Clovertex’s Target of the Year is mutant huntingtin (mHTT), the toxic form of the huntingtin protein generated by an expanded CAG repeat in the HTT gene, the singular genetic cause of Huntington’s disease. The expanded polyglutamine tract causes the protein to misfold and aggregate in neurons, disrupting transcription, axonal transport, mitochondrial function, and synaptic signaling. This leads to selective degeneration in the striatum and cortex, driving the progressive cognitive, psychiatric, and motor symptoms of the disease. Because Huntington’s is monogenic and driven by a single toxic protein, mHTT has long stood out as a rare “root-cause” target in neurodegeneration: lower the protein, and you may directly slow or even arrest the disease process itself.
This past year, uniQure’s gene therapy AMT‑130 emerged as a real-world test of that hypothesis. The treatment is delivered through MRI-guided neurosurgery, using convection-enhanced infusion of an AAV5 vector directly into the striatum. The striatum is also the site of the earliest and most pronounced neuronal loss in Huntington’s disease, particularly in the medium spiny neurons that make up the bulk of its volume. By targeting the therapy directly to this region, AMT‑130 is designed to act where the damage begins, enabling long-term suppression of huntingtin protein in the most affected cells. In topline Phase I/II results announced in September 2025, patients in the high-dose cohort followed for 36 months showed approximately 75% slowing of disease progression compared to matched controls, as measured by the composite Unified Huntington’s Disease Rating Scale (cUHDRS). Functional measures and biomarkers showed consistent trends, supporting a meaningful biological effect.
Taken together, these results not only reinforce mHTT as a compelling root‑cause target but also provide one of the first human clinical signals suggesting a gene therapy can alter the trajectory of Huntington’s disease, deepening confidence in CNS‑directed silencing strategies even as discussions with regulators on the full evidence package and approval path continue.
The Protein Imager rendering displays the the cryo-electron microscopy structure of huntingtin (PDB entry 6EZ8).
About Clovertex
Clovertex is an industry leader specializing in meeting the scientific IT needs of pharmaceutical companies, with a robust focus on cloud-based or on-premises cryo-EM processing. As an Advanced Tier Services Partner with Amazon Web Services (AWS), Clovertex leverages its comprehensive expertise to architect, build, automate, and manage software applications designed to meet specific research needs. Our all-encompassing solutions are meticulously tailored to streamline the complex processes associated with pharmaceutical research, underscoring our commitment to innovation, efficiency, and customer satisfaction. By integrating state-of-the-art technology with deep scientific understanding, Clovertex paves the way in optimizing the intersection of information technology and pharmaceutical development.
Useful links
1. Huntington’s disease treated for first time using gene therapy
2. Clovertex website