Huntington’s breakthrough as experts find way of killing mutant protein

Huntington’s breakthrough as experts find a way of killing the mutant protein which causes the irreversible brain damage

  • Chinese researchers found four compounds that can clear the mutant protein
  • The mutant type of huntingtin is behind the crippling condition and kills neurons
  • The technique has only been proven to work on human cells, mice and flies 

Hope has been raised for thousands of Huntington’s patients after scientists found a potential way of treating the cruel disease.

Chinese researchers found four compounds that can clear the mutant protein behind the crippling condition, which kills vital brain cells.

Their technique was only proven to work on human cells, mice and flies – but could open the door for the first ever human treatment.

Scientists have for years tried to cut levels of the mutant protein behind the condition (red) without simultaneously clearing their wild counterparts (blue), which are vital for brain health. Chinese researchers found four compounds (orange) that bind to the mutant protein and a crucial component of the neuron’s internal mechanism (light blue) for clearing out invaders

Huntington’s impairs the central nervous system and leads to involuntary movements, difficulty talking and even memory loss.

On average, patients live for between 10 and 20 years after their diagnosis. The NHS says there is currently no way to stop it getting worse.

The incurable condition, which strikes 8,500 adults in the UK and around 30,000 in the US, occurs as a result of a fault in the huntingtin gene.

This leads to a build-up of the mutant huntingtin protein in neurons, causing them to die and triggering the devastating symptoms.

Scientists have for years tried to cut levels of the protein without simultaneously clearing their wild counterparts, which are vital for brain health.

But until now, researchers had struggled to make headway. The new findings are published in the prestigious journal Nature.

WHAT IS HUNTINGTON’S? 

Huntington’s disease is an illness caused by a faulty gene in your DNA (the biological ‘instructions’ you inherit which tell your cells what to do).

On average, patients live for between 10 and 20 years after their diagnosis. The NHS says there is currently no way to stop it getting worse.

The incurable condition, which strikes 8,500 adults in the UK and around 30,000 in the US, occurs as a result of a fault in the huntingtin gene.

Huntington’s can cause changes with movement, learning, thinking and emotions. Once symptoms begin, the disease gradually progresses, so living with it means having to adapt to change, taking one day at a time. 

Huntington’s is not something you can catch; it is inherited. Every child conceived naturally to a parent who carries the Huntington’s gene has a 50 per cent chance of inheriting it.

Fudan University academics conducted several tests to find compounds that could clear the mutant protein without affecting the normal one.

Dr Boxun Lu and team found four promising ones, which reduced levels of the faulty huntingtin and had no impact on the other in all of the trials.

Tests on human neurons showed fewer of them died when exposed to the molecules – dubbed 10O5, 8F20, AN1 and AN2.

Flies bred to have Huntington’s and given the treatment were better able to climb and survived longer, compared to their untreated counterparts.

And mice with the rodent equivalent of the condition also saw a benefit – they performed better on tests of their motor function than mice not treated.

Experts not involved in the research, including Dr Huda Zoghbi of Houston’s Baylor College of Medicine, have welcomed the study.

She said future trials should look for any ‘off-target effects’, including whether the compounds inadvertently clear any other vital proteins.

‘Even effects that initially seem inconsequential might build up over the course of long-term therapy, becoming as problematic decades later as the original toxic protein,’ she said.

But Dr Zoghbi, writing in a linked editorial, added the evidence was ‘encouraging’ and said the treatment produced ‘functional improvements’.

The compounds bind to the mutant protein and a crucial component of the neuron’s internal mechanism for clearing out invaders.

Professor John Hardy, a neuroscientist at University College London, said the study was ‘interesting’ but a long way from clinical trials. 

Dr Edward Wild, of UCL’s Huntington’s centre, said: ‘Unfortunately, so far, nothing that has worked in a mouse model has slowed the disease in patients.

‘So it is important to study these new drugs thoroughly to get the best possible idea of whether the approach is safe and effective enough to be taken forward to human trials.’ 

Professor Tara Spires-Jones, of the University of Edinburgh, said: ‘This is an interesting and potentially important paper.’ 



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