Injectable borax-loaded alginate hydrogels reduce muscle atrophy, modulate inflammation, and promote neuroprotection in the SOD1G93A mouse model of ALS through mechanisms involving IGF–Akt–mTOR signaling

• Published in: International journal of biological macromolecules Vol. 319; p. 145645
• Main Authors: Rodriguez-Romano, Ana, Gonzalez-Valdivieso, Juan, Moreno-Martinez, Laura, Vázquez Costa, Juan Francisco, Osta, Rosario, Rico, Patricia
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.08.2025
• Subjects: Alginate hydrogel; ALS; Borax; Muscle regeneration; NaBC1 transporter (SLC4A11); ALS; Borax; Muscle regeneration; NaBC1 transporter (SLC4A11); Alginate hydrogel
• ISSN: 0141-8130; 1879-0003; 1879-0003
• DOI: 10.1016/j.ijbiomac.2025.145645

Amyotrophic Lateral Sclerosis (ALS) is a prevalent condition characterized by motor neuron loss and skeletal muscle paralysis. Despite being associated to mutations in over 40 genes, its etiology remains elusive without a cure or effective treatment. ALS, historically considered a motor neuron disease, is defined today as a multisystem disorder involving non-neuronal cell types, including early muscle pathology independent of motor neuron degeneration (dying back hypothesis), thus skeletal muscle actively contributes to disease pathology, making it a viable therapeutic target for ALS. Our previous research has shown that boron transporter NaBC1 (encoded by the SLC4A11 gene), after activation co-localizes with integrins and growth factor receptors synergistically enhancing muscle repair. Here we investigate the effects of injectable alginate-based hydrogels for controlled local borax release in Amyotrophic Lateral Sclerosis muscle. Treated mice showed improved motor function, prolonged survival, and activation of essential muscle metabolic pathways, leading to enhanced muscle repair and reduced atrophy and inflammation. Interestingly, local muscle repair activation provided retrograde neuroprotection by preserving motor neurons and reducing neuro-inflammation. This study highlights the role of muscle tissue in ALS pathology, supporting its targeting with NaBC1-based therapies for muscle regeneration. [Display omitted] •Borax release from injectable alginate hydrogels enhance muscle repair in ALS mice•NaBC1 activation reduces muscle atrophy: less slow fibers, lower FN and SOD1 expression•Borax improves motor function, prolongs survival, and activates muscle metabolism•Controlled borax release preserves motoneurons loss and motoneurons survival and reduces neuroinflammation•This work highlights the involvement of skeletal muscle in ALS as a primary target