Long-term Phase 1/2 intraspinal stem cell transplantation outcomes in ALS.

Area of Science:

• Neuroscience
• Regenerative Medicine
• Clinical Trials

Background:

• Intraspinal human spinal cord-derived neural stem cell (HSSC) transplantation is a potential therapy for amyotrophic lateral sclerosis (ALS).
• Previous clinical trials for HSSC transplantation in ALS have lacked adequate control groups.
• Post hoc analysis is crucial for informing future ALS clinical trial designs.

Purpose of the Study:

• To compare the efficacy of intraspinal HSSC transplantation in ambulatory limb-onset ALS participants against matched historical control datasets.
• To provide data for designing future randomized, sham surgery-controlled efficacy studies for HSSC transplantation in ALS.

Main Methods:

• A post hoc analysis comparing ambulatory limb-onset ALS participants from Phase 1 and 2 (Ph1/2) open-label HSSC transplantation studies with matched participants from the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) and ceftriaxone datasets.
• Assessment of survival, ALS Functional Rating Scale revised (ALSFRS-R), and a composite ALS/SURV statistic (combining survival and ALSFRS-R) over up to 3 years post-transplant.
• Matched participant subsets included: PRO-ACT (n=1108), Ph1/2 (n=21); ceftriaxone (n=177), Ph1/2 (n=20).

Main Results:

• Survival did not significantly differ between Ph1/2 cohorts and PRO-ACT or ceftriaxone cohorts (P > 0.88).
• Mean ALSFRS-R at 24 months was significantly higher in the Ph1/2 cohort compared to both PRO-ACT (30.1 vs. 24.0, P=0.048) and ceftriaxone (30.7 vs. 19.2, P=0.0023) cohorts.
• The composite ALS/SURV statistic indicated improved functional outcomes in the Ph1/2 cohort compared to historical controls at 24 months.

Conclusions:

• Comparison of Ph1/2 studies to historical datasets revealed significantly improved survival and function using ALS/SURV versus PRO-ACT controls.
• While results are encouraging, comparison against historical populations demonstrate limitations in noncontrolled studies.
• Findings support continued evaluation of HSSC transplantation in ALS and the necessity of control populations for future efficacy studies.