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The study, published in Nature Metabolism, has shown for the first time the biochemical change responsible for the development of Huntington’s disease, and how blocking this change stopped disease progression.
Huntington's disease is an inherited condition that stops parts of the brain from working properly, leading to mental and physical decline that slowly worsens over time. The symptoms usually begin to appear after the age of 30 years and are fatal, but this can be after a period of up to 20 years, during which they worsen.
The study explores how an early change described in the brain of HD patients in the early 1980s could lead to Huntington's disease onset. The researchers identified that problems with specific neurons in the brain, called indirect pathway spiny projection neurons (iSPNs), which are the initially affected cells in HD, may trigger an imbalance in dopamine levels upon missing an important signalling derived from the activation of the neurotrophin receptor TrkB. This imbalance is linked to early symptoms of the disease, such as abnormal, involuntary movements.
First the researchers looked at mice that lacked normal function in these iSPNs due to disrupted TrkB neurotrophin signalling and noticed that they showed increased levels of dopamine in the brain, leading to hyperactivity. This change occurred before noticeable symptoms appeared, suggesting that these early alterations may contribute significantly to HD progression.
Read the full story on the University of Oxford website.