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Viral Oncolytic Therapeutics for Neoplastic Meningitis

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Technical Report,01 Jul 2011,30 Jun 2014

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Massachusetts General Hospital Boston United States

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The goal of this collaborative exploratory project is to develop novel, safe and efficient therapy for neoplastic meningitis meningeal metastasis of breast cancer. The proposed therapy will be based on direct intrathecal administration of oncolytic viruses into the cerebrospinal fluid CSF. During the first research year, physiology of the intrathecal delivery of particles was studied in rats. The data was compared with the results obtained in non-human primates in our parallel studies. The key findings are the following. 1 The key factor defining the patterns of the initial particle distribution between the cerebral and spinal CSF is the volume of the bolus. 2 The key physiological factors defining further transport of the particles in the leptomeningeal space and further into perivascular spaces are tissue pulsation and particle interaction with the arachnoid. The data of the functional investigation of the diameter of meningeal pores draining CSF to the systemic circulation suggests a new, previously unreported subset of leptomeningeal pores that require further investigation. The new mechanistic model of particle transport in the leptomeningeal space supports the initial idea of the study and suggests further development of therapies for neoplastic meningitis based on oncolytic viruses.

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