HUNTINGTON’S DISEASE, HD

Huntington’s Disease (HD) is a fatal autosomal dominant progressive neurodegenerative disease, characterized by progressive motor impairment (involuntary movements, chorea, dyskinesia, dystonia), psychiatric disturbances (change in mood, depression, etc.) and cognitive decline (memory loss, slowed thinking, speech disturbance, overall decline in executive functions). In Caucasian populations of Western Europe, North America and Australia, the prevalence of the disease is 5.7/100 000. HD is associated with a CAG repeat expansion in the 5’ region of the first exon of the Huntingtin (HTT) gene.

Mutated HTT and N-terminal fragments accumulate in both the cytoplasm and the nucleus of neural cells and are at the origin of a number of intracellular perturbations/deficiencies that lead to disease progression.

Currently, there is no efficient treatment for this disease.

 

NP03 Clinical Development in HD

Preclinical studies on the disease-modifying effect of NP03 on HD have been conducted on the YAC128 transgenic mouse model in collaboration with the laboratory of Pr. Michael Hayden (University of British Columbia, Vancouver CA), internationally recognised in the HD research field, and founder of this model (see Pouladi et al. 2012).

  • NP03 significantly improved motor performance
  • NP03 had no adverse effect on body weight and no obvious toxic side effects associated with long-term (10-month) treatment
  • NP03 prevented the loss of striatal volume and restored striatal neuronal counts in YAC128 mice
  • NP03 significantly improved the level of the striatal marker DARPP-32, and the testicular atrophy observed in YAC128 HD mice
  • NP03 significantly reduced the levels of soluble mHTT in both plasma and striatal tissues, the levels of aggregated mHTT in the striatum.
  • NP03 significantly induced BDNF expression in blood
  • NP03 inhibited GSK-3, and reduced phosphorylation of its substrate tau protein.

See full text paper here.

A phase I has been completed and a phase II clinical study is planned for the treatment of depression and mood disorders associated with HD.

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