 65 million Americans. In fact, NF shares these pathways with 70% of human cancers. Research has demonstrated that NF’s tumor suppressor protein, neurofibromin, inhibits RAS, one of the major malignancy causing growth proteins involved in 30 percent of all cancer. Accordingly, advances in NF research may well lead to treatments and cures not only for NF patients, but for all those who suffer from cancer and tumor-related disorders. Similar studies have also linked epidermal growth factor receptor (EGF-R) to malignant peripheral nerve sheath tumors (MPNSTs), a form of cancer which disproportionately strikes NF patients.
Heart disease – Researchers have demonstrated that mice completely lacking in NF1 have congenital heart disease that involves the endocardial cushions which form in the valves of the heart. This is because the same ras involved in cancer also causes heart valves to close. Neurofibromin, the protein produced by a normal NF1 gene, suppresses ras, thus opening up the heart valve. Promising new research has also connected NF1 to cells lining the blood vessels of the heart, with implications for other vascular disorders including hypertension, which affects approximately 50 million Americans. Researchers believe that further understanding of how an NF1 deficiency leads to heart disease may help to unravel molecular pathways involved in genetic and environmental causes of heart disease.
Learning disabilities – Learning disabilities are the most common neurological complication in children with NF1. Research aimed at rescuing learning deficits in children with NF could open the door to treatments affecting 35 million Americans and 5 percent of the world’s population who also suffer from learning disabilities. In NF1 the neurocognitive disabilities range includes behavior, memory and planning. Recent research has shown there are clear molecular links between autism spectrum disorder and NF1; as well as with many other cognitive disabilities. Tremendous research advances have recently led to the first clinical trials of drugs in children with NF1 learning disabilities. These trials are showing promise. In addition because of the connection with other types of cognitive disorders such as autism, researchers and clinicians are actively collaborating on research and clinical studies, pooling knowledge and resources. It is anticipated that what we learn from these studies could have an enormous impact on the significant American population living with learning difficulties and could potentially save federal, state, and local governments, as well as school districts, billions of dollars annually in special education costs resulting from a treatment for learning disabilities.
Memory loss – Researchers have also determined that NF is closely linked to memory loss and are now investigating conducting clinical trials with drugs that may not only cure NF’s cognitive disorders but also result in treating memory loss as well with enormous implications for patients who suffer from Alzheimer’s disease and other dementias.
Deafness – NF2 accounts for approximately 5 percent of genetic forms of deafness. It is also related to other types of tumors, including schwannomas and meningiomas, as well as being a major cause of balance problems.
The enormous promise of NF research, and its potential to benefit over 175 million Americans who suffer from diseases and conditions linked to NF, has gained increased recognition from Congress and the NIH. This is evidenced by the fact that eleven institutes are currently supporting NF research, and NIH’s total NF research portfolio has increased from $3 million in FY1990 to an estimated $24 million in FY2012. Given the potential offered by NF research for progress against a range of diseases, we are hopeful that the NIH will continue to build on the successes of this program by funding this promising research and thereby continuing the enormous return on the taxpayers’ investment.
We respectfully request that you include the following report language on NF research at the National Institutes of Health within your Fiscal Year 2013 Labor, Health and Human Services, Education Appropriations bill.
Neurofibromatosis [NF] – The Committee supports efforts to increase funding and resources for NF research and treatment at multiple NIH Institutes. NF affected children and adults are at significant risk for the development of many forms of cancer; the Committee encourages NCI to increase its NF research portfolio in fundamental basic science, translational research and clinical trials focused on NF. The Committee also encourages the NCI to support NF centers, NF clinical trials consortia, NF preclinical mouse models consortia, and biospecimen repositories. The Committee urges NHLBI to expand its investment in NF based on the increased prevalence of hypertension and congenital heart disease in this patient population. Because NF causes brain and nerve tumors and is associated with cognitive and behavioral problems, the Committee urges NINDS to continue to aggressively fund fundamental basic science research on NF relevant to nerve damage and repair, learning disabilities and attention deficit disorders. In addition, the Committee encourages the NICHD and NIMH to expand funding of basic and clinical NF research in the area of learning and behavioral disabilities. Children with NF1 are prone to the development of severe bone deformities, including scoliosis; the Committee therefore encourages NIAMS to expand its NF1 research portfolio. Since NF2 accounts for approximately 5 percent of genetic forms of deafness, the Committee encourages NIDCD to expand its investment in NF2 basic and clinical research. Based on the increased incidence of optic gliomas, vision loss, cataracts, and retinal abnormalities in NF, the Committee urges the NEI to expand its NF research portfolio. Finally, the Committee encourages NHGRI to increase its investment in NF, given that NF represents a tractable model system to study the genomics of cancer predisposition, learning and behavior problems, and bone abnormalities translatable to individualized medicine.
