Huntington’s disease (HD) is a hereditary movement disorder caused by a CAG repeat expansion in the huntingtin gene. HD is characterized by deposition of mutant huntingtin (mHTT) aggregates, and by severe neurodegeneration of the basal ganglia and neocortex. No cure is currently available, and new treatment options are urgently needed. Here, we show that the oligomer modifying molecule anle138b (INN: emrusolmin) improves multiple disease phenotypes in cell culture and in two mouse models of HD. Application of anle138b reduced mHTT aggregate formation and ameliorated neurotoxicity in primary neurons. Oral administration of anle138b delayed deposition of mHTT inclusions, reduced brain atrophy, mitigated neuroinflammation and transcriptional alterations, improved motor function and extended life span in HD mice. Downregulation of striatal markers and synapse loss in striatal spiny projection neurons were also partially rescued. No adverse effects of anle138b were observed in wildtype animals. Moreover, anle138b markedly decreased mHTT aggregation in human neural precursor cells differentiated from HD patient-derived induced pluripotent stem cells (iPSCs). Altogether these results illustrate the potential of anle138b as a disease-modifying treatment for HD.

In a mouse model of Huntington’s disease, targeted modulation of neuronal activity restores network function and improves motor deficits.

Huntington’s disease (HD) is a hereditary movement disorder caused by a CAG repeat expansion in the huntingtin gene. HD is characterized by deposition of mutant huntingtin (mHTT) aggregates, and by se...

A common feature of neurodegeneration is selective vulnerability, where certain neurons succumb to disease, while others remain spared. The molecular underpinnings of these differences remain elusive....

Our Group Our newly established research group at ISTA is seeking a postdoctoral researcher to work on an ERC-funded project- HypoAdapt. We study how the brain controls bodily responses to environm...

Individual behaviours require the nervous system to execute specialised motor programs, each characterised by unique patterns of coordinated movements across body parts. Deep learning approaches for b...

We are looking to support our rapidly growing team as soon as possible:

The accumulation of protein aggregates has been causatively linked to the pathogenesis of neurodegenerative diseases. In this study, we have conducted a genome-wide CRISPR-Cas9 screen to identify cell...

Huntington′s disease (HD) is a devastating movement disorder without a current cure. Although the monogenic basis of HD is well-defined, the complex downstream effects that underlie behavioral symptom...

Huntington′s disease (HD) is a devastating movement disorder without a current cure. Although the monogenic basis of HD is well-defined, the complex downstream effects that underlie behavioral symptom...