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Innovative nerve sheath tumor therapy

Dr Alexander Schulz, Leibniz Institute on Aging - Fritz-Lipmann-Institute e.V. (FLI); Dr Helen Morrison, Leibniz Institute on Aging - Fritz-Lipmann-Institute e.V. (FLI)



Nerve sheath tumors like schwannomas, appear sporadically and in association with genetic syndromes such as Neurofibromatosis type 1 (NF1), also known as von Recklinghausen Disease, Neurofibromatosis type 2 (NF2) or Schwannomatosis (NF3). Despite their predominantly benign nature, these tumors often have a devastating impact on patients' life quality, as treatment options are mostly limited to tumor resection by surgery endangering long-term nerve functionality. In case of NF2 related schwannomas this often means lifelong deafness as the tumors predominantly appear at the vestibulocochlear nerve. Since patients affected by nerve sheath neoplasms will develop multiple tumors over their lifetime there is a need for an alternative therapy.


The invention relates to the use of the epidermal growth factor (EGF)-like domain of neuregulin (NRG)-1 as a medicament in the treatment and prevention of nerve sheath tumors. NRG proteins 1 to 4 belong to the family of EGF and comprise an EGF-like domain. These proteins have diverse functions in the development of the nervous system. In a Schwannoma mouse model the soluble EGF-like domain of NRG1 effectively inhibits the growth of tumors of the nerve sheath after systemic as well as local application of the molecule. The EGF-like domain of NRG1 may act as a differentiation inducer on tumor cells of the nervous system. By differentiation of the tumor cells the proliferation rate can be reduced and tumor growth efficiently stopped or even reversed. Recombinant EGF-like domain of NRG1 is currently under clinical development for treatment of cardiovascular diseases and proved to be safe in phase II clinical trials in humans.

Commercial Opportunity

Development of a protein replacement therapy based on NRG1 for treatment of nerve sheath tumors. The technology is offered for co-development and/or licensing.

Development Status

Proof of concept obtained in a Schwannoma mouse model. Efficacy studies in different Neurofibromatosis NF1- and NF2-mouse models confirm proof of concept.

Patent Situation

European priority application filed in 2016, international PCT-application pending (WO2017182500).

Further Reading

Schulz et al. 2016. The importance of nerve microenvironment for schwannoma development. Acta Neuropathologica 132 (2):289–307.Schulz et al. 2014. A neuronal function of the tumor suppressor protein merlin. Acta Neuropathologica Communications 2:82. Schulz et al. 2014. Neuronal merlin influences ERBB2 receptor expression on Schwann cells through neuregulin 1 type III signaling. Brain 137:420-432.


Innovative nerve sheath tumor therapy

Neurofibromatosis type 2 (NF2) – vestibular schwannoma; MRT of the head of a NF2 mouse, the white region on the right hand side represents the tumor located at the inner auditory canal attached to the vestibularis nerve.