Neurologic Stem Cell Treatment Study (NEST) using bone marrow derived stem cells for the treatment of neurological disorders and injuries: study protocol for a nonrandomized efficacy trial

Abstract

Background: A large number of approximately 600 known neurological diseases have no or limited medical interventions; many treatments are temporizing or only marginally effective and have changed little over decades. The Neurologic Stem Cell Treatment Study (NEST) utilizes bone marrow derived stem cells (BMSCs) for neurological diseases and injuries to nervous tissue. Methods/Design: Administration of BMSCs is an established approach for the treatment of neurological diseases and injury with its effectiveness verified in the pre-clinical and clinical studies. BMSCs and the associated bone marrow fraction are posited to have a number of different mechanisms by which they may potentially improve neurological function. The circumventricular organs which lie in the wall of the third ventricle are noteworthy for a minimized or absent blood-brain barrier (BBB) facilitating entry of intravenously provided BMSCs. There is documentation in the literature that intranasal delivery of BMSCs may follow the pathways of the trigeminal nerves, facilitating their entry into the pons, brain parenchyma and cerebral spinal fluid (CSF) for effects on the CNS. The NEST is an open label, non-randomized, efficacy study with two arms. Arm 1 consists of intravenous autologous BMSCs alone; Arm 2 combines intravenous with intranasal application of BMSCs to the lower 1/3 of the nasal mucosa. There will be a total of 300 patients in the study. Endpoints include at least a 10% improvement in neurological function. Discussion: There have been a number of preclinical studies establishing the utility of intravenous and intranasal methods in providing access to the CNS for certain drugs, proteins and cellular elements. Preclinical and clinical studies utilizing BMSCs have shown positive effects in various neurological diseases. It is anticipated that combining these two administration methods for BMSCs delivery to the brain may provide a greater therapeutic response. Trial registration: ClinicalTrials.gov identifier NCT02795052; registered on June 6, 2016. Ethics: This study protocol has been Institutional Review Board (IRB) approved and will be performed in accordance with principles of research ethics set forth in the Belmont Report. Informed consent: Signed informed consent will be obtained from the patients or their guardians.