BOSTON — Scientists are unraveling the mystery of what triggers Huntington’s disease, a devastating and fatal hereditary disorder that strikes in the prime of life, causing nerve cells in parts of the brain to break down and die.
They focused on the Huntington’s mutation, which involves a stretch of DNA in a particular gene where a three-letter sequence – CAG – is repeated at least 40 times.
Recently, experimental drugs designed to lower levels of the protein produced by the mutated Huntington’s gene have struggled in trials.
Slowing or stopping the expansion of DNA repeats may be a better way to target the disease, researchers said.
Though there are no guarantees this would stave off Huntington’s, McCarroll said “many companies are starting or expanding programs to try to do this.”
BOSTON — Researchers are trying to figure out what causes Huntington’s disease, a terrible and deadly genetic condition that damages and kills nerve cells in certain areas of the brain when a person is in their prime.
Although the genetic mutation associated with Huntington’s disease has long been known, scientists have yet to figure out how individuals with the mutation could be born with it and not experience any issues until later in life.
Surprisingly, new research reveals that the mutation is safe for decades. However, it gradually develops into a more significant mutation until it finally surpasses a threshold, produces harmful proteins, and destroys the cells in which it has spread.
“If the gene is present at conception, why do you have a genetic disorder that manifests later in life?” asked Dr. Dot Mark Mehler, who is not involved in the study but leads the Institute for Brain Disorders and Neural Regeneration at the Albert Einstein College of Medicine. “It addresses a lot of the issues that have plagued the field for a long time,” he said, referring to the survey as a “landmark” study. “,”.
The death of brain cells eventually causes issues with thinking, behavior, and movement. Involuntary movement, unsteady gait, personality changes, and impaired judgment are some of the symptoms of Huntington’s disease that usually start between the ages of 30 and 50 and get worse over the course of 10 to 25 years.
Researchers from Harvard Medical School, McLean Hospital in Massachusetts, and the Broad Institute of MIT and Harvard examined half a million cells from brain tissue donated by 50 individuals without Huntington’s disease and 53 with the disease.
They concentrated on the Huntington’s mutation, which occurs when a specific gene’s DNA contains a three-letter sequence, CAG, repeated at least 40 times. This sequence is only 15–35 times repeated in healthy individuals. Over time, they found that DNA tracts containing 40 or more of these “repeats” grow to be hundreds of CAGs long. A threshold of roughly 150 CAGs causes some neuron types to become ill and die.
Steve McCarroll, a member of Broad and co-senior author of the study, said the results “were really surprising, even to us.” The study was published Thursday in the journal Cell. The Howard Hughes Medical Institute, which also funds the Associated Press Health and Science department, provided some funding for the study.
Repeat tracts grow slowly for the first twenty years of life, then rapidly when they reach about 80 CAGs, according to the research team’s estimation.
One of the senior authors of the study, neuroscience researcher Sabina Berretta, stated, “The longer the repeats, the earlier in life the onset will happen.”.
Because prior research indicated that repeat expansions in the range of 30 to 100 CAGs were required — but not sufficient — to cause Huntington’s disease, researchers acknowledged that some scientists were initially dubious when results were presented at conferences. While McCarroll acknowledged that expansions with 100 or fewer CAGs are insufficient to cause the disease, he said his research revealed that expansions with at least 150 CAGs do.
About 41,000 Americans suffer from the incurable condition, which is currently managed with medication to control its symptoms. Researchers hope their findings will help scientists develop ways to delay or prevent the condition.
Recently, trials of experimental medications intended to reduce the amount of the protein generated by the Huntington’s gene mutation have been difficult. According to the latest research, this is because very few cells ever contain the harmful form of the protein.
Researchers suggested that a more effective strategy to combat the illness might be to slow or halt the growth of DNA repeats.
There is no assurance that this would prevent Huntington’s disease, but “many companies are starting or expanding programs to try to do this,” McCarroll said. “.
The Science and Educational Media Group at the Howard Hughes Medical Institute and the Robert Wood Johnson Foundation provide support to the Associated Press Health and Science Department. All content is the exclusive responsibility of the AP.