The authors of this article are researching Huntington’s disease and the biomarkers that indicate the presence of this disease. The main method that they use was metabolomics. This helped the researchers understand both the metabolic and physiological phenomena that occur in patients with Huntington’s disease. Understanding these things could lead to early diagnosis and eventually a cure for this disease.

            Huntington’s disease is neurogenerative disease that results from the extension of the cytosine-adenine-guanine sequence in the Huntingtin gene. The magnitude of the extension is inverse to the age that the disease will be seen in. In other words, the more severe the extension of the cytosine-adenine-guanine sequence, the earlier the disease will present itself.

            Researchers in this study obtained fourteen samples of brain tissue from deceased Huntington’s disease patients and fourteen samples from diseased patients with no known Huntington’s disease. The only major difference between all of these patients was age. All other factors were relatively similar. The brain samples were then vacuum dried, freezer dried, and ground into a powder using liquid nitrogen. The metabolites were separated and collected to be studied. 

            The results of this study showed the difference in metabolites between the control group and the fourteen patients with Huntington’s disease. Researchers found that on average, fifty-five metabolites differed in the frontal lobe between patients with Huntington’s disease and patients who did not have the disease. Additionally, about twenty-six metabolites differed in the striatum. The researchers predict that the lower number of differences in the striatum is due to the extensive neuronal loss in the striatum. The researchers determined that the main biochemical pathway that was responsible for the differences in metabolites was the beta-oxidation of very long fatty acid chains and the oxidation of branched chain fatty acids. 

            The main types of metabolites that were affected in patients with the disease were acylcarnitine and phospholipid metabolites. These two types of metabolites have very different but significant functions. Acylcarnitine metabolites are used to transport fatty acids into the mitochondria. This plays a role in energy production and the stabilization of the cell which is vital to life. The levels of acylcarnitine metabolites are much lower in patients with Huntington’s disease, which leads to a decrease in the ability to process and use energy. On the other hand, an abundance of phospholipid metabolites is found in patients with Huntington’s disease. These metabolites are believed to act as biomarkers for apoptosis. The elevated levels of phospholipid metabolites leads to healthy cells undergoing unnecessary apoptosis. These abnormal levels are detrimental to normal metabolic process in the brain. 

The researchers in this study argue that their methods are superior to other studies because they studied two separate areas of the brain, and their study is easily reproducible due to the availability of the technology they utilized. This study used many different tests to prove their predictions, including high-resolution mass spectrometry, proton nuclear magnetic resonance, and direct injection liquid chromatography mass spectrometry. All of these factors increase the credibility of this study.

In conclusion, this study proved that using deceased patient’s brain tissue can lead to many breakthroughs in understanding Huntington’s disease. The understanding of the disease will hopefully lead to early diagnosis and eventually a cure. 

Works Cited

Graham, S. F. et al. Targeted biochemical profiling of brain from Huntington’s disease patients reveals novel metabolic pathways of interest. BBA Molecular Basis of Disease 1864, 2430-2437 (2018).