A single dose of a gene-silencing drug can reverse symptoms of a devastating and incurable inherited brain disorder, scientists have said.
The findings, from animal studies, offer new hope to around 6,700 people in the UK affected by Huntington's disease.There is no effective treatment for the condition, caused by a toxic protein produced by a single defective gene. The disorder leads to uncontrolled movements, loss of mental function, personality changes, and ultimately death. Scientists in the US tested a radical new approach to tackling the disease using a DNA-based "antisense" drug. It works by interfering with and blocking out the protein-making "instructions" from the Huntington's gene.
A single injection of the drug slowed and partially reversed progression of the disease in affected mice and monkeys. Treated animals began moving better within a month, and were physically back to normal within two. Psychiatric improvements, characterised by reduced anxiety, were also seen. The benefits persisted for nine months after treatment, long after levels of the toxic brain protein began building up again. The scientists, whose work is published in the journal Neuron, believe a similar strategy may be effective against other neurodegenerative disorders with a genetic cause. Lead researcher Professor Don Cleveland, from the University of California at San Diego, said: 'Our approach is feasible for development now into a therapy for Huntington's disease in man. 'For diseases like Huntington's, where a mutant protein product is tolerated for decades prior to disease onset, these findings open up the provocative possibility that transient treatment can lead to a prolonged benefit to patients.' The gene responsible for Huntington's, and the protein it produces, are called "huntingtin".
Prof Cleveland added: 'This finding raises the prospect of a 'huntingtin holiday,' which may allow for clearance of disease-causing species (toxic molecules) that might take weeks or months to re-form. 'If so, then a single application of a drug to reduce expression of a target gene could 'reset the disease clock,' providing a benefit long after huntingtin suppression has ended.' The treatment halted the destruction of brain cells and increased life span in mice with a severe form of the disease, the researchers said. It worked equally well whether one or two copies of the Huntington gene were defective. Antisense therapies have already been proven safe in clinical trials and are already the focus of much drug development, Prof Cleveland pointed out.
He said the findings might have implications for other genetic brain diseases and possibly nervous system cancers. Previous attempts to block production of the toxic protein linked to Huntington's have failed because they were aimed at only a small portion of the brain. 'Because huntingtin is widely expressed, targeting multiple brain regions will likely be required for an effective treatment,' said Prof Cleveland. The drug used is based on single strands of DNA called antisense oligonucleotides (ASOs).These bind to and destroy the "messenger" molecules carrying disease-causing instructions from the defective gene. Anyone with a parent who has Huntington's disease has a 50/50 chance of inheriting the faulty gene and developing the disorder. Symptoms normally appear between the ages of 30 and 50, but some people are affected much earlier.
A genetic test is available that can show if someone has the faulty gene, but not the age at which the disease will develop.
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