Multiple Sclerosis

Symptom improvements were most notable 1 month after treatment. Improvements were seen in EDSS scores (p<=0.03), as well as in bladder, bowel, and sexual dysfunction (p<=0.01), in non-dominant hand average scores (p<=0.01), in walk times (p<=0.02) and general perspective of a positive health change and improved quality of life. MRI scans of the brain and the cervical spinal cord showed inactive lesions in 15/18 (83.3%) subjects after 1 year.

The treatment protocol was well tolerated by patients. There was an overall trend of improvement in all the tests, except the lesion volume which increased significantly. A decrease of 4 and 3.5 points on the EDSS was achieved in two patients. We report a correlation between a decreased lesion number at baseline and higher IL-6, IL-8, and VEGF MSC-CM content.

Nineteen percent of treated participants achieved pre-specified ⩾ 25% improvements in timed 25-foot walk speed/nine-HPT at 28 weeks compared to baseline, along with consistent efficacy signals for pre-specified response criteria across other secondary efficacy outcomes. CSF neuroprotective factors increased, and inflammatory biomarkers decreased after treatment, consistent with the proposed mechanism of action.

Thirty-four patients underwent lipectomy for AdMSCs collection, were randomized and thirty were infused (11 placebo, 10 low-dose and 9 high-dose); 4 randomized patients were not infused because of karyotype abnormalities in the cell product. Only one serious adverse event was observed in the treatment arms (urinary infection, considered not related to study treatment). No other safety parameters showed changes. Measures of treatment effect showed an inconclusive trend of efficacy.

Post-infusion, no change was detected in measures of corticomotor excitability or measures of intra- or interhemispheric inhibition. The latency of motor evoked potentials and central motor conduction time were significantly prolonged. These changes in motor conduction were associated with declines in hand dexterity post-infusion.

After 6 months of MSC-IT treatment, CSF levels of NF-L significantly decreased compared to baseline (P = .026). 9 out of 15 patients had a reduction in NF-L levels of over 50% compared to 5 out of 15 in the MSC-IV group and 1 out of 15 in the placebo group (P = .001 for MSC-IT vs. placebo). CXCL13 levels were also reduced but not significantly.

21 patients had mild injection-related adverse effects, such as fever, and 15 experienced headaches. No major adverse effects were reported during follow-up. MRI showed the possible migration of MSCs in the meninges, subarachnoid space, and spinal cord. The ALSFRS score remained stable, while the EDSS score improved. Immunological analysis indicated an increase in regulatory T cells and a decrease in lymphocyte response. Myeloid dendritic cells also showed changes after MSC transplantation.

MSC-NP treatment was safe and well tolerated. The 20 enrolled subjects completed all 60 planned treatments without serious adverse effects. Minor adverse events included transient fever and mild headaches usually resolving in <=24 h. Post-treatment disability score analysis demonstrated improved median EDSS suggesting possible efficacy. Positive trends were more frequently observed in the subset of SPMS patients and in ambulatory subjects (EDSS ≤ 6.5). In addition, 70% and 50% of the subjects demonstrated improved muscle strength and bladder function, respectively, following IT MSC-NP treatment.