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The CTF poster 'Neurofibromatosis Networking'  has been selected once again for presentation - this time at the New York Biotechnology Association Annual Meeting.  This poster highlights the terrific resources that CTF has developed for working with biotechnology companies and to engage them in neurofibromatosis research - including the NF Preclinical Consortium, which has now established multiple collaborations with industrial partners, and the  national NF Clinic Network which in 2010 saw 10,000 persons with NF.   This poster was also selected for display at the Massachusetts Biotechnology Coucil Annual Meeting a few weeks ago and provided an opportunity for us to identify new commerical collaborators and partners in our goal to find treatments for neurofibromatosis. We aim to network with further partners at NYBA!

The National Institutes of Health (NIH) is offering grant support for a U.S.-China Biomedical Collaborative to support research collaborations between an intramural NIH researcher (i.e. researcher employed at NIH) and a researcher based in China. The program will consider applications in a number of research areas but as always we’d love to see some of this money go to neurofibromatosis research!   NIH intramural researcher Dr. Douglas Stewart is seeking a collaborator in China to develop a research application focused on NF1.  Funds available are $100,000 to the NIH investigator and 300,000 Renminbi (Chinese currency) the China-based researcher. Chinese co-investigators need to be current or former grantees of the National Natural Science Foundation of China (NSFC). Deadline for application is April 14 so act now! More information: contact khs@ctf.org. 

Timmy Mani, a Children’s Tumor Foundation 2008-2010 Young Investigator Award recipient, has published a paper in Molecular Cell Biology describing new findings that help understand how the NF2 protein merlin regulates cell growth. These findings were made during Timmy’s time as a CTF YIA in the lab of Dr. Wallace Ip at the University of Cincinnati.  

It is known that merlin function requires it to bind to the interior of the cell membrane. Timmy’s research shows that a key player in making this binding happen is the phosphoinositide PIP2. When merlin protein is modified so that it can no longer bind PIP2, the cells grow uncontrollably. This finding suggests an important role for PIP2 in controlling cell growth and that PIP2 function will be an interesting area to explore in looking for new drug targets for NF2 therapies.

The panel discussions at this week's annual meeting of the Massachusetts Biotechnology Council that I attended on behalf of the Children's Tumor Foundation included leadership from many drug giants: Millenium, Sanofi-Aventis, Novartis and AstraZeneca to name a few. From all of them the message was the same: the rules of drug development are changing - and in a big way.  We are watching these issues as they will be of growing importance in neurofibromatosis as we see more drugs getting into clinical trials.

First and foremost, we are seeing the emergence of personalized medicine. This is based in understanding an individual's genetic makeup, and then identifying why a person develops cancer or heart disease or any other malady. This information helps doctors to determine which patients are likely to benefit from specific molecularly-targeted medicines. Though this seemed like science fiction just a few years ago, the first results of personalized medicine are already emerging specifically from cancer trials. The result we hope will be faster  and more meaningful clinical trials and a faster path of getting drugs to the market.

In response to this, drug companies are realizing that if they are developing a new drug they need to be thinking about developing a 'companion diagnostic' - e.g. a blood test so they can identify, prior to prescribing the drug, the patients that will most benefit from the treatment. This is revolutionizing the way drug companies are planning their drug development strategies and excitingly encouraging partnering between drug and diagnostic companies early on to ensure that no promising drug is left behind due to lack of a diagnostic.

This partnership extends to considerations about how the Food and Drug Administration will co-approve drug and diagnostic (there is noise about a new office opening at FDA to aid with this). And finally ... will insurance pay for this?  Drug companies are realizing that once they have a promising new drug, conversations with those overseeing reimbursement need to be a priority. 

Endnote: our poster 'Neurofibromatosis Networking' presented Monday night garnered a significant amount of attention from attendees and made some helpful new connections for NF in the drug world. Attendees were give three '$1 million dollar' bills to 'invest' in the posters and though we did not win, our envelope was quite full!

