Data made available for Research Tools that Accelerate Development of Therapies for Neurofibromatosis Type 1 Plexiform Neurofibromas
For Release: October 2018
Development of therapies for human disease remains dependent on well-characterized and validated model systems. Slow growing histologically benign tumors such as neurofibromas are challenging to grow in typical culture conditions. As a result, the scientific field has been without reproducible, well-characterized cell culture model systems for neurofibromas.
Neurofibromas are tumors of the nerve that are found most commonly in people with neurofibromatosis type 1 (NF1). NF1 is a neurogenetic tumor syndrome with an estimated prevalence of 1/2500-1/3000. A type of neurofibroma called a plexiform neurofibroma affects up to 50% of people with NF1. These tumors can cause weakness, sensory changes, deformity, pain and have a notable risk of converting to a deadly sarcomas called malignant peripheral nerve sheath tumors (MPNST).
Recent advances in isolating the NF1 mutant Schwann cells, the cells that cause neurofibromas, from human samples, paired with techniques to maintain continuous passaging of these cells (a process called immortalization) and confirmation of their genetic signature at each stage in this process, now provides the research community with a new set of highly characterized tools for biologic discovery. A team of researchers from the University of Florida developed and characterized a set of immortalized, NF1 patient derived Schwann cells in an initial effort to create a series of cells that represent the genetic diversity of human plexiform tumors. This work is described in the manuscript “Immortalization of human normal and NF1 neurofibroma schwann cells”, Laboratory Investigation, 2016 Oct; 96:1105–1115. PMID: 27617404. Their reliability in the setting of high through-put drug screens has also recently been demonstrated in a large scale dose response-based screening study of well annotated drug candidates to allow pathway interrogation (Scientific Data June 12, 2018). This latter manuscript also describes genome-wide characterization of these cell lines.
All of the data generated from the above two manuscripts has now been made openly available and can be accessed and evaluated through the Synapse portal managed by Sage Bionetworks. Through making this genetic and molecular data openly available to the global research community, the investigators and sponsors hope to foster collaborations that will collectively advance efforts in developing effective therapies to prevent or treat neurofibromas. In addition, cell lines will be available via the biological materials resource and standards organization, ATCC (https://www.atcc.org).
This work was a major initiative of the Neurofibromatosis Therapeutic Acceleration Program (NTAP) (www.n-tap.org) based in The Johns Hopkins School of Medicine.
The Johns Hopkins University, and University of Florida, are academic institutions based respectively in Baltimore, Maryland, and Gainesville, Florida.
Sage Bionetworks is a nonprofit biomedical research organization, founded in 2009, with a vision to promote innovations in personalized medicine by enabling a community-based approach to scientific inquiries and discoveries. Sage Bionetworks strives to activate patients and to incentivize scientists, funders and researchers to work in fundamentally new ways in order to shape research, accelerate access to knowledge and transform human health. It is located in Seattle and is supported through a portfolio of philanthropic donations, competitive research grants, and commercial partnerships. More information is available at www.sagebionetworks.org.
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