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The Children's Tumor Foundation and the Texas Neurofibromatosis Foundation (Texas NF) have announced a strategic partnership to fund critical NF research.   The partnership speaks to the growing spirit of collaboration among the two organizations and Texas NF’s commitment to funding the best NF research wherever it may be, on behalf of its constituents.

The partnership will fund a two year research project conducted by Dr. Jody Fromm, Ph.D., at Harvard Medical School/Brigham and Women’s Hospital on malignant peripheral nerve sheath tumors (MPNSTs) in individuals affected by NF.  MPNSTs are a form of cancer that occurs on connective tissue throughout the body.  MPNSTs affect 5-15% of individuals affected by NF at some point in their lives.  The tumors are often inoperable, and progress rapidly. 

Read more here about this exciting collaboration!

The Children’s Tumor Foundation is conducting a survey to find out the extent to which the drug bevacizumab (better known by its trade name Avastin) has been/is currently being prescribed to individuals with NF2, both inside and outside the context of organized clinical trials.  This information will be extremely helpful in understanding current use patterns of Avastin in the NF2 population.    Collectively this data could be helpful in planning future clinical trials. This survey may be taken anonymously, please provide as much information and use as much space as you wish. You need not complete all questions if you are not sure how to respond to some. You need not provide your name or your doctor/clinic name if you do not wish to. The data collected through this survey will be collated, tabulated and graphed (e.g. to show number of respondents, responses to certain questions, etc.) without identifying information on survey respondents. This data will be emailed to all survey respondents that provide an email address. The collective data may be shared with researchers/physicians and more publicly without any information that identifies survey respondents.  

To download this survey as a Word document please click here.  To download the survey as a pdf please click here.

Please email or FAX your completed survey responses to me - Dr. Kim Hunter-Schaedle - at khs@ctf.org This e-mail address is being protected from spambots. You need JavaScript enabled to view it or 212-747-0004.

In promising news, the United States Food and Drug Administration is holding two days of panel hearings this week to address the challenge of how to get biotech and pharma companies more engaged in developing drug treatments for orphan conditions - defined as any condition affecting fewer than 200,000 Americans.   With estimated US statistics of around 100,000 individuals affected by NF1, 12,000 by NF2 and 7,500 by schwannomatosis, the forms of neurofibromatosis fit well within this cap. 

All told, one in ten Americans is affected by one of more than 6,000 orphan diseases, so this is a population that cannot be overlooked forever.  There has been a great deal of talk from a number of companies such as Pfizer and Novartis in the last few months expressing an interest in rare diseases - but this has yet to translate into real action.  Neurofibromatosis has the added challenge that the condition can affect individuals in many different ways - ranging from a variety of nerve tumors, to bone dysplasia, to learning disabilities - limiting patient numbers in any demographic even more.  It is hard to engage companies in neurofibromatosis and other orphan conditions because the profit margins are likely to be very small at best. The Children's Tumor Foundation works to  break down these barriers through programs like our NF Preclinical Consortium and Drug Discovery Initiative, which have attracted and engaged companies like Novartis, Genentech and Avila Therapeutics with positive preliminary results. That said, the real challenge will come when a potentially effective drug is identified and needs expanded to as large scale clinical trial - something for which we'll need the backing and heft of industry.  Only the FDA can hold industry's feet to the fire on this matter. So we'll watch the outcome of these panels closely.

In other news, the National Institutes of Health has also been pushing for advancement in orphan conditions in recent times. Now  they are promoting 500 licensing opportunities in NIHs possession, which have potential applications for orphan conditions, and which they'd like to license out to interested parties. The Foundation will endeavor to learn if any of these offerings are related to neurofibromatosis and see if we can facilitate their advancement.

The following was written by Dr. Kim Hunter-Schaedle.

