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Use of chlorine guanabenz derivatives for treating polyglutamines expansion associated diseases



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Priority patent application EP06291547 filed on October 4th, 2006 entitled “Use of chlorine Guanabenz derivatives for treating polyglutamine expansion associated diseases”



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Régulation de l’expression génétique, UMR8541, Paris, France?



The prevalence of Huntington’s disease (HD) is estimated to 3-7 per 100,000 people in western Europe. HD is caused by a faulty gene on chromosome 4. This gene produces a protein called Huntingtin and leads to a damage of the striatal neurons. The progressive degeneration of these neurons causes gradual physical, mental and emotional changes. At this time, there is no way to stop or to reverse the course of HD. HD is characterized by expansion of CAG codons translated in polyglutamine (polyQ) and causes aggregation of the affected protein. The aim of the invention concerns non toxic compounds capable of treating polyglutamine expansion associated diseases.


The present invention relates to chlorine Guanabenz derivatives (inhibitors of aggregated proteins) for treating Huntington’s disease and other polyglutamine expansion associated diseases. More specifically, it relates to the use of the molecule of formula (I) wherein R=H or Cl and the phenyl group is at least substituted twice, or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament for treating polyglutamine expansion associated diseases. Guanabenz and Chloroguanabenz specifically reduce accumulation of a pathogenic fragment of Huntingtin in a transiently transfected cellular model of HD.

Formula I


Guanabenz is a drug already in clinic to treat hypertension. This invention makes it possible to develop a new application of the chlorine Guanabenz derivatives.

Guanabenz is a novel drug candidate for Huntington’s disease treatment.


The Guanabenz derivatives described in this invention promote clearance of mutant Huntingtin and this opens new applications in preventing or treating pathological of polyglutamine expansion associated diseases such as HD. Furthermore this invention will be more generally applicable to all protein misfolding diseases. The commercial applications and potential markets in such therapeutics are huge.


Information about the molecular mechanism by which Guanabenz enhances clearance of misfolded proteins is a prerequisite for clinical development. The inventors are exploring the pathway by which the Guanabenz increases the cellular capacity to degrade aggregation-prone proteins.

For further information, please contact us (Ref 86877-07)

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