Umbilical Cord Mesenchymal Stem Cells in Amyotrophic Lateral Sclerosis: an Original Study

Monika Barczewska, Stanisław Maksymowicz, Izabela Zdolińska-Malinowska, Tomasz Siwek, Mariusz Grudniak, Monika Barczewska, Stanisław Maksymowicz, Izabela Zdolińska-Malinowska, Tomasz Siwek, Mariusz Grudniak

Abstract

Objective: Amyotrophic lateral sclerosis (ALS) is still incurable. Although different therapies can affect the health and survival of patients. Our aim is to evaluate the effect of umbilical mesenchymal stem cells administrated intrathecally to patients with amyotrophic lateral sclerosis on disability development and survival.

Methods: This case-control study involved 67 patients treated with Wharton's jelly mesenchymal stem cells (WJ-MSC). The treated patients were paired with 67 reference patients from the PRO-ACT database which contains patient records from 23 ALS clinical studies (phase 2/3). Patients in the treatment and reference groups were fully matched in terms of race, sex, onset of symptoms (bulbar/spinal), FT9 disease stage at the beginning of therapy and concomitant amyotrophic lateral sclerosis medications. Progression rates prior to treatment varied within a range of ± 0.5 points. All patients received three intrathecal injections of Wharton's jelly-derived mesenchymal stem cells every two months at a dose of 30 × 106 cells. Patients were assessed using the ALSFRS-R scale. Survival times were followed-up until March 2020.

Results: Median survival time increased two-fold in all groups. In terms of progression, three response types measured in ALSFRS-R were observed: decreased progression rate (n = 21, 31.3%), no change in progression rate (n = 33, 49.3%) and increased progression rate (n = 13, 19.4%). Risk-benefit ratios were favorable in all groups. No serious adverse drug reactions were observed.

Interpretation: Wharton's jelly-derived mesenchymal stem cells therapy is safe and effective in some ALS patients, regardless of the clinical features and demographic factors excluding sex. The female sex and a good therapeutic response to the first administration are significant predictors of efficacy following further administrations. Graphical Abstract Medical therapeutic experiment with retrospective case-control analyses.

Keywords: ALS; Amyotrophic lateral sclerosis; Medical experiment; Progression rate; Survival; Umbilical cord; WJ-MSC.

Conflict of interest statement

Instytut Terapii Komórkowych S.A. (ITK) in Olsztyn is a private medical institution specialized in innovative commercial therapy which uses MSC. The Institute is partially owned by the University of Warmia and Mazury and controlled by Polski Bank Komórek Macierzystych S.A. (PBKM). M.B., S.M. and T.S. are employees of the Instytut Terapii Komórkowych S.A. I.Z.-M. and M.G. are employees of the Polski Bank Komórek Macierzystych S.A. The management of the ITK and PBKM had no influence on the collection, analysis and interpretation of data.

Figures

Graphical Abstract
Graphical Abstract
Medical therapeutic experiment with retrospective case-control analyses
Fig. 1
Fig. 1
Overall survival in (a) the general study population, b patients with decreased progression rate, c patients with no change in progression rate, d more advanced patients, e less advanced patients
Fig. 2
Fig. 2
a ALSFRS-R total score in the subgroups divided by clinical response. b: ALSFRS-R cumulative change in the subgroups divided by clinical response. T - treatment group; R - reference group; MSC administrations are marked with arrows

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