​Metabolic Therapy with Deanna Protocol Supplementation Delay Disease Progression and Extends Survival in Amyotrophic Lateral Sclerosis (ALS) Mouse Model

Metabolic Therapy with Deanna Protocol Supplementation Delay Disease Progression and Extends Survival in Amyotrophic Lateral Sclerosis (ALS) Mouse Model

Amyotrophic Lateral Sclerosis (ALS), has become the most common adult onset motor neuron disease, symptoms can vary from spasticity, hyperreflexia, weakness, paralysis and impaired respiratory function. Though varying types of ALS can occur, all patients exhibit neuronal cell death, which may be caused by excess glutamate and oxidative stress-induced metabolic dysfunction. Which can be demonstrated by mitochondrial dysregulation, oxidative stress, glutamate excitotoxicity, and motor neuron death. These factors are a result of impaired energy metabolism and previous research has exhibited the ketogenic diet can deter the impairment of motor function and reduces death of motor neurons in the spinal cord of mice.

In addition, patients have also demonstrated symptomatic improvement in motor control following implementation of Deanna Protocol (DP). This consists of mainly arginine alpha-ketoglutarate and other agents that have been reported to maintain metabolic function and prevent glutamate excitotoxicity. In hopes to reverse or slow disease progression through supporting mitochondrial function and supplying alternative energy for neurons and glial cell, the researchers sought out to administer anaplerotic substrates and cofactors or the DP alone or with a KD.

Forty-eight male transgenic mice were divided into four groups, supplied a standard diet (n=13), using standard diet and DP (n=12), KD alone (n=11), and KD with DP (n=12). Motor function was assessed weekly with the accelerating rotarod test, grip test and hanging wire test. Also measured were, ability to return to normal, upright position, paralysis of hind limbs, body weight, blood glucose and BHB.

Blood parameters showed blood BHB was 53% higher in KD and 52% higher in KD+DP, along with greater brown adipose tissue was 30%, 38% and 46% greater in KD, KD+DP, and SD+DP. The accelerating rotarod data exhibited a significantly better motor function in KD mice, compared to SD. KD also showed elevated motor performance and significantly better in the SD+DP group, showing similar results in the PaGEtest as well. The SD+DP group demonstrated significantly improved neurological scores compared to all other diet groups, which indicated delayed progression of the disease. Mean survival only showed significant differences in the KD+DP and SD+DP groups, 63.3% and 72.7% of animals survived past 125 days respectively.

Demonstrating the DP supplementation added to a standard or ketogenic diet may improve motor function, delay neurological effects, and even extend survival in mice. The researchers discussed the most significant result was the improved motor function n the SD+DP group, when compared to control animals. Further research on the benefits of ketogenicdieting and the utilization of ketones as an energy source is required, to assist in the inhibition of disease progression and detriments in degenerative disease such as ALS.