Neurofibromatosis
Prof C O Hanemann
Peninsula Medical School, Plymouth
2008 – 2011 Research Assistant
A primary human in vitro model to test and translate new therapies for Neurofibromatosis type 2 tumours into clinical trials.
Prof C Oliver Hanemann is Professor of Clinical Neurobiology and Honorary Consultant Neurologist at the Peninsula Medical School, Plymouth.
Neurofibromatosis type 2 (NF2) is a hereditary disorder characterised by development of multiple tumours in the nervous system such as schwannomas, meningiomas and ependymomas. NF2 usually manifests early and is regarded as a childhood disease. All NF2 tumours are caused by mutations in a gene coding for the tumour suppressor merlin. Tumours caused by mutations in the merlin gene are genetically well defined and frequent. As these tumours grow slowly, classical chemotherapeutic treatments are not effective. The huge tumour load in NF2 is an additional therapeutic problem, leading to increased morbidity and reduced life expectancy.There is great medical need to find new therapies for these tumours.
Currently transgenic mice and xenotransplantation of tumours into nude mice are used by most researchers to test pharmaceutical compounds for tumours caused by mutation in the NF2 gene. Mice are also widely used to prepare Schwann cells for in vitro experiments. However, there are limitations to using mice, for example transgenic mice do not replicate the genetic situation in the human disease and xenotransplants have an altered blood supply.
The use of a human in vitro model to test and translate new therapies of NF2 tumours into clinical trials would potentially replace many animal experiments. Prof Oliver Hanemann has already developed a human schwannoma in vitro model using primary human cells [1, 2]. Dr Hadwen Trust funding will be used to support the further development of this human model by investigating signalling pathways in detail to try to isolate relevant molecules that might be blocked by drugs.
An integral part of Prof Hanemann’s research strategy is to test drugs that are already in clinical use for other diseases, mostly other cancers, or new compounds that are in the development pipeline. Re-profiling available drugs using the human in vitro model could allow translation into clinical trials without lengthy animal testing.
Reference
1. Rosenbaum C, Kluwe L, Mautner VF et al (1998). Isolation and characterization of Schwann cells from neurofibromatosis type 2 patients. Neurobio Dis 5:55-64.
2. Rosenbaum T, Rosenbaum C, Winner U et al (2000). Long-term culture and characterization of human neurofibroma-derived Schwann cells. J Neurosci Res 61:524-532.
3. Hanemann CO (2008). Magic but treatable? Tumours due to loss of Merlin. Brain 131:606-615.