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Scientists led by Lawrence Berkeley National Laboratory report that Huntington's disease is driven not only by the known genetic mutation but by a sharp rise in breaks across DNA strands throughout the genome.
The study, published in Nature Communications, found that the mutant huntingtin protein suppresses DNA repair enzymes, so double-stranded breaks accumulate before symptoms appear.
In transgenic mice, an investigational mitochondria-targeted antioxidant reduced those breaks, prevented motor deficits and lowered brain inflammation.
Because compounds acting on this pathway already exist, the finding points to a faster route to therapy than three decades of work aimed at the mutation itself.
Huntington's disease is a rare, incurable, autosomal dominant neurodegenerative disorder affecting an estimated 3 to 7 people per 100,000, usually beginning between ages 30 and 50.
Huntington's disease is caused by a mutation in the HTT gene on chromosome 4 - specifically an expansion of a repeated CAG trinucleotide sequence. Because the disorder is autosomal dominant, a single copy of the faulty gene is enough, which is why a child of an affected parent has a 50 per cent chance of inheriting it. The HTT gene codes for a protein called huntingtin whose exact function remains unclear, though it is believed to support the working of nerve cells; when the repeat is too long, the protein folds abnormally and destroys neurons. For three decades the therapeutic effort concentrated on the mutation and its expanding repeat, without producing a treatment. The Berkeley Lab work argues for a two-stage picture: the faulty protein also suppresses the cell's DNA repair enzymes, so double-stranded breaks pile up genome-wide - and that damage, not the repeat expansion alone, tracks with the onset of disease. Treat the damage and, in the mouse model at least, the animals stayed well.
Simple Analogy: A factory has both a fault on the production line and a maintenance crew. The disease research has spent thirty years on the fault; this study finds that the faulty part has also been quietly locking the maintenance crew out of the building - and that letting them back in keeps the factory running.
GS Paper III > Science and Technology: Biotechnology, Genetics and Health
General Science > Biology: Genetics and Human Diseases
Which of the following bacteria is responsible for causing "Typhoid"?
Answer: Salmonella typhi
An inheritance pattern in which one copy of the altered gene, on a non-sex chromosome, is sufficient to cause the disorder - giving a child of an affected parent a 50 per cent risk.
The protein encoded by the HTT gene; its precise function is unclear, but it is thought to support nerve-cell function, and its mutant form misfolds and destroys neurons.
A group of structures deep in the brain that regulate movement; their degeneration produces the chorea characteristic of Huntington's disease.
Involuntary, irregular, dance-like movements - the visible hallmark of Huntington's disease, from the Greek for dance.
A cut through both strands of the DNA double helix; the most dangerous form of DNA damage, and the lesion found to accumulate in this study.
Chemically reactive oxygen-containing molecules produced in cells, which damage DNA, proteins and membranes when not neutralised by antioxidants.