"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, a postdoctoral fellow in Massachusetts Institute of Technology’s Center for Cancer Research.
The newly developed compound might lead to a drug that could help stop the deadly sequence of cellular events that Huntington's unleashes. "Depending on its target, any one compound will probably block only a subset of the pathogenic effects," Bodner said.
Huntington's disease is caused by misfolded proteins, called huntingtin proteins, that aggregate and eventually form large clump-like "inclusions." The proteins may disrupt the function of cellular structures known as proteasomes, which perform a "trash can" function for the cell, said Bodner.
Until now, most researchers looking for Huntington's treatments have focused on compounds that prevent or reverse the aggregation of huntingtin proteins. However, recent evidence suggests that the largest inclusions may not necessarily be harmful and could in fact be protective, said Bodner. So, the scientists decided to look for compounds that actually promote the formation of large inclusions.
The highest concentration of protein inclusions was found when the researchers applied a compound they called 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 huntingtin 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.
The researchers are now working on finding a more potent version of the compound that could be tested in mice.
MEDICA.de; Source: Massachusetts Institute of Technology