An experimental drug has been shown to reduce Huntington’s disease symptoms and extend lifespan in a mouse model. Further research is needed to determine whether these results also apply to humans.
Huntington’s disease, a genetic disease, was previously thought to be incurable. Its clinical symptoms include motor control disorders and psychiatric symptoms. New research offers promising insights. This shows that a particular drug candidate, called anle138b, can significantly reduce the clumps of toxic proteins in the brain that are a hallmark of the disease.
Affected mice treated with the compound remained motile for longer, had less brain shrinkage, and had a longer life span compared to untreated mice. Importantly, this compound not only alleviates symptoms, but also addresses the root cause of the disease by preventing the harmful protein clumps characteristic of the disease from destroying nerve cells and their connections. These results were also confirmed in experiments using human stem cells from Huntington’s disease patients.
Promising therapeutic candidate
These are the key results of a study currently published in the journal EMBO molecular medicine. The research was led by Professor Irina Dudanova, who has been a professor at the First Department of Anatomy and Cell Biology at the University of Würzburg since April 2026, and doctoral student Miguel da Silva Pasilla. The material was developed by a team led by Christian Griesinger, director of the Max Planck Institute for Multidisciplinary Sciences in Göttingen, and Armin Giese from the Ludwig-Maximilians-University of Munich (now MODAG GmbH). Other participants in the study come from the Max Planck Institute for Biointelligence in Martinsried and the University of Cologne.
”Our data demonstrate that specifically targeting toxic protein aggregates with the compound anle138b is a promising approach to stabilize neuronal health in the long term.” commented Irina Dudanova on the research results.
Cellular waste destroys nerve cells
Background: Huntington’s disease is an inherited movement disorder caused by a defect in a specific portion of DNA, the gene that codes for the protein huntingtin. According to health insurance organization AOK, around 10,000 people in Germany are affected by the disease. Hundreds of new cases are diagnosed each year. Faulty repeats in the genetic code (known as CAG repeats) cause the huntingtin protein to assume an abnormal shape and form clumps.
The resulting protein aggregates can be thought of as a type of cellular waste that accumulates within neurons. Protein aggregates interfere with critical cell communication and cause cell death, especially in brain areas involved in movement and cognition. There are no effective treatments that target the underlying cause. This is where the studied compound anle138b comes into play, to prevent the formation of harmful structures.
Researchers investigated the efficacy of anle138b in two different mouse models. One model had a severe early-onset form of the disease, while the other model reflected the genetic status of adult patients. This compound showed beneficial effects in both models.
Huntington’s disease is characterized by loss of the protein PDE10A. This protein is found almost exclusively in nerve cells that die in the disease. The amount of PDE10A decreases dramatically long before patients show their first severe symptoms. “When PDE10A levels decrease, it is a clear signal that the disease is progressing. This protein is therefore very suitable as a biomarker for Huntington’s disease,” explains Miguel da Silva Padilha.
When fewer neurons die, PDE10A levels remain high. This is exactly what scientists have observed. As a result of anle138b treatment, the concentration of PDE10A remained high in both mouse models.
Efficacy proven in human stem cells
An important milestone in this study is the confirmation of these effects in human cells. ”In experiments using induced pluripotent stem cells, or progenitor cells derived from Huntington patient cells, we also observed that the addition of anle138b reduced the amount of Huntington aggregates.” says Irina Dudanova.
This compound is also of interest for the study of other neurodegenerative diseases because it targets a fundamental mechanism of protein aggregation. Similar studies in mouse models have been so promising that a large-scale clinical trial was launched two years ago for the treatment of multiple system atrophy, a Parkinson’s disease-like disease characterized by severe impairment of motor function, balance, and the autonomic nervous system.
sauce:
Julius Maximilian University of Wurzburg, JMU
Reference magazines:
da Silva Padilla, M., Others. (2026). Anle138b improves pathological phenotypes in mouse and cell models of Huntington’s disease. EMBO molecular medicine. DOI: 10.1038/s44321-026-00459-9. https://link.springer.com/article/10.1038/s44321-026-00459-9
