A chemical chaperone-based drug candidate is effective in a mouse model of amyotrophic lateral sclerosis (ALS)

Tamar Getter, Ilana Zaks, Yael Barhum, Tali Ben-Zur, Sebastian Böselt, Simpson Gregoire, Olga Viskind, Tom Shani, Hugo Gottlieb, Omer Green, Moran Shubely, Hanoch Senderowitz, Adrian Israelson, Inchan Kwon, Susanne Petri, Daniel Offen, Arie Gruzman

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the selective death of motor neurons and skeletal muscle atrophy. The majority of ALS cases are acquired spontaneously, with inherited disease accounting for only 10 % of all cases. Recent studies provide compelling evidence that aggregates of misfolded proteins underlie both types of ALS. Small molecules such as artificial chaperones can prevent or even reverse the aggregation of proteins associated with various human diseases. However, their very high active concentration (micromolar range) severely limits their utility as drugs. We synthesized several ester and amide derivatives of chemical chaperones. The lead compound 14, 3-((5-((4,6-dimethylpyridin-2-yl)methoxy)-5-oxopentanoyl)oxy)-N,N-dimethylpropan-1-amine oxide shows, in the micromolar concentration range, both neuronal and astrocyte protective effects in vitro; at daily doses of 10 mg kg-1 14 improved the neurological functions and delayed body weight loss in ALS mice. Members of this new chemical chaperone derivative class are strong candidates for the development of new drugs for ALS patients.

Original languageEnglish
Pages (from-to)850-861
Number of pages12
Issue number5
StatePublished - 1 May 2015


  • amyotrophic lateral sclerosis
  • chemical chaperones
  • drug development
  • in vivo studies
  • superoxide dismutase 1

ASJC Scopus subject areas

  • Drug Discovery
  • General Pharmacology, Toxicology and Pharmaceutics
  • Molecular Medicine
  • Biochemistry
  • Pharmacology
  • Organic Chemistry


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