ClinicalTrials.gov Listings

Abstract

Background:

A significant number of the approximately 600 known neurologic diseases have no or limited medical interventions; many treatments are temporizing or only marginally effective and have changed little over decades. There have also been a number of journal reports of the benefits of treatment with bone marrow derived stem cells (BMSC) for diseases and damage to nervous tissue. Through the Neurologic Stem Cell Treatment study (NEST), the investigators hope to add to the volume of literature regarding the use of BMSC in those neurologic diseases and identify conditions likely to respond to this treatment.

Methods/Design:

Intravenous administration of BMSC is a well-established approach to neurologic disease and injury with much support for its effectiveness in the pre-clinical and clinical literature. BMSC and the associated bone marrow fraction are posited to have a number of different mechanisms by which they may potentially improve neurologic function. Within the diencephalon, there are specific circumventricular organs that lie in the wall of the third ventricle. These are noteworthy for a minimized or absent blood-brain barrier that facilitates their function of coordinating homeostatic mechanisms of the endocrine and nervous systems. Therefore, the investigators believe that the entry of BMSC and associated neurotrophic factors may be facilitated in these areas of the brain.

In addition to the use of intravenous BMSC, the NEST study will provide a treatment arm combining intravenous BMSC with application of BMSC to the cribriform plate in the upper nasal passages as a means of introducing BMSC to the central nervous system (CNS). There is significant documentation in the literature that intranasal delivery follows the pathways of both the olfactory and trigeminal nerves, facilitating entry into the parenchyma and cerebral spinal fluid (CSF) for effects on the CNS.

Discussion:

There have been a number of preclinical studies that have established the utility of both these methods in providing access to the CNS for certain drugs, proteins, and cellular elements. Similarly, both preclinical and clinical studies utilizing BMSC as well as other sources of mesenchymal stem cells have shown positive effects on various neurologic diseases. It is anticipated that combining these two administration methods for BMSC delivery to the brain may provide a greater therapeutic response.

Trial Registration: ClinicalTrials.gov; Identifier NCT02795052; Registered: June 6, 2016.

Ethics: This study protocol was Institutional Review Board (IRB) approved and will be performed in accordance with standard international research accords.

Informed Consent: Signed informed consent will be obtained from the patients or their guardians.