PMID- 20721828
OWN - NLM
STAT- MEDLINE
DCOM- 20101213
LR  - 20211020
IS  - 2040-3410 (Electronic)
IS  - 1369-7056 (Print)
IS  - 1369-7056 (Linking)
VI  - 13
IP  - 8
DP  - 2010 Aug
TI  - Olesoxime, a cholesterol-like neuroprotectant for the potential treatment of 
      amyotrophic lateral sclerosis.
PG  - 568-80
AB  - Effective therapies are needed for amyotrophic lateral sclerosis (ALS), a 
      debilitating and fatal motor neuron disease. Cell and animal models of ALS are 
      beginning to reveal possible principles governing the biology of motor 
      neuron-selective vulnerability that implicate mitochondria and the mitochondrial 
      permeability pore (mPTP). Proteins associated with the mPTP are known to be 
      enriched in motor neurons and the genetic deletion of a major regulator of the 
      mPTP has robust effects in ALS transgenic mice, delaying disease onset and 
      extending survival. Thus, the mPTP is a rational, mechanism-based target for the 
      development of drugs designed to treat ALS. Trophos SA has discovered olesoxime 
      (TRO-19622), a small-molecule with a cholesterol-like structure, which has 
      remarkable neuroprotective properties for motor neurons in cell culture and in 
      rodents. Olesoxime appears to act on mitochondria, possibly at the mPTP. Phase I 
      clinical trials of olesoxime have been completed successfully. Olesoxime is well 
      tolerated and achieves levels predicted to be clinically effective when 
      administered orally. It has been granted orphan drug status for the treatment of 
      ALS in the US and for the treatment of spinal muscular atrophy in the EU. Phase 
      II/III clinical trials are in progress in Europe.
FAU - Martin, Lee J
AU  - Martin LJ
AD  - Johns Hopkins University School of Medicine, Departments of Pathology and 
      Neuroscience, Baltimore, MD 21205-2196, USA. martinl@jhmi.edu
LA  - eng
GR  - R01 NS065895-01/NS/NINDS NIH HHS/United States
GR  - R01 NS052098/NS/NINDS NIH HHS/United States
GR  - NS052098/NS/NINDS NIH HHS/United States
GR  - R01 AG016282-01A1/AG/NIA NIH HHS/United States
GR  - R01 NS052098-02/NS/NINDS NIH HHS/United States
GR  - AG016282/AG/NIA NIH HHS/United States
GR  - R01 NS065895/NS/NINDS NIH HHS/United States
GR  - R01 AG016282/AG/NIA NIH HHS/United States
GR  - NS065895/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, P.H.S.
PT  - Review
PL  - England
TA  - IDrugs
JT  - IDrugs : the investigational drugs journal
JID - 100883655
RN  - 0 (Cholestenones)
RN  - 0 (Mitochondrial Membrane Transport Proteins)
RN  - 0 (Mitochondrial Permeability Transition Pore)
RN  - 0 (Neuroprotective Agents)
RN  - A6778U5IFY (olesoxime)
SB  - IM
MH  - Amyotrophic Lateral Sclerosis/*drug therapy/metabolism
MH  - Animals
MH  - Cholestenones/adverse effects/pharmacology/*therapeutic use
MH  - Humans
MH  - Mitochondrial Membrane Transport Proteins/metabolism
MH  - Mitochondrial Permeability Transition Pore
MH  - Neuroprotective Agents/adverse effects/pharmacology/*therapeutic use
PMC - PMC3058503
MID - NIHMS276664
EDAT- 2010/08/20 06:00
MHDA- 2010/12/14 06:00
PMCR- 2011/03/16
CRDT- 2010/08/20 06:00
PHST- 2010/08/20 06:00 [entrez]
PHST- 2010/08/20 06:00 [pubmed]
PHST- 2010/12/14 06:00 [medline]
PHST- 2011/03/16 00:00 [pmc-release]
PST - ppublish
SO  - IDrugs. 2010 Aug;13(8):568-80.