Olesoxime in Neurodegenerative Diseases: Scrutinising a Promising Drug Candidate.

Olesoxime in Neurodegenerative Diseases: Scrutinising a Promising Drug Candidate.

Publication date: Jul 05, 2019

Over the last years, the experimental compound olesoxime, a mitochondria-targeting cholesterol derivative, has emerged as a promising drug candidate for neurodegenerative diseases. Numerous preclinical studies have successfully proved olesoxime’s neuroprotective properties in cell and animal models of clinical conditions such as amyotrophic lateral sclerosis, Huntington disease, Parkinson disease, peripheral neuropathy and spinal muscular atrophy. The beneficial effects were attributed to olesoxime’s potential impact on oxidative stress, mitochondrial permeability transition or cholesterol homoeostasis. Although no significant benefits have been demonstrated in patients of amyotrophic lateral sclerosis, and only the first 12 months of a phase II/III clinical trial showed an improvement in motor symptoms of spinal muscular atrophy, this orphan drug may still offer undiscovered potential in the treatment of neurological diseases. In our earlier preclinical studies, we demonstrated that administration of olesoxime in mouse and rat models of Huntington disease improved psychiatric and molecular phenotypes. Aside from stabilising mitochondrial function, the drug reduced the overactivation of calpains, a class of calcium-dependent proteases entangled in neurodegenerative conditions. This observation may be credited to olesoxime’s action on calcium dyshomeostasis, a further hallmark in neurodegeneration, and linked to its targets TSPO and VDAC, two proteins of the outer mitochondrial membrane associated with mitochondrial calcium handling. Further research into the mode of action of olesoxime under pathological conditions, including its effect on neuronal calcium homeostasis, may strengthen the untapped potential of olesoxime or other similar compounds as a therapeutic for neurodegenerative diseases.

Weber, J.J., Clemensson, L.E., Schi”oth, H.B., and Nguyen, H.P. Olesoxime in Neurodegenerative Diseases: Scrutinising a Promising Drug Candidate. 06567. 2019 Biochem Pharmacol.

Concepts Keywords
Amyotrophic Lateral Sclerosis Mitochondria associated membranes
Calcium Neuroprotection
Calpains Olesoxime
Cholesterol Translocator protein
Clinical Trial Neurodegeneration
Derivative Degenerative disease
Homeostasis Mitochondria
Huntington Organ systems
Mitochondria Nervous system
Mitochondrial Senescence
Neurodegeneration Branches of biology
Neurodegenerative Spinal muscular atrophy
Neurodegenerative Diseases
Neurological Diseases
Orphan Drug
Outer Mitochondrial Membrane
Oxidative Stress
Parkinson Disease
Peripheral Neuropathy
Phase II
Spinal Muscular Atrophy


Type Source Name
drug DRUGBANK Calcium
pathway BSID Oxidative Stress
disease MESH oxidative stress
disease MESH spinal muscular atrophy
disease DOID spinal muscular atrophy
disease DOID peripheral neuropathy
disease DOID peripheral neuropathy
disease MESH peripheral neuropathy
disease DOID Parkinson disease
disease MESH Parkinson disease
disease DOID Huntington disease
disease MESH Huntington disease
disease DOID amyotrophic lateral sclerosis
disease MESH amyotrophic lateral sclerosis
drug DRUGBANK Cholesterol
disease MESH Neurodegenerative Diseases
pathway BSID Neurodegenerative Diseases

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