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. 2024 May 24;12(6):1162.
doi: 10.3390/biomedicines12061162.

Non-Invasive Spinal Cord Stimulation for Motor Rehabilitation of Patients with Spinal Muscular Atrophy Treated with Orphan Drugs

Anton Novikov  1 , Maria Maldova  1 , Natalia Shamantseva  2 , Ivan Shalmiev  1 , Elena Shoshina  1 , Natalia Epoyan  1 , Natalia Krutikova  1 , Tatiana Moshonkina  2
Affiliations

Non-Invasive Spinal Cord Stimulation for Motor Rehabilitation of Patients with Spinal Muscular Atrophy Treated with Orphan Drugs

Anton Novikov et al. Biomedicines. .

Abstract

Spinal muscular atrophy (SMA) is an orphan disease characterized by the progressive degeneration of spinal alpha motor neurons. In recent years, nusinersen and several other drugs have been approved for the treatment of this disease. Transcutaneous spinal cord stimulation (tSCS) modulates spinal neuronal networks, resulting in changes in locomotion and posture in patients with severe spinal cord injury and stroke. We hypothesize that tSCS can activate motor neurons that are intact and restored by medication, slow the decline in motor activity, and contribute to the development of motor skills in SMA patients. Thirty-seven children and adults with SMA types 2 and 3 participated in this study. The median duration of drug treatment was over 20 months. The application of tSCS was performed during physical therapy for 20-40 min per day for ~12 days. Outcome measures were specific SMA motor scales, goniometry of contractured joints, and forced vital capacity. Significant increases in motor function, improved respiratory function, and decreased contracture were observed in both type 2 and 3 SMA participants. The magnitude of functional changes was not associated with participant age. Further studies are needed to elucidate the reasons for the beneficial effects of spinal cord electrical stimulation on SMA.

Keywords: nusinersen; onasemnogene abeparvovec; physical therapy; risdiplam; spinal cord stimulation; spinal muscular atrophy.

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Conflict of interest statement

N.K. is a researcher on the study team and holds shareholder interest in EIRMed. T.M. is a researcher on the study team and holds shareholder interest in Cosyma. She holds certain inventorship rights on intellectual property licensed by Cosyma. The remaining authors declare no conflicts of interest. The funder had no role in the design of this study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Pre-treatment demographic and clinical data of SMA participants. SMA2 and SMA3—SMA type 2 and 3 participants, respectively. (a) Age; (b) upper limb function as measured using the Revised Upper Limb Module scale (RULM); (c) physical abilities as measured using the Hammersmith Function Motor Scale Expanded (HFMSE); (d) pulmonary function as measured using Forced Vital Capacity (FVC); (e) knee range of motion (ROM), left and right leg results combined. The crosses are averages, the circles are data points. *, **, and ***—p < 0.05, p < 0.01, and p < 0.001, respectively, as measured using the Mann–Whitney test. #—p < 0.05 as measured using Student’s t-test.
Figure 2
Figure 2
Changes in the Revised Upper Limb Module scale (RULM) score after tSCS course in SMA type 2 and 3 participants ((a) and (b), respectively). One line—one participant. Dotted lines—adult patients. One SMA type 2 participant and seven SMA type 3 participants showed a maximum score of 37 before and after tSCS sessions. Their results are not shown because the score does not change after the sessions. (c)—Difference in RULM score after the sessions in SMA type 2 and type 3 groups. The crosses are averages, the circles are data points. **—p < 0.01 as measured using the paired Wilcoxon test.
Figure 3
Figure 3
Changes in the Hammersmith Function Motor Scale Expanded (HFMSE) score after tSCS course in SMA type 2 and 3 participants ((a) and (b), respectively). One line—one participant. Dotted lines—adult patients. (c)—Difference in HFMSE score after the sessions in SMA type 2 and type 3 groups. The crosses are averages, the circles are data points. ***—p < 0.001 as measured using the paired Wilcoxon test.
Figure 4
Figure 4
Change in pulmonary function (Forced Vital Capacity, FVC) after tSCS course in SMA type 2 and 3 participants ((a) and (b), respectively). One line—one participant. Dotted lines—adult patients. (c)—Difference in FVC after the sessions in SMA type 2 and type 3 groups. The crosses are averages, the circles are data points. **—p < 0.01 as measured using the paired Wilcoxon test.
Figure 5
Figure 5
Change in knee range of motion (ROM) after tSCS treatment in SMA type 2 and 3 participants ((a) and (b), respectively) with pre-treatment knee contractures. Right and left knee ROM results are combined. One line—one participant. Dotted lines—adult patients. (c)—Difference in ROM after the course of treatment in SMA type 2 and type 3 groups. The crosses are averages, the circles are data points. *** and **—p < 0.0001 and p < 0.01, respectively, as measured using the paired Wilcoxon test.
Figure 6
Figure 6
Comparison of differences in outcomes between non-sitters (n-s) and sitters (s). (a) Revised Upper Limb Module scale (RULM); (b) Hammersmith Function Motor Scale Expanded (HFMSE); (c) Forced Vital Capacity (FVC); (d) knee range of motion (ROM), combined left and right leg results. The crosses are averages, the circles are data points. *, **, and ***—p < 0.05, p < 0.01, and p < 0.001, respectively, as measured using the paired Wilcoxon test. &—p < 0.05 as measured using the Mann-Whitney test.
Figure 7
Figure 7
Comparison of differences in outcomes between adults and children in the SMA type 3 group. (a) Revised Upper Limb Module scale (RULM); (b) Hammersmith Function Motor Scale Expanded (HFMSE); (c) Forced Vital Capacity (FVC); (d) knee range of motion (ROM), combined left and right leg results. The crosses are averages, the circles are data points.
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