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Neurofibromatosis (NF) is a set of genetic disorders that can cause tumors to develop and grow along various types of nerves. The tumors may also affect the development of non-nervous system tissues such as skin and bone.

There are three types of NF tumors that result from mutation or loss of different tumor suppressor genes:

• Neurofibromatosis type 1 (NF1) is the most frequent inherited cause of brain and nerve tumors. One in every 3,000 children is born with NF1, making it also one of the most common inherited human diseases worldwide. Enlargement and deformation of bones may also occur. Approximately 50% of people with NF1 also have learning disabilities. NF1 is caused by a mutation or loss of the tumor suppressor gene NF1.

• Neurofibromatosis type 2 (NF2) is much rarer, occurring in one in 25,000 births. NF2 is characterized by the development of multiple tumors on the cranial and spinal nerves. The hallmark of NF2 is the formation of tumors that affect auditory nerves. Hearing loss beginning in the teens or early twenties is typically the first symptom of NF2. NF2 is caused by a mutation or loss of the tumor suppressor gene NF2.

• Schwannomatosis is even rarer than NF2, affecting one in 40,000 individuals. SImilar to NF1 and NF2, Schwannomatosis tumors can develop on cranial, spinal and/or peripheral nerves. Although patients with Schwannomatosis do not have learning disabilities, they experience chronic pain and occasionally numbness, tingling and weakness. The candidate Schwannomatosis tumor suppressor gene is named INI1.

The National Institutes of Health (NIH) is the primary source of federal funding for biomedical research. However, other agencies also support research initiatives. In 1996, Congress added Neurofibromatosis to the Congressionally Directed Medical Research Program (CDMRP-NFRP). This program has been responsible for many advances in NF research, including NF mouse models, learning disabilities and nerve signaling pathways. In 2005, the Neurofibromatosis Research Program (NFRP) established the NF Clinical Trials Consortium, which is comprised of 10 major hospitals nationwide. The Consortium was established, not for drug discovery, but as a pipeline to test drugs repurposed to treat NF, including rapamycin (a relatively new immunosuppressant drug) and lovastatin (a statin used for lowering cholesterol). The Consortium will initially focus on NF1 for proof of concept. Once established, it will have the option of expanding to encompass NF2 and Schwannomatosis studies.

NF research program funding in jeopardy

The U.S. House and Senate included an $8 million appropriation for the CDMRP-NFRP in the FY2008 Defense Bill. This is a decrease of $2 million from 2007 and is over a 66% decrease from the high-water mark of $25 million in FY2005. Recently, I wrote about Flat Funding of Biomedical Research and The Threat to America’s Health. Separate from the NIH, the CDMRP is another funding source that supports research initiatives. The drastic funding cuts in the CDMRP-NFRP, specific to NF studies, endanger the research investment made to date, particularly with the NF Clinical Trials Consortium described above.

The Children’s Tumor Foundation (CTF), a non-profit medical foundation dedicated to improving the health and well being of individuals and families affected by the neurofibromatoses, is the largest non-government funder of NF research in the world. In 1991, the CTF began a formal advocacy and lobbying program for federal funding of NF research. Recently, the CTF announced an advocacy campaign to increase federal funding of the CDMRP-NFRP [1]:

We are all aware of the budget pressures our country faces, and understand that the $25 million funded in 2005 is not realistic in the current environement. However, this small program has accomplished so much, and as we enter what we believe will be a period of rapidly increasing clinical trials, this is a particularly important time for continued support of this funding. We are asking all of you to contact your Congressman and Senators to seek their support. There is much discussion of earmark reform in Washington. It is important to note that this funding is not an earmark. It is not directed to any one institution, state or district. It is a long standing program that makes grants solely on a peer review basis. Further, this is not a partisan issue - this funding has benefited over the years from strong support from both Democrats and Republicans. The accomplishments and return on investment from the CDMRP are a shining example of what the federal government can achieve when legislators work with the scientific community and non-profit organizations.

