Researchers in the US think they have identified a compound that interferes with the pathogenic effects of Huntington's disease that could lead to the development of a new treatment for the disease as well as making an impact on similar disorders such as Parkinson's disease.
At the moment, there is no cure for Huntington's, a neurodegenerative disorder that now afflicts 30,000 Americans, with another 150,000 at risk. The disease, which is genetically inherited, usually strikes in midlife and causes uncontrolled movements, loss of cognitive function and emotional disturbance.
The compound, provisionally titled B2, was developed by scientists at the Massachusetts Institute of Technology and the Harvard Medical School, and might lead to a drug that could help stop the deadly sequence of cellular events that Huntington's unleashes.
"There are now some drugs that can help with the symptoms, but we can't stop the course of the disease or its onset," said Ruth Bodner, lead author of the paper.
"Depending on its target, any one compound will probably block only a subset of the pathogenic effects," she added.
Huntington's disease is caused by misfolded proteins, called Huntington proteins that aggregate and eventually form large clump-like "inclusions."
The disease is characterised by degeneration in the striatum, an area associated with motor and learning functions, and the cortex.
"The proteins may disrupt the function of cellular structures known as proteasomes, which perform a "trash can" function for the cell - disposing of cellular proteins that are misfolded or no longer needed," said Bodner.
Without a functional proteasome, those cellular proteins accumulate, poisoning brain cells and impairing patients' motor and cognitive function.
Until now, most researchers looking for Huntington's treatments have focused on compounds that prevent or reverse the aggregation of huntington proteins.
However, Bodner said recent evidence suggests that the largest inclusions may not necessarily be harmful and could in fact be protective.
The highest concentration of protein inclusions was found when the researchers applied B2 to cells cultivated in the laboratory. The compound also had a strong protective effect against proteasome disruption, thus blocking one of the toxic effects of the Huntington protein.
The B2 compound also promoted large inclusions and showed a protective effect in a cellular model of Parkinson's disease, another neurodegenerative disorder caused by misfolded proteins.
In Parkinson's disease, the mutant proteins destroy dopamine-producing cells in the substantia nigra. Normally, the dopamine transmits signals to the corpus striatum, allowing muscles to make smooth, controlled movements.
When those dopamine-producing cells die, Parkinson's patients exhibit the tremors that are characteristic of the disease.
Drug treatments are available to help people manage some of their symptoms. There are drugs available to treat abnormal movements. Antidepressants such as fluoxetine (eg. Prozac) can be helpful with depression, and mood stabilisers and antipsychotic drugs can help with some of the emotional disturbances.
The researchers are now working on finding a more potent version of the compound that could be tested in mice.
The study appears online the week of Mar. 6 in the >Proceedings of the National Academy of Sciences (PNAS).