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Novel Therapies Targeting Inner Mitochondrial Membrane—From Discovery to Clinical Development

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ABSTRACT

Mitochondrial oxidative stress and dysfunction have been implicated in the aging process and in numerous chronic diseases. The need for therapies that can protect and/or improve mitochondrial function is obvious. However, the development of mitoprotective drugs has been hampered by a number of challenges, and there are at present no approved therapies for mitochondrial dysfunction. This article describes the original discovery, preclinical development, and clinical development of a novel class of small peptide molecules that selectively target the inner mitochondrial membrane and protect mitochondrial function. These compounds have the potential to be a paradigm-shifting approach to the treatment of mitochondrial dysfunction, which underlies many common diseases, including cardiorenal, neurologic, and metabolic disorders.

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Abbreviations

ATP:

adenosine triphosphate

BBB:

blood-brain barrier

CypD:

cyclophilin D

Cyt c:

cytochrome c

ETC:

electron transport chain

IMM:

inner mitochondrial membrane

iv :

intravenous

MCAT:

overexpression of catalase targeted to mitochondria

MPP+ :

1-methyl-4-phenylpyridium

MPT:

mitochondrial permeability transition

MPTP:

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

OMM:

outer mitochondrial membrane

ROS:

reactive oxygen species

sc :

subcutaneous

SOD:

superoxide dismutase

TPP+ :

triphenylphosphonium ion

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DISCLOSURES

The SS peptides described in this article are licensed for commercial research and development to Stealth Peptides Inc., a clinical stage biopharmaceutical company, in which the authors have financial interests.

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Authors and Affiliations

  1. Department of Pharmacology, Joan and Sanford I. Weill Medical College of Cornell University, 1300 York Avenue, New York, New York, 10021, USA

    Hazel H. Szeto

  2. Laboratory of Chemical Biology and Peptide Research, Clinical Research Institute of Montreal, Montreal, Quebec, Canada

    Peter W. Schiller

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  1. Hazel H. Szeto
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  2. Peter W. Schiller
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Correspondence to Hazel H. Szeto.

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Szeto, H.H., Schiller, P.W. Novel Therapies Targeting Inner Mitochondrial Membrane—From Discovery to Clinical Development. Pharm Res 28, 2669–2679 (2011). https://doi.org/10.1007/s11095-011-0476-8

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  • DOI: https://doi.org/10.1007/s11095-011-0476-8

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