The defect that causes a rare form of incurable genetic brain disease, Huntington's, has been corrected in patients for the first time.
Huntington's, an inherited neurological condition, affects the brain and nervous system with current treatments only targeting symptoms and not the cause of the irreversible brain damage.
British scientists at University College London have conducted a trial on 46 men and women in the early stages of Huntington's across the UK, Canada and Germany.
The patients were given four spinal injections one month apart with the amount increased with each injection.
Roughly a quarter of participants formed the control group and were given a placebo injection.
The results showed a correlation between the amount of drug given and the reduction in the concentration of the harmful protein causing Huntington's in the spinal cord fluid.
"The results of this trial are of groundbreaking importance for Huntington's disease patients and families," the chief investigator of the research, Professor Sarah Tabrizi, said.
"For the first time a drug has lowered the level of the toxic disease-causing protein in the nervous system and the drug was safe and well-tolerated.
"The key now is to move quickly to a larger trial to test whether the drug slows disease progression."
Professor Tabrizi said the next trial would look at the impact on symptoms over a one- or two-year period.
If that trial is successful, the drug could be used to treat people with the gene for Huntington's to prevent the disease from occurring.
The treatment works by using a synthetic single strand of DNA to attach to the messenger molecule before it forms into a protein capable of destroying brain cells.
Professor John Hard, who won the Breakthrough Prize for his work on Alzheimer's, hailed the research as a milestone.
"I really think this is, potentially, the biggest breakthrough in neurodegenerative disease in the past 50 years," he told the BBC.
Researchers say the synthetic strand could be customised to target other proteins in the treatment of other forms of dementia like Alzheimer's.
UCL sicentist Ed Wild, who administered the drug in the trial, said he was quietly optimistic the drug could potentially be used to treat the amyloid proteins in Alzheimer's sufferers.
"I don't want to overstate this too much, but if it works for one, why can't it work for a lot of them? I am very, very excited," he told the Guardian.
Professor Giovanna Mallucci, who is associate director of UK Dementia Research Institute at the University of Cambridge, welcomed the findings.
But she said the transferability to Alzheimer's treatment is not so "clear-cut".
"The case for these is not as clear-cut as for Huntington's disease, they are more complex and less well understood," she told the BBC.
"But the principle that a gene, any gene affecting disease progression and susceptibility, can be safely modified in this way in humans is very exciting and builds momentum and confidence in pursuing these avenues for potential treatments."
The full findings from the trial will be published next year.
The drug therapy was developed by Canadian company, Ionis Pharmaceuticals, who has now sold the licence to Swiss pharmaceutical company Roche for US$45 million.
In Australia, more than 1,800 people have the disease and approximately 9,000 are at risk, according to Huntington's New South Wales.
Most cases are genetic, but 10 per cent of patients do not have a family history.
A parent with Huntington's gene has a 50 per cent chance of passing the disease gene onto their children.