Rare Disease Report

Gene Therapy for Huntington's Disease in Development

AUGUST 14, 2017
James Radke
Uniqure, the company best known for having the first approved gene therapy put on the market (for familial chylomicronemia syndrome), is expanding its pipeline to include a gene therapy for Huntington’s disease.
While still in early development, the company stated they plan to file an Investigational New Drug (IND) application next year with the US Food and Drug Administration (FDA) in order to begin clinical studies in humans.
Huntington's disease is a genetic neurodegenerative disorder that leads to loss of muscle coordination, behavioral abnormalities and cognitive decline when a person enters their 3rd or 4th decade. The disease is an autosomal dominant mutation, meaning that if a person has the condition, there is a 50% chance their offspring will have it as well, and is due to a mutation on the huntingin gene.
Despite good understanding of the condition, current treatments can only alleviate the symptoms of it, but they do not delay the onset or slow the progression of the disease. It is hopeful that gene therapy can do that.
In Huntington’s disease animal models, the gene therapy called AMT-130, an AAV5 vector carrying a DNA cassette encoding artificial micro-RNA, is effective. In April, data was presented at the 12th Annual CHDI HD Therapeutics Conference in Malta showing the drug was able to silence the human mutant huntingtin gene in pig model.
In the animal study, AMT-130 was administered into the striatum and thalamus of minipigs that had the mutant Huntingtin gene. Three months after treatment, the vector was observed throughout the minipig brain and expression of mutant HTT mRNA was significantly reduced in the striatum and thalamus by 50% to 80% and reductions were also observed in the cortex (reduced up to 40% compared to controls).
Lead author of that study, Prof. Jan Motlik, Director of the Institute of Animal Physiology and Genetics in the Czech Republic said, "This study demonstrated that a single administration of AAV5-miHTT resulted in significant reductions in HTT mRNA in all regions of the brain transduced by AMT-130, as well as in the cortex. Consistent with the reduction in HTT mRNA, we also observed a clear dose-dependent reduction in mutant huntingtin protein levels in the brain, with similar trends in the cerebral spinal fluid. Taking into account the similarities of CHDI's proprietary transgenic pig model to the human brain, these results provide additional data to support moving forward with clinical trials of uniQure's promising gene therapy for Huntington's disease."
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