Open AccessExploring mTOR inhibition as treatment for mitochondrial disease
Author(s) -
SageSchwaede Abigail,
Engelstad Kristin,
Salazar Rachel,
Curcio Angela,
Khandji Alexander,
Garvin Jr James H.,
De Vivo Darryl C.
Publication year - 2019
Publication title -
annals of clinical and translational neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.824
H-Index - 42
ISSN - 2328-9503
DOI - 10.1002/acn3.50846
Subject(s) - medicine , lactic acidosis , melas syndrome , pi3k/akt/mtor pathway , mitochondrial encephalomyopathy , mitochondrial disease , pathological , disease , discovery and development of mtor inhibitors , bioinformatics , everolimus , mitochondrial dna , mitochondrion , mechanistic target of rapamycin , mitochondrial myopathy , signal transduction , genetics , biology , gene
Leigh syndrome and MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke‐like episodes) are two of the most frequent pediatric mitochondrial diseases. Both cause severe morbidity and neither have effective treatment. Inhibiting the mammalian target of rapamycin (mTOR) pathway has been shown in model mice of Leigh syndrome to extend lifespan and attenuate both the clinical and pathological progression of disease. Based on this observation, we treated two children with everolimus, a rapamycin analogue. The child with Leigh syndrome showed sustained benefit, while the child with MELAS failed to respond and died of progressive disease. We discuss possible mechanisms underlying these disparate responses to mTOR inhibition.