We appreciate the Subcommittee’s strong support for NF research and will continue to work with you to ensure that opportunities for major advances in NF research are aggressively pursued. Thank you.
_______________________________________________
Below you will find public witness testimony that was submitted to the House Appropriations Subcommittee on Defense in support of $16 million for the NFRP in Fiscal Year 2012.
House Appropriations Subcommittee on Defense
Karen Gunsul, Vice President, Washington State Neurofibromatosis Families (WSNF)
April 20, 2011
Thank you for the opportunity to submit testimony to the Subcommittee on the importance of continued funding for research on Neurofibromatosis (NF), a terrible genetic disorder closely linked too many common diseases widespread among the American population.
On behalf of Washington State Neurofibromatosis Families (WSNF) a participant in a national coalition of NF advocacy groups, I speak on behalf of the 100,000 Americans who suffer from NF as well as approximately 175 million Americans who suffer from diseases and conditions linked to NF such as cancer, brain tumors, heart disease, memory loss and learning disabilities. I also speak from the heart as the mother of a son who deals with NF every day. To find treatments and, ultimately, a cure, for this disorder would benefit him and countless others.
In Fiscal Year 2012, I am requesting $16 million to continue the Army’s highly successful Neurofibromatosis Research Program (NFRP), the same amount that was included for the NFRP in Fiscal Year 2011. The Peer-Reviewed Neurofibromatosis Research Program, one of the Department of Defense’s Congressionally Directed Medical Research Programs (CDMRP), is now conducting clinical trials at nation-wide clinical trials centers created by NFRP funding. These clinical trials involve drugs that have already succeeded in eliminating tumors in humans and rescuing learning deficits in mice. Administrators of the Army program have stated that the number of high-quality scientific applications justify a much larger program.
What is Neurofibromatosis (NF)?
NF is a genetic disorder involving the uncontrolled growth of tumors along the nervous system which can result in terrible disfigurement, deformity, deafness, blindness, brain tumors, cancer, and even death. NF can also cause other abnormalities such as unsightly benign tumors across the entire body and bone deformities. In addition, approximately one-half of children with NF suffer from learning disabilities. While not all NF patients suffer from the most severe symptoms, all NF patients and their families live with the uncertainty of not knowing whether they will be seriously affected because NF is a highly variable and progressive disease.
NF is not rare. It is the most common neurological disorder caused by a single gene and three times more common than Muscular Dystrophy and Cystic Fibrosis combined, but is not widely known because it has been poorly diagnosed for many years. Approximately 100,000 Americans have NF, and it appears in approximately one in every 2,500 births. It strikes worldwide, without regard to gender, race or ethnicity. Approximately 50 percent of new NF cases result from a spontaneous mutation in an individual’s genes and 50 percent are inherited. There are three types of NF: NF1, which is more common, NF2, which primarily involves tumors causing deafness and balance problems, and schwannomatosis, the hallmark of which is severe pain. In addition, advances in NF research stand to benefit over 175 million Americans in this generation alone because NF is directly linked to many of the most common diseases affecting the general population.
NF’s Connection to the Military
Neurofibromatosis Research addresses areas of great clinical need directly affecting the health of the war fighter. NF is a complicated condition closely connected to many common diseases and disorders that can lead to unmanageable pain, learning disabilities, cancer, orthopedic abnormalities, deafness, blindness, memory loss, and amputation. NF also involves inflammation similar to that involved in wound healing.
