Using 3D brain organoids, researchers have linked a gene with Huntington’s disease for the first time, which may provide a new target for treatment.

Huntington’s is an incurable neurodegenerative disorder that affects movement, thinking ability and mental health. It is caused by mutations in the HTT gene, which leads to the progressive death of nerve cells in the brain.

In the study, led by EARA member the Max Delbrück Center, Berlin, and Heinrich Heine University (HHU), Dusseldorf, both in Germany, researchers used CRISPR-Cas9 gene editing to make genetic changes to healthy human stem cells, resembling the HTT mutations seen in Huntington’s.

As stem cells are able to develop into any type of cell, the edited stem cells could then be grown into brain organoids that resemble aspects of the early-stage brain.

Analysing the organoids at different developmental stages showed there were lower levels of a particular gene (CHCHD2), which hampered how the nerve cells carried out vital chemical reactions in the brain.

Selene Lickfett, at HHU, discussed whether this effect could be reversed by restoring CHCHD2: “It suggests in principle that this gene could be a target for future therapies.

“The organoid model suggests that HTT mutations damage brain development even before clinical symptoms appear.”