Huntington’s disease

7 Jun 2017


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.

Medesis Pharma’s proposed treatment is based on using RNA interference to block the expression of the mutant Huntingtin (Htt) responsible for neuronal death.

The drug delivery technology developed by Medesis Pharma enables the oral administration of non-modified siRNAs by carrying them in HDL lipoproteins which are structured at the crossing of the oral mucosa and delivering them intact into all cells, particularly neurons and astrocytes, crossing the blood-brain barrier.

The strategy involves sequencing the patient’s two alleles in order to determine which sequence the patient has on the mutated allele and the wild-type allele (depending on the patients, for each SNP, the specific siRNA for their mutant allele would therefore need to be used, while the other siRNA may need to be used for another patient’s mutant allele).

A European Medicines Agency (EMA) consultation is being prepared to approve the product’s clinical development.