Olesoxime (TRO19622) is an experimental drug formerly under development by the now-defunct French company

Trophos Trophos was a biopharmaceutical company specialising in the discovery and development of novel therapeutics to treat both orphan neurodegenerative diseases and more prevalent disorders. Trophos was founded in 1999 in Marseille by three scientist ...

as a treatment for a range of

neuromuscular disorders A neuromuscular disease is any disease affecting the peripheral nervous system (PNS), the neuromuscular junction, or skeletal muscle, all of which are components of the motor unit. Damage to any of these structures can cause muscle atrophy and ...

. It has a

cholesterol Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell mem ...

-like structure and belongs to the

- oxime family of mitochondrial pore modulators.

Research

In preclinical studies, the compound displayed neuroprotective properties by promoting the function and survival of neurons and other cell types under disease-relevant stress conditions. It did so through interactions with two components of the

mitochondrial permeability transition pore The mitochondrial permeability transition pore (mPTP or MPTP; also referred to as PTP, mTP or MTP) is a protein that is formed in the inner membrane of the mitochondria under certain pathological conditions such as traumatic brain injury and stroke ...

(mPTP), VDAC and TSPO. In preclinical studies on

Huntington's disease Huntington's disease (HD), also known as Huntington's chorea, is a neurodegenerative disease that is mostly inherited. The earliest symptoms are often subtle problems with mood or mental abilities. A general lack of coordination and an unst ...

, the disease-attenuating effects of olesoxime were attributed to modulating the activity of calcium-dependent proteases called calpains. A 2009–2011 phase 3

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietar ...

amyotrophic lateral sclerosis Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or Lou Gehrig's disease, is a neurodegenerative disease that results in the progressive loss of motor neurons that control voluntary muscles. ALS is the most comm ...

did not demonstrate an increase in survival. A 2011–2013 trial in

spinal muscular atrophy Spinal muscular atrophy (SMA) is a rare neuromuscular disorder that results in the loss of motor neurons and progressive muscle wasting. It is usually diagnosed in infancy or early childhood and if left untreated it is the most common genetic ...

(SMA) indicated that the compound may prevent deterioration of muscle function. In 2015, the entire olesoxime programme was purchased by

Hoffmann-La Roche F. Hoffmann-La Roche AG, commonly known as Roche, is a Swiss multinational healthcare company that operates worldwide under two divisions: Pharmaceuticals and Diagnostics. Its holding company, Roche Holding AG, has shares listed on the SIX ...

for €120 million with a view to developing a treatment for SMA. However, in June 2018, faced with technical and regulatory challenges and competition from a potentially more effective drug nusinersen, Roche halted further development of olesoxime.

References

External links

* {{MeSH name, cholest-4-en-3-one,%20oxime, 3=cholest-4-en-3-one, oxime' Drugs with unknown mechanisms of action Cholestanes Ketoximes Hoffmann-La Roche brands Spinal muscular atrophy

Research

References

Further reading

External links