When a group of campus researchers induced the symptoms of Huntington’s disease — a fatal genetic disorder that claims millions of lives every year — in the cells of roundworms, the last outcome they expected was weight gain.
Yet the mysterious fat causing nematodes to swell might also invigorate human cells against the degenerative effects of Huntington’s and a string of other baffling diseases for which no cures currently exist, such as Alzheimer’s and Parkinson’s. The researchers’ findings were published online Thursday in Cell magazine.
“It’s not like we set out to do this — it sort of found us,” said Andrew Dillin, a UC Berkeley molecular and cell biology professor and co-author of the study. “Fortuitously, we knew the cells were getting fat and the animals were getting fat, and we could have ignored that but we put the two together.”
Huntington’s disease induces mass brain cell deterioration resulting from misfolded proteins that clump together inside neurons, according to Milos Simic, a campus graduate student who co-authored the study. It causes patients to suffer from motor dysfunction, dementia and mood changes.
Though Huntington’s is not typically diagnosed until affected patients are in their 40s and 50s, the disease is “100 percent lethal,” according to Dillin.
A key discovery from the study concerned the internal workings of the mitochondria — the powerhouses of the cell, which have been implicated in previous disease research — that play a crucial role in the progression of neurodegenerative disease.
Researchers found that abnormal aggregates of the disease actually latch onto the mitochondria, flooding the cell interior with “chaperone” proteins in response to the misfolded, disease-causing proteins. One of these “chaperone” proteins also triggers fat accumulation in worms, improving protein folding and potentially protecting organisms from the effects of the disease.
According to Simic, manipulating this response at different stages of disease progression could open the door to fine-tuned treatment methods. Dillin noted, however, that while the researchers were the first to link fat molecules with Huntington’s disease progression, the precise way that fat curbs protein aggregates in cells remains unclear.
“Huntington’s is devastating — we know the cause, we can diagnose it, (but) we cannot prevent it, slow it down or reverse it,” said campus adjunct genetics professor Fyodor Urnov, who was not affiliated with the study. He added that the scientific community must be more adventurous and perform “riskier undertakings” to bolster the number of effective treatment therapies.
According to Dillin, nearly all neurodegenerative diseases are currently incurable because patients often don’t seek treatment until conditions have progressed into advanced stages, and the brain is among the most difficult organs for therapeutic drugs to access.
Urnov said pinpointing a detailed molecular pathway of Huntington’s disease is the only way to combat it. He noted that treating the disease would require a multi-faceted approach — a combination of potential drug candidates and ample research funding — but that progress had been made toward solving other conditions, such as cystic fibrosis.
Dillin said the group plans to test the effects of the fat on an animal model, as well as on diseases such as Alzheimer’s, in future research.
“Huntington’s has been an incredibly hard problem, and I’m glad that hasn’t discouraged people from going after it,” Urnov said. “You have to chisel away at it until it cracks.”