Pain Management - Severe and unmanageable pain is seen in all forms of NF, particularly in one form of NF called schwannomatosis. Over the past 3 years, schwannomatosis research has made significant advances and new research suggests that the molecular or root cause of schwannomatosis pain may be the same as phantom limb pain. Research is currently moving forward to identify drugs that might be able to treat this pain, and these exciting findings could have broad applications for the military.
Wound Healing, Inflammation and Blood Vessel Growth - Wound healing requires new blood vessel growth and tissue inflammation. Mast cells are critical mediators of inflammation in wound healing, and they must be quelled and regulated in order to facilitate this healing. Mast cells are also important players in NF1 tumor growth. In the past few years, researchers have gained deep knowledge on how mast cells promote tumor growth, and this research has led to ongoing clinical trials to block this signaling. The result is that tumors grow slower. As researchers learn more about blocking mast cell signals in NF, this research could be translated to the management of mast cells in wounds and wound healing.
Orthopedic Abnormalities and Amputation - One third of children with NF1 are at risk of developing orthopedic abnormalities that as a result break easily. In the leg particularly, repeated injuries lead to amputation below the knee, often in very young children. Recent research has identified the molecular basis of this, and drug trials in humans will begin in the next year. This research will lead to a deeper understanding of how to heal challenging bone breaks and directly benefit war fighters with major bone breakages or recurring bone breaks that heal poorly.
Three-Dimensional Clinical Imaging Technologies - Because NF tumors are often large and abnormally shaped, they lend themselves well to the emerging technology of volumetric MRI. This is used to monitor tumor volume and growth as well as to monitor the effectiveness of a drug treatment to induce tumor shrinkage or cessation of tumor growth. It is anticipated that MRI volumetric imaging could have broad applications in military use.
Link to Other Illnesses
Researchers have determined that NF is closely linked to cancer, heart disease, learning disabilities, memory loss, brain tumors, and other disorders including deafness, blindness and orthopedic disorders, primarily because NF regulates important pathways common to these disorders such as the RAS, cAMP and PAK pathways. Research on NF therefore stands to benefit millions of Americans:
Cancer – NF is closely linked to many of the most common forms of human cancer, affecting approximately 65 million Americans. In fact, NF shares these pathways with 70% of human cancers. Research has demonstrated that NF’s tumor suppressor protein, neurofibromin, inhibits RAS, one of the major malignancy causing growth proteins involved in 30 percent of all cancer. Accordingly, advances in NF research may well lead to treatments and cures not only for NF patients, but for all those who suffer from cancer and tumor-related disorders. Similar studies have also linked epidermal growth factor receptor (EGF-R) to malignant peripheral nerve sheath tumors (MPNSTs), a form of cancer which disproportionately strikes NF patients.
Heart disease – Researchers have demonstrated that mice completely lacking in NF1 have congenital heart disease that involves the endocardial cushions which form in the valves of the heart. This is because the same ras involved in cancer also causes heart valves to close. Neurofibromin, the protein produced by a normal NF1 gene, suppresses ras, thus opening up the heart valve. Promising new research has also connected NF1 to cells lining the blood vessels of the heart, with implications for other vascular disorders including hypertension, which affects approximately 50 million Americans. Researchers believe that further understanding of how an NF1 deficiency leads to heart disease may help to unravel molecular pathways involved in genetic and environmental causes of heart disease.
Learning disabilities – Learning disabilities are the most common neurological complication in children with NF1. Research aimed at rescuing learning deficits in children with NF could open the door to treatments affecting 35 million Americans and 5 percent of the world’s population who also suffer from learning disabilities. In NF1 the neurocognitive disabilities range includes behavior, memory and planning. Recent research has shown there are clear molecular links between autism spectrum disorder and NF1; as well as with many other cognitive disabilities. Tremendous research advances have recently led to the first clinical trials of drugs in children with NF1 learning disabilities. These trials are showing promise. In addition because of the connection with other types of cognitive disorders such as autism, researchers and clinicians are actively collaborating on research and clinical studies, pooling knowledge and resources. It is anticipated that what we learn from these studies could have an enormous impact on the significant American population living with learning difficulties and could potentially save federal, state, and local governments, as well as school districts, billions of dollars annually in special education costs resulting from a treatment for learning disabilities.