There are many reputable medical research foundations but the Children’s Tumor Foundation sets itself apart with our commitment to fiscal responsibility and transparency.  As a recipient of Charity Navigator’s four-star (highest) rating we have demonstrated that a dollar invested in the Foundation is a dollar well spent.  Whether you are interested in helping to treat learning disabilities, deafness, blindness, scoliosis, bone deformities, cancer or any of the other complications of NF, here are five reasons to fund medical research through the Children’s Tumor Foundation:

1. More of your money gets to the researcher: if you make a donation to a university, hospital or other institution, you may feel that this is the best way to make sure your donation gets directly to the researcher of your choice. However, many universities, hospitals and institutions hold back as much as two-thirds of your donation in ‘indirect,’ ‘overhead’ or ‘administrative costs,’ because this is the amount of ‘indirect’ costs that the institution can claim from National Institutes of Health grants – the gold standard. So from a donated grant of $100,000, it is possible the researcher will see only $30,000.
   In contrast, CTF caps universities at 10% maximum overheads on our grants. So from a $100,000 grant, the researcher will see $90,000. To date we have not had an institution decline a grant because of this. 

2. Funding the best research, wherever it is: Many people feel inclined to keep their funding local and/or feel attached to a specific researcher at a specific institution. But how do you know that researcher is at the cutting edge of the field? The answer is in most cases you wont know.
   An investment in the Children’s Tumor Foundation is an investment in the very best science in the world wherever it may be.  All CTF funded programs are open to applicants worldwide. We fund only the top tier applications recommended by our Research Advisory Board which is comprised of international experts on neurofibromatosis, cancer and related research areas.

3. Be part of a pipeline, and put funding where it is most needed today: If you donate funds directly to researcher or institution, how do you know that their work is not currently being duplicated elsewhere in the world and funded by someone else?
   The Foundation conducts ongoing ‘landscape monitoring’ to determine which areas of research are being funded at any one time. This information informs our strategic planning to determine the areas of research most in need of funding in order to accelerate new discoveries to clinical therapies.

4. Oversight and accountability: If you donate funds directly to a researcher or institution, how and by whom is progress monitored? Can you guarantee the feedback you will receive?
   All research funded by the Foundation is monitored through ongoing progress reporting and follow-up even after our funding has expired– for example, our awardees success in securing follow-on funding. This information allows us to monitor the long-term impact of CTF funding, and to integrate that information back into the neurofibromatosis landscape to inform future decision making on funding directions to take.

5. Ensure discoveries move forward: If you donate funds directly to a researcher or institution, and a discovery is made leading to a patent, how can you be sure it will be advanced for the purposes for which you’ve funded rather than a potentially more lucrative purpose?
   Recipients of Children’s Tumor Foundation funding are required to sign a CTF Patent Policy.  This provides the Foundation the opportunity to have a ‘seat at the table’ when decisions are made at the institution about patenting and licensing a discovery; rights for CTF to claim back the discovery or patent if it offers promise for patients but the institution does not advance it; and, if the discovery becomes a commercial success, a share in the revenue stream for the Foundation to plow back into other research projects.

If you have any questions about any of the information provided in this space please fee free to ask below or email us at info@ctf.org. 

After writing yesterday's post on personalized medicine and genomics I was directed (hat tip to Garrett) to a special report on the human genome in the current issue of the Economist titled Biology 2.0.  Below are clips from the first page, but the entire article is well worth reading to understand where we are today in genetic research.

"TEN years ago, on June 26th 2000, a race ended. The result was declared a dead heat and both runners won the prize of shaking the hand of America’s then president, Bill Clinton, at the White House. The runners were J. Craig Venter for the private sector and Francis Collins for the public. The race was to sequence the human genome, all 3 billion genetic letters of it, and thus—as headline writers put it—read the book of life.

