uniQure is a leading gene therapy company advancing transformative therapies for patients with severe medical needs.
Spinocerebellar Ataxia Type 3, also known as Machado-Joseph disease, is caused by a CAG-repeat expansion in the ATXN3 gene that results in an abnormal form of the toxic protein ataxin-3, leading to brain degeneration that results in movement disorders, rigidity, muscular atrophy and paralysis.
The company has engineered an artificial microRNA candidate, AMT-150, to target the ataxin-3 gene in a SCA3 knock-in mouse model.
An inactivated virus vector is used to deliver AMT-150 to the nerve cells. The virus containing AMT-150 is injected close to the cerebellum.
The 6-week proof-of-concept study demonstrated that a single AMT-150 injection in the cerebrospinal fluid resulted in significant mutant ataxin-3 lowering at each of the primary sites of disease neuropathology, namely the cerebellum (up to 53%) and brainstem (up to 65%).
These results were corroborated by preclinical studies in human induced Pluripotent Stem Cell (iPSC)-derived neurons showing a dose-dependent lowering of ataxin-3 mRNA of up to 55%.
These studies further demonstrate the potential utility and safety profile of the miQURE™ technology, the Company’s proprietary gene-silencing platform.
“We believe that the data from these preclinical studies in the knock-in mouse model and in iPSC-derived neurons show the potential of AMT-150 to alter the course of this devastating disease after a single administration,” stated Sander van Deventer, M.D., Ph.D., chief scientific officer at uniQure.
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Press release, 7 May 2019