Indeed, the CDMRP-NFRP is a small program. Congressional appropriations for NF from 1996 to 2008 totaled just $190.3 million. By comparison, CDMRP funding for breast cancer totaled $2222.7 million, for prostate cancer, $890 million [2]. Nevertheless, CDMRP funding for NF research in 2008 is critically important to address the needs of translational research (meaning to connect basic research to patient care), complications of NF with high morbidity and mortality, and refinement and standardization of imaging techniques and biomarkers for use in future clinical trials.

You can read more on the Children’s Tumor Foundation and Neurofibromatosis here at Highlight HEALTH. Additional non-profit organization resources are listed in the Highlight HEALTH Web Directory.

I’m actively involved in neuro-oncology, specifically NF research, and can attest to the importance of CDMRP-NFRP funding. I encourage you to take a moment and email your Senator and Representative and urge them to support increased Neurofibromatosis research funding through the CDMRP. You can find your legislators contact information by visiting the House and Senate websites. For the House website, simply enter your zip code in the box in the upper left corner; for the Senate website, select your state from the pulldown menu in the upper right corner. Use the contact information provided to email, fax or mail your request for support.

UPDATE: April 1st, 2008

Sample letters are now available (in MS Word format) for download, making it that much easier to email, fax or mail your Senator and Representative.

References

1. The Children’s Tumor Foundation: Advocacy. Accessed 2008 Mar 30.
2. Congressionally Directed Medical Research Programs: Funding History. Accessed 2008 Mar 30.

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According to a report released earlier this week, five years of consecutive flat or below-inflation funding of the budget of the National Institutes of Health (NIH) is discourage promising young researchers and endangering the future of America’s health [1]. The study warns that many of the brightest young minds are leaking out of the academic research pipeline because they no longer see a promising career in academic science. Indeed, America could lose a generation of promising researchers to other careers and other countries.

The report, “A Broken Pipeline? Flat Funding of the NIH Puts a Generation of Science at Risk,” was written by a consortium of seven institutions, including:


• Brown University
• Duke University
• Harvard University
• The Ohio State University
• Partners Healthcare
• University of California Los Angeles
• Vanderbilt University

The report profiles 12 exceptional junior researchers from institutions across the country who were selected by senior scientists and university leadership for their potential to make significant scientific contributions. The young researchers are working on new methods to manipulate adult stem cells to repair the heart, identifying critical biological pathways involved in cancer and progressive brain diseases, determining the mechanisms of pain and heat sensation, searching for genetic causes of age-related hearing loss, and using new technologies to detect kidney disease in its earliest stages.

The report, which I’ve linked to below, summarizes the problem quite succinctly:

Science itself is taking a hit. As the NIH has less grant money to award, the scientists who review grant applications are predictably becoming more and more risk averse in their evaluations, preferring to see incremental steps rather than bold visions. This conservatism among reviewers is changing the way researchers write grant applications and design experiments. There has been a fundamental narrowing of the scientific vision, with the primary scientific query shifting from “what is possible?” to “what is fundable?” 


The harmful effects of these breaks in the scientific pipeline are felt, ultimately, in America’s health and economy. Conservatism and delays at the research bench reduce the scope and pace of scientific discovery and, eventually, the rate at which medical advances improve health outcomes for all of us.

The report can be downloaded directly from BrokenPipeline.org. You can also download a related report released last year by a group of nine institutions across the country titled “Within Our Grasp — Or Slipping Away? Assuring a New Era of Scientific and Medical Progress”. The report showed how flat NIH funding, combined with inflation, was eroding research budgets and forcing scientists to downsize their laboratories and abandon innovative and promising work [2].

In spite of all this, the President’s budget proposal for fiscal year 2009 recommends a sixth year of flat (and with inflation, decreased) funding for the NIH.

What can you do?

Congress has begun work on funding for biomedical research to improve health in fiscal year 2009. Several Representatives are leading an effort to increase NIH finding by 6.5% and have invited their colleagues to join them on a letter to Appropriations Chair David Obey (WI) and Ranking Member Jerry Lewis (CA). Research!America, an alliance for discoveries in health, makes it easy to contact your Representative and urge them to sign this important letter.

