The onset of the rare disease 'Huntington's disease,' in which body parts move involuntarily, has been newly revealed. Domestic researchers have also developed a protein that treats Huntington's disease. A new horizon is opening for Huntington's disease, which has many dark rents(expense).
A joint research team from Harvard Medical School and the Broad Institute announced research results on the 17th (local time) in the international journal 'Cell' that clarify how the genetic mutation causing Huntington's disease occurs.
Huntington's disease is a degenerative brain disease that occurs when brain neurons are damaged. It is nicknamed 'chorea' because body parts move as if dancing when afflicted. In South Korea, as of 2022, there are only 340 patients with this rare disease.
Huntington's disease takes about 15 to 20 years from diagnosis to death. While it has been known that the Huntington gene mutation causes this disease, how specifically the genetic mutation leads to the death of brain cells has not been clarified.
The research team discovered that it takes a long time for the genetic mutation causing Huntington's disease to have harmful effects. They investigated how frequently the three DNA bases (C, A, G) were repeated in neurons from the six individuals who died from Huntington's disease. In most neurons, the repeating numbers of C, A, and G bases were not significantly different from those at birth, but the striatal projection neurons, known to be the first to die in the progression of Huntington's disease, were found to have accumulated far greater repetitions by the time of death.
Neurons accumulate this repeat error when DNA is separated to produce RNA. Problems arise in this process as the DNA strands cannot recombine correctly. Neurons that accumulated over 150 repeats of C, A, and G underwent drastic changes. Initially, they ceased unique gene expressions that distinguished them from other neuron types and lost their identity; later, they activated genes that promote cell death.
The research team found that it took several decades for striatal projection neurons to accumulate enough C, A, and G to become problematic. This is why most Huntington's disease patients develop symptoms between ages 30 and 50. The researchers believe that if they can find treatments to block or delay the problematic accumulation of C, A, and G, it may be possible to delay the onset of Huntington's disease.
Domestic researchers also found proteins that can treat Huntington's disease. Cho Hyunju, a research leader at the Institute for Basic Science (IBS), along with Professor Kim Ho-min of the Korea Advanced Institute of Science and Technology (KAIST) and Professor Lee Sung-bae of the Daegu Gyeongbuk Institute of Science and Technology (DGIST), announced that they have developed an effective therapeutic Chaperone for Huntington's disease.
Chaperone plays a role in maintaining the homeostasis of proteins. It facilitates proper three-dimensional folding of proteins within cells and prevents the aggregation of misfolded proteins, allowing them to function properly.
The research team induced random mutations in PEX19, one of the membrane protein Chaperone, and created a library of hundreds of thousands of variants. They selected these variants using yeast toxicity-based screening techniques to develop the mutant Chaperone PEX19-FV, which inhibits the toxicity of the huntingtin protein. PEX19-FV successfully blocked the interactions between huntingtin proteins.
The researchers confirmed the effectiveness of PEX19-FV through experiments with fruit flies. When they expressed PEX19-FV in flies with overexpressed huntingtin protein, which showed neurodegenerative symptoms, the ability to climb up the walls of the test tubes improved by about two times, greatly enhancing their motor skills. Additionally, the average survival rate of the fruit flies increased by about three times.
Culturing neurons extracted from mouse brains and expressing PEX19-FV alongside huntingtin protein resulted in a reduction of severe structural damage in the neurons from about 80% to below 5%, and a decrease in neuronal death by about ten times.
Research leader Cho Hyunju noted that "the mutant Chaperone developed through this research can effectively inhibit the aggregation of huntingtin protein, protecting neurons," and added, "By appropriately modifying existing Chaperones, it may be possible to treat not only Huntington's disease but also various degenerative neuro diseases." The research team plans to develop therapeutic Chaperones that can be used for treating degenerative neuro diseases based on their research results.
Reference materials
Cell (2025), DOI: https://doi.org/10.1016/j.cell.2024.11.038
Nature Medicine (2025), DOI: https://doi.org/10.1038/s41591-024-03424-6
Nature Communications (2025), DOI: https://doi.org/10.1038/s41467-025-56030-6