Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder of motor neurons causing progressive muscle weakness, paralysis, and eventual death from respiratory failure. There is currently no cure or effective treatment for ALS. The Deanna protocol (DP) is a comprehensive treatment approach that includes a metabolic therapy in the form of a supplement complex that improved neurological function, increased motor function and survival in SOD1-G93A mice and has been reported to alleviate symptoms in patients with ALS; therefore, it has been proposed as a treatment for the disease.

We hypothesized that the major components of the DP, including arginine alpha-ketoglutarate, gamma amino butyric acid (GABA), medium chain triglycerides (MCT), and soluble coenzyme Q10 (ubiquinol) supports energy metabolism by increasing energy intermediates of the tricarboxylic acid cycle in a mouse model of ALS (SOD1-G93A).

We explored the potential therapeutic use of DP by testing the effects of DP supplementation on the metabolomics profile of SOD1-G93A mice. In addition, we assessed time to paralysis in a Caenorhabditis elegans model of ALS (TDP-43) given DP supplementation. SOD1-G93A mice were fed a standard rodent diet (SD) or SD with low dose (LOW) or high dose of DP (HIGH). Global metabolomics analysis was performed on blood plasma from treated and untreated animals. Additionally, the time to paralysis of TDP-43 ALS C. elegans treated with and without the individual and combination DP supplements was measured.

30 and 49 biochemicals were significantly altered in the plasma of LOW and HIGH groups, respectively. Metabolites associated with mitochondrial energy metabolism, arginine metabolism, as well as long- and medium-chain fatty acids, GABA and related intermediates were elevated in response to DP. Elements of DP, arginine and alpha-ketoglutarate, GABA, and MCTs prolonged the rate of final paralysis of C. elegans TDP-43 disease models.

Targeting energy metabolism with the DP supplement as a metabolic therapy produces a change in the global metabolic profile of ALS mice that support the role of the DP for enhanced mitochondrial energy metabolism and prolongs time to paralysis of ALS C. elegans.