Harris VK, Vyshkina T, and Sadiq SA.
Cytotherapy. 2016;18(12): 1476-1482.
Background aims. There is a critical unmet need to develop regenerative therapies for the demyelinating disease multiple
sclerosis (MS).We previously characterized the immunoregulatory and trophic properties of neural progenitors derived from
bone marrow mesenchymal stromal cells (MSC-NPs) and established that cells derived from MS and non-MS patients
alike were therapeutically viable. In an experimental model of MS, intrathecal MSC-NP injection resulted in disease amelioration
with decreasedT-cell infiltration, and less severe lesion pathology associated with recruitment of resident progenitors
to inflammatory sites. In this pilot feasibility study, we investigated safety and dosing of intrathecal MSC-NP therapy in six
patients with MS. Methods. Patients with progressive MS and advanced disability who were refractory to all other conventional
MS treatments were enrolled in the study. For each dose, MSC-NP cells were cultured from autologous MSCs and
tested for quality control before intrathecal administration. Patients were evaluated for adverse events and neurological status
to assess safety of the treatment. Results. Six patients with progressive MS were treated with between 2 and 5 intrathecal
injections of escalating doses of autologous MSC-NPs and were followed an average of 7.4 years after initial injection.There
were no safety concerns noted, no serious adverse events, and the multiple dosing regimen was well tolerated. Four of the
six patients showed a measurable clinical improvement following MSC-NP treatment. Discussion. This pilot study supports
preliminary first-in-human safety and tolerability of autologous MSC-NP treatment for MS.