 

Today I will attend the annual Massachusetts Biotech Meeting (Mass Bio) . This year's theme, 'Every Patient Tells  a Story' speaks to the growing role of patients and their advocates, including foundations like the Children's Tumor Foundation that fund early stage research ideas, in providing a bridge between basic research and the pharmaceutical and biotechnology companies so that  - in our case - we help drive progress toward the development of drug treatments for neurofibromatosis. 
Today I will be presenting a poster 'Neurofibromatosis Networking' that showcases to potential industry collaborators all of the resources that CTF has developed to make neurofibromatosis drug development easier, including our NF Preclinical Consortium and 44-site NF Clinic Network which last year cared for 10,000 NF patients.  Look out for updates from the meeting later this week!   

National Insitutes of Health Director Dr. Francis Collins participated yesterday in a public webcast to answer questions on the NIH's proposed National Center for Advancing Translational Science (NCATS) slated to open October 1. NCATS is to take the lead role at NIH for advancing scientific research discoveries to the clinic, and will become an umbrella center for ongoing NIH-funded programs that are already addressing this need.  NCATS has met with some controversy and concern that funding 'drug development' should not be a primary mandate of the NIH and that it could cannibalize funding that is available for basic research. This comes at a time when the NIH budget is already stretched. At the same time, NIH can fill a vital need that is largely not being supported by industry, getting discoveries ready for intial clinical studies. In the Q&A Dr. Collins indicated that a key reason why this initiative is so important is that the science itself has advanced to a point that there are many discoveries that need to be advanced  to ensure development of treatments for a range of diseases. NCATS could be a terrific resource especially for rare diseases like neurofibromatosis, in particular if NCATS colalborates with foundations like CTF, as well as industry and the Food and Drug Administration - which is all part of the NCATS plan.
The webcast will be available in archive for viewing. More information: here.  

Last week, the Wall Street Journal reported on the FDA approval of the drug Benlysta as a treatment for lupus.  Lupus and NF are biologically very different but the approval of Benlysta can nevertheless prove instructive as we work to find treatments and a cure for NF.   

At first look the numbers are daunting.  GlaxoSmithKline, or more specifically its predecessor SmithKline Beecham, invested more than $125 million in research and development to bring Benlysta to the market.  GSK's investment came on the heels of hundreds of millions, if not billions, spent by Human Genome Sciences, who partnered with GSK in 2006 to help advance the project.   

To put those numbers in perspective, the Children's Tumor Foundation is the leading non-government funding source of NF research, last year we invested $4M in research into all of the manifestations of NF1, NF2, and schwannomatosis.  But while on the surface that number seems small it represents an investment of a far larger scope. 

Through our Research Advisory Board, our research programs seed-fund early stage ideas that go on to receive attention, and in many cases follow-on funding from biotech and pharmaceutical companies.  Further, our NF Preclinical Consortium and Clinical Trial & Research Awards test drugs that we acquire from biotech and pharma companies to prove safety and/or efficacy (including an on-going clinical trial on vestibular schwannomas with lapatanib, a drug provided by GlaxoSmithKline). 

In this way we engage companies, show them the potential for treatments in NF, and rapidly provide them with data to consider the opportunities of advancing the research and development of drugs.  Last year alone we partnered with Novartis, Genentech, Pfizer, Avila, AstraZeneca, and Merck, among other companies.  This year those partnerships will continue and expand as we search to find treatments for all of the manifestations of NF.

The Foundation is never going to be able to invest hundreds of millions of dollars to bring a drug from discovery to FDA approval.  That's not our role and that's not something non-profits are designed to do.  What we can do is leverage the commitment and resources of our supporters to provide information to companies that make each dollar we invest become many more in follow-on funding.  With your help we're succeeding in this realm like never before.

A major concern among young researchers is the gloomy prospect that when they are done with their Ph.D or MD training,  they won't be able to get funding to set up their own lab. This might include Children's Tumor Foundation Young Investigator Award recipients ready to become independent neurofibromatosis researchers. It is a worrying situation as young researchers are the 'seed corn' of science, ensuring  future continued research progress. Faced with the current financial situation, though, many young scientists leave scientific research for other career paths.   
To address this, and especially to ensure support for the brightest young stars, the National Institutes of Health is planning an Early Independence Award (EIA) that would allow researchers to move directly from completing their Ph.D or MD, and on to running an independent lab. 
At this time the NIH is asking for YOUR feedback and input on this proposed program. Deadline for feedback: March 18th. For more information and to offer your comments click here.

