Intrathecal administration of mesenchymal stem cells in patients with adrenomyeloneuropathy

Tomasz Siwek; Beata Zwiernik; Katarzyna Jezierska-Woźniak; Kamila Jezierska; Marcin P Mycko; Krzysztof W Selmaj

doi:10.3389/fneur.2024.1345503

Intrathecal administration of mesenchymal stem cells in patients with adrenomyeloneuropathy

Front Neurol. 2024 Feb 2:15:1345503. doi: 10.3389/fneur.2024.1345503. eCollection 2024.

Authors

Tomasz Siwek^{1

2}, Beata Zwiernik^{1

2}, Katarzyna Jezierska-Woźniak³, Kamila Jezierska², Marcin P Mycko^{1

2}, Krzysztof W Selmaj^{1

4}

Affiliations

¹ Department of Neurology, University of Warmia and Mazury in Olsztyn, Olsztyn, Poland.
² University Hospital, University of Warmia and Mazury in Olsztyn, Olsztyn, Poland.
³ Laboratory for Regenerative Medicine, Department of Neurosurgery, University of Warmia and Mazury in Olsztyn, Olsztyn, Poland.
⁴ Center of Neurology, Lodz, Poland.

Abstract

Background and objectives: X-linked adrenomyeloneuropathy (AMN) is an inherited neurodegenerative disorder associated with mutations in the ABCD1 gene and the accumulation of very long-chain fatty acids (VLFCAs) in plasma and tissues. Currently, there is no effective treatment for AMN. We have aimed to evaluate the therapeutic effects of mesenchymal stem cell (MSC) transplantation in patients with AMN.

Methods: This is a small cohort open-label study with patients with AMN diagnosed and treated at the University Hospital in Olsztyn, Poland. All patients met clinical, biochemical, MRI, and neuropsychological criteria for AMN. MSCs derived from Wharton jelly, 20 × 10⁶ cells, were administered intrathecally three times every 2 months, and patients were followed up for an additional 3 months. The primary outcome measures included a blinded assessment of lower limb muscle strength with the Medical Research Council Manual Muscle Testing scale at baseline and on every month visits until the end of the study. Additional outcomes included measurements of the timed 25-feet walk (T25FW) and VLFCA serum ratio.

Results: Three male patients with AMN with an age range of 26-37 years participated in this study. All patients experienced increased muscle strength in the lower limbs at the end of the study versus baseline. The power grade increased by 25-43% at the baseline. In addition, all patients showed an improvement trend in walking speed measured with the T25FW test. Treatment with MSCs in patients with AMN appeared to be safe and well tolerated.

Discussion: The results of this study demonstrated that intrathecal administration of WJ-MSC improves motor symptoms in patients with AMN. The current findings lend support to the safety and feasibility of MSC therapy as a potentially viable treatment option for patients with AMN.

Keywords: AMN; WJ-MSC; adrenomyeloneuropathy; mesenchymal stem cells; motor function.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by the internal grant of the University of Warmia and Mazury in Olsztyn as well as by the Minister of Science Poland under “the Regional Initiative of Excellence Program”.