Methodological and Analytical Limitations Undermine Reported Outcomes of Spinal DC Stimulation in ALS

Amyotrophic lateral sclerosis (ALS) is a fatal motoneuron disease that causes progressive loss of motor function and paralysis. While the exact causes of motoneuron degeneration remain unclear, abnormal electrical excitability of motoneurons (1) and altered cortical excitability (2) are consistent features (2). Treatments that normalize this excitability have shown promise in animal studies and influence current approved drugs (3, 4). However, existing pharmacological therapies provide only limited improvements in motor function and survival (5–8), highlighting the need for more effective treatment approaches.

Electroceuticals, which use targeted electrical stimulation rather than systemic drugs, offer a promising approach to regulate neuronal excitability. Therefore, a variety of electrical stimulation approaches have been studied in ALS including cortical (2, 9) and spinal (10–15) stimulations. So far, results are variable and the clinical impacts on disease progression have been limited (16).

Standing out from these prior studies, a recent study by Ahmed et al. examined the effects of anodal spinal DCS on the SOD1-G93A mouse model of ALS using unique electrode placements called “Multi-path DCS” (17). The treatment effects reported were profound, including prolonged motor function and an astounding improvement in animal survival of 74% (17). Such significant results warrant a deeper look into the study, which unfortunately uncovers several flaws that undermine the impact of results, as explained below. All figures referenced in the following text pertain to the Ahmed et al. study (17).