Pain can occur in all forms of neurofibromatosis, in particular, severe and untreatable pain is a hallmark of schwannomatosis, the rarest form of NF affecting an estimated one in every 40,000 individuals.  Pain is the most abstract of medical conditions. How can you describe it? And if you cannot describe it, how can a doctor prescribe treatment?  With this in mind, it is not surprising that 80% of pain sufferers never receive effective therapy. The February 24 issue of Time takes on the pain issue in an article that highlights potential new effective pain interventions. Brain imaging studies suggest that chronic pain can lead to permanent structural changes in the nervous system, and the common use of opioids to treat pain taps into the brain’s ‘addictive’ circuits which is why these drugs can become difficult to stop taking.  One approach being pursued is biofeedback, which is essentially ‘training’ the brain to think of more pleasant things when suffering pain, this has shown some positive results.  Magnet therapy has also been used to treat pain, using technology drawn from treatment of bipolar disorder.

One interesting aspect of pain in schwannomatosis is that it does not necessarily occur in the same site as the tumors are present.  This 'displaced' pain is also the case in phantom limb syndrome where pain is felt even when the appendage is gone. In phantom limb pain this trait has been attributed to excessively high level of signalling of a growth factor called brain derived neurotrophic factor (BDNF).  Ongoing Children’s Tumor Foundation-funded research in the lab of Dr. Larry Sherman at Oregon Health Sciences University is testing the theory that BDNF signalling is also hyperactive in mice that have schwannomatosis related pain. With funding from CTF's Schwannomatosis Awards and Drug Discovery Initiative programs, Dr. Sherman has developed the first ever genetic mouse model of schwannomatosis pain, and is testing drugs from Pfizer and AstraZeneca that target BDNF signaling to see if this will block the pain in the mice. Results are expected later this year.

Ed note: the following article can be found in the forthcoming NF News, the newsletter of the Children's Tumor Foundation, if you'd like to be added to our mailing list please contact ggleeson@ctf.org. 

Jack Burke wants to be the busiest man in the world. That may seem like a tall order for a six-year-old but it doesn’t deter this NF Hero whose desired future professions range from doctor to actor.

Despite his audacious ambitions and upbeat attitude Jack hasn’t had the easiest early years. Diagnosed with NF1 at two-years old due to café-au-lait spots and vision difficulties it was later discovered that Jack had a plexiform neurofibroma on his left eye orbit. Jack’s parents, Beth and Jake, have him monitored regularly by physicians and work hard to ensure he receives the very best care. But they’ve also taken to building the NF community in their hometown of Atlanta and raising funds for research.

“When we first got the diagnosis we didn’t know what to expect,” said Beth. “We kept it close to our vest and didn’t tell a lot of people. Then we realized the only way we could cure our hopelessness and helplessness was to do something about it."

Beth contacted Stephanie Yolish at the Foundation and the two began planning a symposium at Children's Hospital of Atlanta. They invited Dr. Bruce Korf and sent a mass email to area families affected by NF. More than 100 people gathered for what
was an eye-opening experience, both in terms of what was learned and in terms of how vast the community was.

“We were shocked at the response rate,” said Beth. “People were craving information and collective action. That day we started
building toward a more cohesive group.”

The symposium also motivated the Burkes to push forward with their fundraising activities. They signed-up Jack to be a Racing4Research NF Hero as a way to introduce him to NF and some of the others who live with the disorder, and to also give them a chance to raise money for research. Over the course of 2010 they hosted events and shared Jack’s story with friends and family.

“The response was amazing,” Jake said. “We learned that a lot of people are just looking to be asked to help.”

In total the Burkes raised more than $15,000 toward Jack’s NF Hero campaign and then they joined the Foundation in Daytona at the Rolex 24 where Jack had a chance to meet many other kids affected by NF.

“It was amazing on several levels,” said Jake of the R4R experience. “It was a great way to introduce Jack to a life of NF in a very positive and hopeful way. The empowerment that he got, when he stood in front of a room of 200 people and spoke into a microphone – it was a huge step.”

The experience also gave Jack the opportunity to practice his craft. Prior to the race each NF Hero gets to sign the #4 Children’s Tumor Foundation car and sit in the drivers seat for a photo op. The event draws a large media gathering with reporters and t.v. news crews wanting to get in on the action. Jack felt the experience was just like being a movie star, “there was nothing around me but cameras,” he said.

The Foundation is hopeful that he won’t be too busy to join us at the track again next year.