Detailed demographics of the patients are shown in Table 2. The present clinical trial recruited 10 participants (8 males and 2 females) with an average age of 49.3 ± 21.2 years old. The severity of SCI was assessed using the modified Frankel classification, with 4 cases classified as B1 and 6 cases as B2. The neurological level of injury varied: 5 cases at C4, 1 case at C5, 3 cases at C6, and 1 case at C7. The types of spinal cord injuries included dislocation fractures in 5 cases, fractures in 2 cases and 3 cases without bony abnormalities. All the participants underwent surgical decompression and/or fixation. None of the patients received steroid administration.
All 10 participants received a single dose of allogenic CL2020 (15 × 106 cells corresponding to 2.1 to 2.7 × 105 cells/kg body weight) by intravenous drip. There were no cases in which Muse cell administration was discontinued during the procedure.
There were two reported severe adverse events. One patient showed mortality (10%) during the follow-up period, which was attributed to aspiration pneumonia. The participant developed aspiration pneumonia 60 days after CL2020 administration, and respiratory management was performed through endotracheal intubation and tracheostomy, along with antibiotic treatment. The symptoms were temporarily relieved, but the respiratory condition deteriorated again, leading to respiratory failure and death 193 days after treatment. Aspiration pneumonia related to the underlying condition, insufficient tidal volume due to thorax movement palsy caused by SCI, was determined to be the primary cause of death and was determined to have no causal relationship with Muse cell treatment.
Another patient had a urinary tract stone that needed surgical treatment. The patient was an 18-year-old man without a notable medical history who had a bladder stone on day 354 that needed endoscopic stone excision, probably because of the sequela of a neurogenic bladder and repeated urinary tract infection due to bladder palsy caused by SCI. Therefore, this event was also considered to be caused by an underlying condition unrelated to CL2020 administration.
The change in the ISNCSCI upper extremity motor score was 4.2 [1.0–7.4] (adjusted mean [95% CI]) at 4 weeks posttreatment (p = 0.016), 8.3 [5.3–11.2] at 12 weeks (p < 0.001), 8.4 [3.9–12.9] at 28 weeks (p = 0.002), and 8.3 [2.7–14.0] at 52 weeks (p = 0.009), showing statistically significant improvements at each time point compared to those data at the time of CL2020 administration (Fig. 1A). The change in the ISNCSCI lower extremity motor score (LEMS) showed significant improvement at 4 weeks post-treatment (p < 0.05) but did not show statistically significant improvements after subsequent time points compared to the time of CL2020 administration (Fig. 1B). The changes in the total ISNCSCI motor score were 7.7 [1.7–13.6] (p = 0.020), 13.6 [4.3–22.9] (p = 0.009), 14.8 [3.5–26.0] (p = 0.016), and 15.4 [2.3–28.5] (p = 0.026) at 4, 12, 24, and 52 weeks posttreatment, respectively, with statistically significant improvements at each time point compared to the time of CL2020 administration (Fig. 1C).
The change in the ISNCSCI sensory score (pinprick sensation) from the screening end was 9.5 [–4.6 to 23.6] at 4 weeks (p = 0.161), 22.9 [4.0 to 41.9] at 12 weeks (p = 0.023), 27.2 [7.3 to 47.1] at 28 weeks (p = 0.014), and 27.7 [6.5 to 48.8] at 52 weeks (p = 0.017), with statistically significant improvements after 12 weeks compared to the time of CL2020 administration. Light touch and pinprick showed statistically significant improvements at all time points except pinprick at 4 weeks compared to the time of CL2020 administration (Fig. 2A, B).
The change in the total score of the SCIM was 5.6 [from 2.3 to 8.9] at 4 weeks (p = 0.006), 4.2 [–2.2 to 10.5] at 12 weeks (p = 0.167), 14.6 [4.6 to 24.6] at 28 weeks (p = 0.011), and 17.8 [9.7 to 25.8] at 52 weeks (p = 0.002), with statistically significant improvements at all time points except 12 weeks (Fig. 3A).
The change in the quality-of-life (QOL) values evaluated with the EQ-5D did not show significant improvements at any time (Fig. 3B). By contrast, the change in the perception of current health status was 9.6 [–9.2 to 28.4] at 4 weeks (p = 0.268), 20.3 [2.3 to 38.3] at 12 weeks (p = 0.032), 31.7 [22.6 to 40.7] at 28 weeks (p < 0.001), and 34.8 [25.8 to 43.8] at 52 weeks (p < 0.001), with statistically significant improvements after 12 weeks compared to the time of CL2020 administration (Fig. 3C).
The modified Frankel classification showed an improvement of at least one grade in 6 of 10 participants at 28 weeks posttreatment and in 5 of 10 participants at 52 weeks posttreatment (evaluation was incomplete after 28 weeks for one participant who died due to aspiration pneumonia) (Fig. 4A, B).
Based on these findings, the administration of Muse cells to subacute phase cervical SCI was associated with improvements in functional impairment and QOL.