Neural stem cell transplantation in patients with progressive multiple sclerosis: an open-label, phase 1 study

Abstract

Innovative pro-regenerative treatment strategies for progressive multiple sclerosis (PMS), combining neuroprotection and immunomodulation, represent an unmet need. Neural precursor cells (NPCs) transplanted in animal models of multiple sclerosis have shown preclinical efficacy by promoting neuroprotection and remyelination by releasing molecules sustaining trophic support and neural plasticity. Here we present the results of STEMS, a prospective, therapeutic exploratory, non-randomized, open-label, single-dose-finding phase 1 clinical trial (NCT03269071, EudraCT 2016-002020-86), performed at San Raffaele Hospital in Milan, Italy, evaluating the feasibility, safety and tolerability of intrathecally transplanted human fetal NPCs (hfNPCs) in 12 patients with PMS (with evidence of disease progression, Expanded Disability Status Scale ≥6.5, age 18–55 years, disease duration 2–20 years, without any alternative approved therapy). The safety primary outcome was reached, with no severe adverse reactions related to hfNPCs at 2-year follow-up, clearly demonstrating that hfNPC therapy in PMS is feasible, safe and tolerable. Exploratory secondary analyses showed a lower rate of brain atrophy in patients receiving the highest dosage of hfNPCs and increased cerebrospinal fluid levels of anti-inflammatory and neuroprotective molecules. Although preliminary, these results support the rationale and value of future clinical studies with the highest dose of hfNPCs in a larger cohort of patients.

Mimicked Spinal Cord Fibers Trigger Axonal Regeneration and Remyelination after Injury

“…The cavity area of the A-DSCF/NPC group (0.4669 ± 0.02764 mm 2 ) and the A-CF/NPC group (0.6345 ± 0.1657 mm 2 ) was smaller, compared to the fiber group (Figure S9D in the Supporting Information). This may be related to the neuroprotective effects exerted by A-DSCF proteins and NPC. , …”

“…This may be related to the neuroprotective effects exerted by A-DSCF proteins and NPC. 80,81 The Basso−Beattie−Bresnahan (BBB) open-field locomotor test was conducted weekly to evaluate the motor function of rat hind limbs. After complete transection of SCI, the rats exhibited complete loss of motor function.…”

Role and limitation of cell therapy in treating neurological diseases

“…The experimental findings furnish evidence that the transplantation of NSCs is associated with a reduction in overall brain and gray matter volume loss 42 . Furthermore, the examination of untargeted proteomics and metabolomics in the cerebrospinal fluid of subjects subjected to NSC transplantation indicates that these cells operate as neuroprotective agents, functioning in nutrient provision and immune system regulation 43 …”

Repair what is lost: Neuroprotection through neural stem cells in progressive MS

“…In a recent issue of Nature Medicine , Genchi et al. 1 show the feasibility of neural stem cell transplantation in the STEMS trial. This is the first in-human phase 1 trial with intrathecally injected neuronal precursor cells (NPCs) from human fetal CNS (hfNPCs).…”

“… Genchi et al. 1 report the first phase 1 trial of neural stem cell transplantation in multiple sclerosis showing a reduction in gray matter atrophy. Results give hope for a new era of induced neuroprotection, especially in progressive multiple sclerosis.…”