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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.

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.  

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.

For the second year in a row the Children's Tumor Foundation has published the Proceedings from the Neurofibromatosis Conference in the American Journal of Medical Genetics.  The NF Conference is the biggest annual international gathering of NF researchers and clinicians; this meeting has been hosted by CTF for over 25 years. The 2010 meeting in Baltimore, MD was our biggest ever, of over 300 attendees. The 2010 meeting highlights reported in AJMG include the latest updates on NF clinical trials, diagnosis and care; as well as the latest discoveries coming through the pipeline. You can read the 2010 NF Conference publication here. The 2011 NF Conference will be held in Jackson Hole, WY June 11-14. NF researchers and clinicians wishing to attend should click here for more information.