The preclinical study results were presented at the European Society of Gene and Cell Therapy (ESGCT) 25th Anniversary Congress, held Oct. 17-20 in Berlin, Germany. The study was conducted in collaboration with Charles River Discovery Research Services in Finland.
Huntington’s, a fatal genetic neurodegenerative disease, leads to changes in motor coordination, coginitive decline, depression, involuntary muscle movements, diminished speech and difficulty swallowing. The disease worsens over time, causing complete physical and mental deterioration.
Huntington’s disease is caused by an autosomal dominant mutation (passed down from a nonsex chromosome from one parent) in the huntingtin gene, leading to a mutated protein that is prone to aggregation. HD remains without effective treatments for delay of onset or to slow the progression of a patient’s decline.
AMT-130 comprises a recombinant noninfectious viral vector carrying DNA that encodes a micro RNA that silences the human huntingtin and, therefore, the production of the mutated protein.
The study builds on data previously generated at uniQure, which revealed that a single administration of AMT-130 led to a long-term suppression of mutant huntingtin protein in a mouse model of HD.
The current study was conducted in a different mouse model, characterized by rapid disease progression, early onset of motor symptoms, and a significantly reduced lifespan.
Results from the new HD mouse model demonstrated that a single administration of AMT-130 into the striatum brain region resulted in a significant improvement of motor coordination and median survival, from 120 to 149 days, compared to controls.
Scientists also observed a dose-dependent decrease in the levels of mutant huntingtin.
“We are confident that the combination of suppression of neuronal dysfunction, improvement of HD symptoms, extended survival and long-term huntingtin lowering observed in these studies, could translate into patient benefit and improve their quality of life,” Sander van Deventer, MD and PhD, the chief scientific officer at uniQure, said in a press release.
“We have now begun our investigational new drug-enabling toxicology studies in rodents and non-human primates that will support an IND application for AMT-130 next year,” van Deventer said.
Submitting an investigational new drug (IND) application to the U.S. Food and Drug Administration is an important step toward human clinical studies of a new therapy.