Koopman 2016 EMBO Mol Med
| Koopman WJ, Beyrath J, Fung CW, Koene S, Rodenburg RJ, Willems PH, Smeitink JA (2016) Mitochondrial disorders in children: toward development of small-molecule treatment strategies. EMBO Mol Med 8:311-27. |
Koopman WJ, Beyrath J, Fung CW, Koene S, Rodenburg RJ, Willems PH, Smeitink JA (2016) EMBO Mol Med
Abstract: This review presents our current understanding of the pathophysiology and potential treatment strategies with respect to mitochondrial disease in children. We focus on pathologies due to mutations in nuclear DNA-encoded structural and assembly factors of the mitochondrial oxidative phosphorylation (OXPHOS) system, with a particular emphasis on isolated mitochondrial complex I deficiency. Following a brief introduction into mitochondrial disease and OXPHOS function, an overview is provided of the diagnostic process in children with mitochondrial disorders. This includes the impact of whole-exome sequencing and relevance of cellular complementation studies. Next, we briefly present how OXPHOS mutations can affect cellular parameters, primarily based on studies in patient-derived fibroblasts, and how this information can be used for the rational design of small-molecule treatment strategies. Finally, we discuss clinical trial design and provide an overview of small molecules that are currently being developed for treatment of mitochondrial disease.
© 2016 The Authors. Published under the terms of the CC BY 4.0 license. • Keywords: Children, Clinical trial, Drug development, Mitochondria, Outcome measures
• O2k-Network Lab: NL Nijmegen Koopman WJ, NL Nijmegen Rodenburg R
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Stress:Mitochondrial disease