Memory loss – Researchers have also determined that NF is closely linked to memory loss and are now investigating conducting clinical trials with drugs that may not only cure NF’s cognitive disorders but also result in treating memory loss as well with enormous implications for patients who suffer from Alzheimer’s disease and other dementias. Indeed, one leading Army funded researcher is pursuing parallel research into both NF and Alzheimer’s simultaneously.
Deafness – NF2 accounts for approximately 5 percent of genetic forms of deafness. It is also related to other types of tumors, including schwannomas and meningiomas, as well as being a major cause of balance problems.
The Army’s Contribution to NF Research
While other federal agencies support medical research, the Department of Defense (DOD) fills a special role by providing peer-reviewed funding for innovative, high-risk/high-reward medical research through the CDMRP. CDMRP research grants are awarded to researchers in every state in the country through a competitive two-tier review process. These well-executed and efficient programs, including the NFRP, demonstrate the government’s responsible stewardship of taxpayer dollars.
Recognizing NF’s importance to both the military and to the general population, Congress has given the Army’s NF Research Program strong bipartisan support. From FY96 through FY11 funding for the NFRP has amounted to $230.05 million, in addition to the original $8 million appropriation in FY92. In addition, between FY96 and FY09, 245 awards have been granted to researchers across the country.
The Army program funds innovative, groundbreaking research which would not otherwise have been pursued, and has produced major advances in NF research, including conducting clinical trials in a nation-wide clinical trials infrastructure created by NFRP funding, development of advanced animal models, and preclinical therapeutic experimentation. Because of the enormous advances that have been made as a result of the Army’s NF Research Program, research in NF has truly become one of the great success stories in the current revolution in molecular genetics. In addition, the program has brought new researchers into the field of NF. However, despite this progress, Army officials administering the program have indicated that they could easily fund more applications if funding were available because of the high quality of the research applications received.
In order to ensure maximum efficiency, the Army collaborates closely with other federal agencies that are involved in NF research, such as the National Institutes of Health (NIH). Senior program staff from the National Institute of Neurological Disorders and Stroke (NINDS), for example, sits on the Army’s NF Research Program Integration Panel which sets the long-term vision and funding strategies for the program. This assures the highest scientific standard for research funding, efficiency and coordination while avoiding duplication or overlapping of research efforts.
Thanks in large measure to this Subcommittee’s support; scientists have made enormous progress since the discovery of the NF1 gene. Major advances in just the past few years have ushered in an exciting era of clinical and translational research in NF with broad implications for the general population. These recent advances have included:
• Phase II and Phase III clinical trials involving new drug therapies for both cancer and cognitive disorders;
• Creation of a National Clinical and Pre-Clinical Trials Infrastructure and NF Centers;
• Successfully eliminating tumors in NF1 and NF2 mice with the same drug;
• Developing advanced mouse models showing human symptoms;
• Rescuing learning deficits and eliminating tumors in mice with the same drug;
• Determining the biochemical, molecular function of the NF genes and gene products;
• Connecting NF to more and more diseases because of NF’s impact on many body functions.
Fiscal Year 2012 Request
The Army’s highly successful NF Research Program has shown tangible results and direct military application with broad implications for the general population. The program has now advanced to the translational and clinical research stages, which are the most promising, yet the most expensive direction that NF research has taken. The program has succeeded in its mission to bring new researchers and new approaches to research into the field. Therefore, continued funding is needed to take advantage of promising avenues of investigation, to continue to build on the successes of this program, and to fund this promising research thereby continuing the enormous return on the taxpayers’ investment.
I respectfully request an appropriation of $16 million in the Fiscal Year 2012 Department of Defense Appropriations bill for the Army’s Neurofibromatosis Research Program.
In addition to providing a clear military benefit, the DOD’s Neurofibromatosis Research Program also provides hope for the 100,000 Americans who suffer from NF, as well as over 175 million Americans who suffer from NF’s related diseases and disorders. Leading researchers now believe that we are on the threshold of a treatment and a cure for this terrible disease. With this Subcommittee’s continued support, we will prevail. Thank you for your support.
