Autologous SVF therapy modulates neuroinflammation in ALS: phase I trial demonstrating safety and CSF biomarker...

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with limited treatments. Stromal vascular fraction (SVF), a cell population derived from autologous adipose tissue, exhibits multimodal immunomodulatory and neuroprotective properties, positioning it as a promising therapeutic candidate.

This trial aimed to assess autologous stromal vascular fraction (SVF) safety and efficacy in patients with ALS. 26 patients received combined intravenous (0.5 × 106 cells/kg) and intrathecal (20 × 10⁶ cells) autologous SVF (An exploratory second dose of SVF was administered intrathecally to three patients 45 days later). The trial is registered with the Chinese Clinical Trial Registry (ChiCTR2400091754).

SVF administration was well-tolerated. Five mild adverse events (adverse events, AEs) (subcutaneous bleeding, headache, and low-grade fever) occurred, with no serious AEs reported. Although ALSFRS-R scores showed non-significant improvement post-treatment, 15/26 participants (57.7%) self-reported symptomatic improvement after treatment. Critically, cerebrospinal fluid biomarker analysis revealed significant reductions in neurofilament light chain (NfL; Δ530.29 pg/mL, P = 0.039) and glial fibrillary acidic protein (GFAP; Δ622.23 pg/mL, P = 0.038), indicating attenuation of neuroaxonal degeneration and astroglial activation. While ALSFRS-R scores showed no significant change (Δ-0.53, P = 0.384), prognostic modeling identified female sex (OR = 0.011, P = 0.008) and shorter disease duration (OR = 1.35/month, P = 0.005) as predictors of response. Three patients who underwent the second treatment were well tolerated without any adverse events.

These findings indicate that Autologous SVF therapy might possess an acceptable safety profile for patients with ALS. The significant reduction in CSF NfL and GFAP levels provides objective evidence of their potential neuroprotective effects that modulates ALS-relevant neuroinflammation pathways. Female participants and those with shorter disease duration may derive greater benefits.