...And then it all went terribly quiet. The drugs did not appear. Nor did personalised medicine. Neither did the genetic underclass. And the money certainly did not materialise. Biotech firms proved to be just as good at consuming cash as dotcom start-ups, and with as little return. The casual observer, then, might be forgiven for thinking the whole thing a damp squib, and the $3 billion spent on the project to be so much wasted money. But the casual observer would be wrong. As The Economist observed at the time, the race Dr Venter and Dr Collins had been engaged in was a race not to the finish but to the starting line. "

The current articles on the human genome highlight the importance of the recent court decision on gene patents.   Genetic research is just getting started in leveraging the knowledge of the Human Genome Project.  It is our job as a foundation to ensure that NF research is front and center in exploring these new methods and technologies.

John

Last week there were several interesting articles on personalized medicine that are of interest to the NF community.  

The NY Times published a two part series headlined A Decade Later, Genetic Map Yields Few New Cures by Nicholas Wade, and Awaiting the Gene Payoff by Andrew Pollack.

It is difficult to argue that the expected benefits from  the Human Genome Project  have  met projections  made at the time of the projects completion in 2000.  In hindsight these expectations look overly optimistic.  However, as we look at the research landscape today and all the work that is being done, I can't help but borrow the baseball metaphor that we are only in the second inning.

Evidence of this is an article in Wired magazine about an announcment expected this Thursday of a joint project between 23andMme, the Michael J. Fox Foundation and the Parkinson’s Institute and Clinical Center to enroll up to 10,000 people with Parkinson’s Disease, get them genotyped using the 23andMe platform, and collect  phenotypic information. It is a long stated goal of the Children's Tumor Foundation to establish a patient registry and bio bank that will bring these capabilities to the NF patient and research community.  While we are not in a position to announce anything today, it is an area of key interest.  More to come...

John

Those of you following our blog this month will have had a taste of the sheer enthusiasm that we felt at the 2010 Neurofibromatosis Conference in Baltimore.  Nothing short of 'groundbreaking' describes the progress being made today to understand and find effective treatments  NF1, NF2 and schwannomatosis  - and the Children's Tumor Foundation is front and center in driving this through our research grant programs.  Many of the 300+ researchers and clinicians attending talked about how important the Children's Tumor Foundation had been in funding their research and getting new ideas 'jump started'.

To hear about progress in NF research and CTF's impact on this visit www.ctf.org/videos to watch these short videos from the NF Conference featuring such luminaries as Dr. Bruce Korf, Dr. Sue Huson, Dr. Vic Riccardi and Dr. Jaishri Blakeley. Also included is an exciting announcement from CTF Executive Director Dr. George Orfanakos on a funding partnership between the Children's Tumor Foundation and the Texas Neurofibromatosis Foundation.

Many of us have been heartened by the promising data emerging from the reports of small clinical trials that assess the drug bevacizumab (known more widely by its tradename, Avastin) for treatment of vestibular schwannoma tumors in individuals with NF2.  In addition to these controlled trials, a number of persons in the NF2 community have reported using Avastin individually and in some cases seeing promising results.

The Children's Tumor Foundation is conducting an informal NF2 Survey to accumulate as much information as we can about thebroader use of Avastin by NF2 patients and the impact of this drug on NF2 tumor growth/hearing/etc.  If you have NF2 and have taken Avastin, either in the context of a clinical trial, or individually, we invite you to take our brief survey. To receive a copy of the survey please contact me at khs@ctf.org. 

The data collected from the survey will be collated and shared with those individuals who respond to the survey. In the light of the fact that candidate drug treatments for NF2 are really now just emerging, we are also hopeful that this data will be uniquely informative for the researchers and clinicians whose goal is to find effective drug treatments for NF2.

There have been some positive reports from pilot use of the drug Gleevec (Imatinib Mesylate) in NF1 plexiform neurofibromas. Now a second pilot study of Gleevec for treatment of plexiforms has been announced and is open for recruitment at Indiana University. This is an interventional, open-label study (i.e. no placebo arm - if you participate you will receive drug). The study needs 20 patients aged 18-65. For more information on the trial including eligibility criteria for participation, click here or got to www.clinicaltrials.gov and search 'neurofibromatosis' for a list of all currently trials accepting those with neurofibromatosis.

