A discovery made by researchers at the University of Oxford could help to stop the progression of a disease which causes mental and physical decline.

Huntington's disease is an inherited condition that causes this decline by affecting the brain.

Symptoms begin after the age of 30 and worsen over time, with the disease ultimately being fatal.

In their new study, the Oxford researchers have identified a key biochemical mechanism linked to the development of the disease.

This breakthrough could allow the disease to be studied before clinical onset, and potentially for its progression to be halted.

The study is the first to reveal the biochemical change responsible for the development of Huntington’s disease, and how blocking this change can stop its progression.

Liliana Minichiello, professor of cellular and molecular neuroscience at Oxford’s department of pharmacology, and the study's lead author, said: "The big problem with Huntington’s disease is that by the time that symptoms develop, much of the damage has already been done, and therefore, it is fundamental that we understand the changes that occur before the disorder develops if we are to develop effective therapeutics.

"This research marks the first time that we have been able to identify a specific chemical change that is unique to the development of Huntington’s disease, which opens the possibility of developing new tests to study the early changes of the disease before irreversible damage occurs.

"Understanding these early changes provides crucial insights into how Huntington’s disease develops, and this knowledge could help develop preventive therapies to maintain dopamine balance and delay or halt disease progression."

The study explores how an early change described in the brain of patients with the disease in the early 1980s could lead to its onset.

The researchers found issues with specific neurons in the brain, known as indirect pathway spiny projection neurons (iSPNs), might cause a dopamine imbalance when missing a vital signal from the neurotrophin receptor TrkB.

This imbalance is linked to early symptoms of the disease, such as abnormal, involuntary movements.

The researchers found mice lacking normal iSPN function due to disrupted TrkB signalling had increased dopamine levels and hyperactivity.

This change occurred before visible symptoms appeared, suggesting these early changes may play a significant role in Huntington's disease progression.

They also discovered a protein called GSTO2, an enzyme involved in the glutathione metabolism, is crucial in regulating dopamine levels.

By selectively reducing the activity of this protein in mice, the researchers were able to prevent dopamine and energy metabolism dysfunction, stopping the onset of motor symptoms in mice.

The enzyme shows similar dysregulation in a rat model of Huntington's disease and some rare brains of asymptomatic patients.