Biomedical research innovation and advancement are critical to transformation of medicine from reactive to preventative, predictive, and personalized. I encourage you to support increased funding for research to improve American’s health.

UPDATE: March 14th, 2008

Research!America reports that the Senate overwhelmingly approved an amendment to the FY09 budget resolution that calls for an extra $2.1 billion to the NIH budget. You can read more about this First Step Toward Unflattening the NIH Budget at Research!America.

References

1. 
A Broken Pipeline? Flat Funding of the NIH Puts a Generation of Science at Risk. Brown University, Duke University, Harvard University, The Ohio State University, Partners Healthcare, the University of California Los Angeles, and Vanderbilt University. 2008 Mar 11.
2. Within Our Grasp — Or Slipping Away? Assuring a New Era of Scientific and Medical Progress. The University of California, Columbia University, Harvard University, Johns Hopkins University, Partners Healthcare, The University of Texas, Washington University in St. Louis, The University of Wisconsin, and Yale University. 2007 Mar 19.

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Jonathan Eisen, an evolutionary biologist at U.C. Davis Genome Center, has been named the first Academic Editor-in-Chief at the Public Library of Science (PLoS) journal PLoS Biology. He wrote an editorial published Tuesday on the PLoS Biology website that discusses his conversion and commitment to open-access publishing. His personal experience exemplifies what to me is the principle reason for open access [1]:

So there I was — a scientist and a taxpayer — desperate to read the results of work that I helped pay for and work that might give me more knowledge than possessed by our doctors. And yet either I could not get the papers or I had to pay to read them without knowing if they would be helpful.

Decisions in health and medicine frequently aren’t black and white. In the Internet age, more and more people are using the web to guide healthcare decision making. Allowing healthcare consumers and e-patients access to evidence from biomedical research studies will enable them to make more informed decisions about their healthcare. Open access is pivotal to that empowerment.

Why is Open Access Important?

The foundation for future progress in health and medicine is biomedical research. Open access is advantageous for the way scholarly research is executed and how results and conclusions are used.

Open access publishing provides exposure to the widest audience. Anyone interested in the research can read it, which translates into increased usage and greater impact. Open Access also means greater visibility, accessibility and impact of scientific research. A recent study of open access to research literature provided evidence that open-access articles are more immediately recognized and cited than non-open-access articles [2], suggesting that open access is likely to benefit science by accelerating dissemination of research findings. And clearly, faster diffusion of research impacts future investigation. Indeed, everyone has an interest in “the efficient and effective progress of scholarly endeavor” [3].

The NIH Public Access Policy

On April 7, 2008, the National Institutes of Health (NIH) public access policy goes into effect. The policy makes mandatory a previously voluntary NIH initiative to submit electronic versions of final, peer-reviewed manuscripts upon acceptance for publication to the National Library of Medicine’s PubMed Central. Submitted articles will be made publicly available no later than 12 months after the official date of publication. The policy applies to any journal article supported in whole or part by funding from the NIH.

However, some object to the policy, including The Association of American Publishers, who is questioning the policy’s legality, claiming that it undermines publisher copyright and is inconsistent with U.S. intellectual property laws. The AAP wants the NIH to get public input in a formal rulemaking [4].

What can you as a healthcare consumer do? Tell your Senators and Representatives that you expect your government to support science and the public interest over the private interests of publishers. Insist that taxpayer-funded research be made available free of charge to the public.

More information for faculty, administrators, librarians, students, foundations, societies and governments on how to support open access can be found in Peter Suber’s article What you can do to promote open access.

References

1. Eisen JA. PLoS Biology 2.0. PLoS Biol. 2008 6(2): e48 doi:10.1371/journal.pbio.0060048.
2. Eysenbach G. Citation advantage of open access articles. PLoS Biol. 2006 May;4(5):e157. Epub 2006 May 16.
   View abstract
3. Swan A. Open Acess: Why should we have it? Cahiers de la Documentation: Bladen voor Documentatie. 2006.
4. Sciencescope. Science. 2008 Jan 11;319(5860):145.

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