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Int J Med Sci 2020; 17(13):1927-1935. doi:10.7150/ijms.47002 This issue Cite

Research Paper

Articulation recovery in ALS patients after lineage-negative adjuvant cell therapy - preliminary report

Wioletta Pawlukowska^1✉*, Bartłomiej Baumert^2*, Monika Gołąb-Janowska³, Ewa Pius-Sadowska⁴, Zofia Litwińska⁵, Maciej Kotowski⁶, Agnieszka Meller⁷, Iwona Rotter⁸, Jarosław Peregud-Pogorzelski⁹, Przemysław Nowacki¹⁰

1. Department of Medical Rehabilitation and Clinical Physiotherapy, Pomeranian Medical University, Szczecin, Poland.
2. Department of General Pathology, Pomeranian Medical University, Szczecin, Poland.
3. Department of Neurology, Pomeranian Medical University, Szczecin, Poland.
4. Department of General Pathology, Pomeranian Medical University, Szczecin, Poland.
5. Department of General Pathology, Pomeranian Medical University, Szczecin, Poland.
6. Department of General Pathology, Pomeranian Medical University, Szczecin, Poland.
7. Department of Neurology, Pomeranian Medical University, Szczecin, Poland.
8. Department of Medical Rehabilitation and Clinical Physiotherapy, Pomeranian Medical University, Szczecin, Poland.
9. Department of Paediatric Oncology, Pomeranian Medical University, Szczecin, Poland.
10. Department of Neurology, Pomeranian Medical University, Szczecin, Poland.
*These authors equally contributed to the work.

✉ Corresponding author: Wioletta Pawlukowska, PhD. Department of Medical Rehabilitation and Clinical Physiotherapy, Department of Neurology, Pomeranian Medical University; Address: Żołnierska 54, 71-210 Szczecin. Tel.: +48 914800914; Fax +48 914800918; E-mail: wpawlukoedu.pl. More

Abstract

Background: Amyotrophic lateral sclerosis (ALS) is one of the most frequently occurring neurodegenerative diseases affecting speech and swallowing. This preliminary study aimed to investigate whether an autologous lineage-negative stem/progenitor cell therapy applied to ALS patients affects the level of selected trophic and proinflammatory factors, and subsequently improves the articulation.

Methods: We enrolled 12 patients with sporadic ALS, who underwent autologous bone marrow-derived lineage negative (LIN^-) cells administration into cerebrospinal fluid (CSF). We evaluated patients' articulation using the Frenchay Dysarthria Assessment on days 0 and 28 following the LIN^- cells administration. Concentrations of various factors (BDNF, NGF, ANGP-2, VEGF, PDGF-AA, PEDF, COMP-FH, CRP, C3, C4) in CSF were quantified by multiplex fluorescent bead-based immunoassays in the samples collected on the day of LIN^- cells administration and 28 days later. On top of this, we assessed levels of BDNF and NGF in the patients' plasma on the day of the injection, three, seven days and three months after the treatment.

Results: Of the 12 patients who received the LIN^- cell therapy 8 showed short-termed improvement in articulatory functions (group I), which was particularly noticeable in better phonation time, lips and soft palate performance, swallowing reflex and voice loudness. Four patients (group II) did not show substantial improvement. CSF concentrations of BDNF, ANGP-2 and PDGF-AA in group I decreased significantly 28 days after LIN^- cells administration. The highest concentration levels of BDNF in group II and NGF in both groups in blood plasma were observed on day 3 following the injection.

Conclusions: The outcomes of the LIN^- cell application in ALS treatment of articulatory organs are promising. The procedure proved to be safe and feasible. A short-lasting trophic effect of autologous LIN^- administration could encourage repeated cell's application in order to sustain their beneficial effects, however this approach needs further investigation.

Keywords: dysarthria, amyotrophic lateral sclerosis, speech disorders, LIN^- stem/progenitor cells, neurotrophins

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