The final morning of the 2010 NF Conference included some great gems. Two parallel abstract sessions opened the day.  One session focused on NF1 basic science abstracts; presentations included a significant focus on tumor initiation and malignancy and featured STAT3 as a candidate target for MPNST formation (Jianquiang Wu, Cincinnati), and two talks on the sources of cells that initiate tumor foramtion in NF and cause advancement to MPNST (Johanna Buchstaller, Michigan and Faris Farasatti, Kansas).  The other session covered basic and translational NF2 research, notably including well-attended presentations of the Phase II bevacizumab (Avastin) clinical trials from Massachusetts General Hospital (Scott Plotkin) and Phase 0 and Phase II lapatinib clinical trials ongoing at Johns Hopkins University and NYU Langone Medical Center (Matthias Karajannis).  As we reported from Las Vegas, these trials are moving forward and expanding; for Avastin there will be 2 US trials centered at MGH and Johns Hopkins respectively with different entry criteria.  Additional NF2 talks in this sesion included Janet Oblinger (Ohio State University) with an update on NF2 preclinical drug screening studies using OSU-03012 which has shown some promise in animal models (these studies were originally funded by a CTF DDI Award).  
A high-quality session closed out the day with the theme 'across the Ras-MAPK pathway' and touched on some aspects of neurofibromatosis  not already covered in the  Conference. Dr. Jonathan Epstein (U. Pennsylvania) reviewed progress in his research to understand cardiovascular manifestations in NF1, using zebrafish genetic models.  Cardiovascular complications of NF1 are understudied but can be a significant concern; and they have come to the fore in recent years due to our increased understanding of the role of the inflammatory system in NF1. Zebrafish are transparent and allow Dr. Epstein to image vascular flow in living animals.  The fish can also be bred easily with different genetic mutations making them a very useful model to unravel vascular complications. Having generated some fish with significant vascular provblems, Dr. Epstein can use these to test drugs that might correct the vasculature and could be NF1 clinical therapies.  Dr. Dave Stevenson (Utah) gave a fascinating overview of the many bony abnormalities that affect an estimated 38% persons with NF1 and which are also seen in other 'Ras-MAPK' conditions such as Noonan syndrome. Dr. Stevenson is working with a colalborative group planning the first Phase II biologic therapy intervention for NF1 long bone dysplasia to commence later this year.  This is exciting as today, children with long bone dysplasia often face amputation as the best available outcome.  Dr. Eric Legius (Leuven) provided an update on Legius Syndrome. Dr. Legius actually saw the first Legius Syndrome patient in 1980; but it was many years later, in 2001, when the SPRED-1 gene was identified through studies in flies, that he defined the condition at the molecular and genetic level.  Legius Syndrome has the appearance of 'mild' NF1 (cafe-au-lait spots; cognitive issues; mild bony malformations; but nerve tumors and vascular malformations seen only in very rare cases) and is due to mutation of the SPRED-1 gene on Chromosome 15.   142 patients with Legius Syndrome have now been identified worldwide.  This is a very rare condition and includes only around 1-4% of individuals who have had a clinical diagnosis of NF1. As a next step, Dr. Legius proposed the organization of an international clinical an molecular database of Legius Syndrome patients so the conditio can be better understood. 
The 2010 NF Conference ended with its traditional rousing cheer and lots of hope and promise. For me this ws the best NF Conference I have seen to date in terms of the quality of research ongoing and the advances made. Thanks to the 2010 NF Conference Chairs Sue Huson (Manchester) and Filippo Giancotti (Sloan Kettering) for putting on such a great event! Next: we hope for a professional publication of the 2010 NF Conference proceedings  as we did in 2009.