Because of increasing evidence of metabolic disturbances in amyotrophic lateral sclerosis patients, researchers at the University of Queensland tested whether ALS could be targeted at the metabolic level. Results indicate that by increasing energy sources with the triglyceride supplement triheptanoin, they could delay motor neuron loss in an animal model.
The study, titled “Triheptanoin Protects Motor Neurons and Delays the Onset of Motor Symptoms in a Mouse Model of Amyotrophic Lateral Sclerosis,” was published in the journal PlosOne.
In ALS patients, cells are unable to produce normal levels of energy due to defects in mitochondria, the main cellular production site of the energy-carrying molecule ATP. Both patients and animal models of ALS have shown abnormalities in the pathways leading to ATP production such as glucose uptake, glycolysis, TCA, and the electron transport chain.
Triheptanoin is a synthetic fat which is broken down in the liver into substances that can be used to generate energy. It is already being used as a dietary supplement by individuals enrolled in medical research studies about metabolic disorders.
In the current study, researchers gave either control or triheptanoin-containing diet treatments to pre-symptomatic animals in the same dose used to treat patients with metabolic disorders. They found that treated mice showed 33 percent less motor neuron loss in the spinal cord. The scientists suggest that triheptanoin’s neuroprotective effect is due to increased mitochondrial function and improved energy supply.
Additionally, triheptanoin improved motor symptoms such as grip strength and body balance. It also delayed loss of body weight. The effects could be due in part to increased expression of enzymes involved in muscle metabolism.
The study revealed that triheptanoin is a promising new treatment approach for ALS in order to delay motor neuron loss and the onset of motor symptoms. Still, the authors are aware that they will have to increase animal numbers and initiate treatment in symptomatic stages, which would be the case in ALS patients.
“Thus, while triheptanoin was given at a presymptomatic stage of disease in mice, it is difficult to correlate our findings to the clinical course of disease in patients. Given the difficulty in diagnosing ALS, future studies are required to evaluate the extent to which triheptanoin can preserve motor neurons and motor function when treatment is initiated in ALS models with obvious muscle and/or neuronal impairments,” the authors explained in the study report.