A study gives clues to the origin of Huntington's disease and a new way to find drugs

The first signs of Huntington's disease, an inherited disease that slowly deteriorates the body and mind, do not usually surface until the middle age. But new findings suggest that something in the brain could be hurting before symptoms appear, and sooner than ever before. Thanks to new technology, Rockefeller scientists have been able to trace the causes of the disease in the early stages of development when the brain is just beginning to form.

Developed in the laboratory of Ali Brivanlou, professor to professors Robert and Harriet Heilbrunn, the system uses neuroloids, tiny three-dimensional tissue cultures serving as models for whole organs. The researchers created these clumps of cells from human embryonic stem cells and manipulated them in the laboratory to study the genesis of developmental diseases.

Previous work in the Brivanlou laboratory has revealed cases of occurrence of the disease in young neurons; but this latest study brings even further developmental delay, up to the stage of brain development when cellular uniformity gives way to the emergence of particular structures, process called neurulation. When researchers introduced into neuroloid a mutation known to cause Huntington's disease, it systematically caused dramatic effects with tissue structures of abnormal shape. "Something has collapsed," says Brivanlou.

Researchers have begun to use technology to detect drugs that prevent these abnormalities, an approach that he hopes will provide a powerful alternative to similar work in animal models.

"This technology truly opens the door to identifying the mechanisms that govern brain development, understanding the evolution of the disease, and testing drugs that bring these mechanisms back in the right direction," he said. declared Brivanlou.