The following was written by CTF Chief Scientific Officer Dr. Kim Hunter-Schaedle:
Earlier this week the Children’s Tumor Foundation hosted a workshop/think tank convening 25 international researchers and clinicians to review recent progress in schwannomatosis research and clinical management, and set priorities to advance future progress. The meeting was planned and chaired by Dr. Scott Plotkin (Harvard/MGH), Dr. Marco Giovannini (House Research Institute) and Dr. Gareth Evans (University of Manchester) and included updates on genetics, cell biology, surgical intervention and the potential of advancing to clinical drug therapies for schwannomatosis, the rarest form of neurofibromatosis affecting an estimated 1:40,000 persons.
In part through CTF funded projects, significant progress has been made since the gene SMARCB1 (also known as INI-1) was in 2007 identified as a causal factor in inherited schwannomatosis. Researchers have further unraveled the genetics of schwannomatosis, and learned that while SMARCB1 is important in inherited cases of schwannomatosis, this disease onset also involves the NF2 gene; and that in spontaneous (non-inherited) cases, SMARCB1 is not necessarily involved but that there are as yet unidentified genes involved. The first mouse models of schwannomatosis tumors and pain are now developed and being used to study tumor and pain biology and test drug therapies. And an international schwannomatosis database is established to collect information on schwannomatosis patients worldwide and facilitate future research projects and clinical trials.
At the workshop a series of priorities for the future was identified. There is a need to identify the additional genes and genetic modifiers that may be involved in interacting with the SMARCB1 or NF2 genes to lead to schwannomatosis. There is a need to develop more refined mouse models that represent schwannomatosis seen in humans as closely as possible, so that these can be used to study biology and tumor growth/pain and to test candidate drug treatments. The biology and mechanisms of pain – which is such a central and poorly understood element of schwannomatosis – need to be unraveled and understood. In terms of candidate drug therapies, it is rational to look at those drugs that are showing promise in mouse models of NF2 tumors, and see if they have impact on the tumors in mouse models of schwannomatosis.
Very importantly, now that we have a patient database, there is a need to plan clinical research studies to better understand schwannomatosis, such as understanding how individual patients condition has progressed following surgery, especially multiple surgeries; identifying whether there are blood-based or other biomarkers of schwannomatosis; and developing a pain survey for patients to better define the type and range of pain seen in schwannomatosis.; and looking ahead, prospective studies monitoring patients from time of diagnosis ongoing such as by whole body MRI. It is considered to be premature to consider clinical trials for schwannomatosis as we don’t have sufficient knowledge to do this; but that for patients in states of extreme crisis, there is the potential to begin testing drugs such as bevacizumab (Avastin) that have shown promise in NF2 patients.
Finally the clinical diagnostic guidelines for schwannomatosis were published in 2005 and the group reviewed these and made some recommendations to update these based on new genetics and clinical knowledge.
As a follow up to this workshop CTF will be spearheading the publication of a meeting report summarizing the latest update and recommendations for schwannomatosis. Also – in the next month – CTF will be releasing a Request for Applications to fund further schwannomatosis research. After this great meeting we look forward to seeing further research progress.
