Abstract
Since mitochondria are energy-generating micro-organisms, most of the disorders in patients with mitochondrial diseases (mt-disease) are considered secondary to defects in ATP synthesis, although some other factors such as reactive oxygen species may be involved. A simultaneous oral administration of febuxostat and inosine was reported to elevate both hypoxanthine and ATP levels in peripheral blood. Based on those results, we attempted co-administration of febuxostat and inosine in two patients with mitochondrial disease: one patient with mitochondrial cardiomyopathy and the other patient with mitochondrial diabetes. In the former case, brain natriuretic peptide (BNP), which is a specific marker for heart failure, was decreased by 31%, and in the latter case, the insulinogenic index increased 3.1 times, suggesting the favorable action of the treatment. Considering that there is no effective treatment available for this disorder, the present therapy may be quite useful for the management of patients with mitochondrial diseases.
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References
Chinnery PF. Mitochondrial disease in adults: what’s old and what’s new? EMBO Mol Med. 2015;7:1503–12.
Alston CL, Rocha MC, Lax NZ, Turnbull DM, Taylor RW. The genetics and pathology of mitochondrial disease. J Pathol. 2017;241:236–50.
Kamatani N, Hashimoto M, Sakurai K, Gokita K, Yoshihara J, Sekine M, et al. Clinical studies on changes in purine compounds in blood and urine by the simultaneous administration of febuxostat and inosine, or by single administration of each. Gout Nucl Acid Metab. 2017;41:171–81.
Garrett RH, Grisham CM. Biochemistry. 6th ed. Philadelphia: Saunders; 2016. p. 927–56.
Kamatani N, Furihata K, Taniguchi A, Fukuuchi T, Yamaoka N, Kaneko K, et al. In vitro enhancement of ATP in human erythrocytes from a healthy subject and two patients with thalassemia and hemoglobinopathy. Gout Nucl Acid Metab. 2018;42:59–64.
Smith AC, Robinson AJ. MitoMiner v3.1, an update on the mitochondrial proteomics database. Nucleic Acids Res. 2016;44:D1258–61.
Harrow J, Frankish A, Gonzalez JM, Tapanari E, Diekhans M, Kokocinski F, et al. GENCODE: the reference human genome annotation for The ENCODE Project. Genome Res. 2012;22:1760–74.
Yao J, Irwin RW, Zhao L, Nilsen J, Hamilton RT, Brinton RD. Mitochondrial bioenergetic deficit precedes Alzheimer’s pathology in female mouse model of Alzheimer’s disease. Proc Natl Acad Sci USA. 2009;106:14670–5.
Swerdlow RH, Burns JM, Khan SM. The Alzheimer’s disease mitochondrial cascade hypothesis: progress and perspectives. Biochim Biophys Acta. 2014;1842:1219–31.
Desler C, Lillenes MS, Tønjum T, Rasmussen LJ. The role of mitochondrial dysfunction in the progression of Alzheimer’s disease. Curr Med Chem. 2017 https://doi.org/10.2174/0929867324666170616110111.
Swerdlow RH, Parks JK, Miller SW, Tuttle JB, Trimmer PA, et al. Origin and functional consequences of the complex I defect in Parkinson’s disease. Ann Neurol. 1996;40:663–71.
Short KR, Bigelow ML, Kahl J, Singh R, Coenen-Schimke J, Raghavakaimal S, et al. Decline in skeletal muscle mitochondrial function with aging in humans. Proc Natl Acad Sci USA. 2005;102:5618–23.
Sun N, Youle RJ, Finkel T. The Mitochondrial basis of aging. Mol Cell. 2016;61:654–66.
Koch J, Mayr JA, Alhaddad B, Rauscher C, Bierau J, Kovacs-Nagy R, et al. CAD mutations and uridine-responsive epileptic encephalopathy. Brain. 2017;140:279–86.
Acknowledgements
The authors appreciate Dr T.A. Johnson for editing the manuscript. The present study was funded by StaGen Co. Ltd.
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NK is employed by and owns stock of StaGen Co. Ltd. The remaining authors declare that they have no conflict of interest.
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Kamatani, N., Kushiyama, A., Toyo-oka, L. et al. Treatment of two mitochondrial disease patients with a combination of febuxostat and inosine that enhances cellular ATP. J Hum Genet 64, 351–353 (2019). https://doi.org/10.1038/s10038-018-0558-0
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DOI: https://doi.org/10.1038/s10038-018-0558-0
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