Good story:

 

http://www.abc.net.au/catalyst/stories/2879914.htm

 

Professor Steve Wilton
This is the ultimate personalised medicine. This could be huge.

Lesley Murphy
It’s actually extremely exciting from a personal point of view.

Professor Susan Fletcher
It really has opened the floodgates.

NARRATION
The enthusiasm is over a new kind of medicine, that helps correct genetic mistakes. It’s not genetic engineering, rather something quite ingenius: a patch to fill in for faulty genes.

Prof. Susan Fletcher
Ultimately most diseases have a genetic origin, even infections. I mean infections can be regarded as an acquired genetic disease.

Prof. Steve Wilton
This has enormous implications to a variety of conditions. Cancer, asthma, Alzheimer’s, diabetes.

NARRATION
But right now, the researchers are using their method for a much rarer genetic illness – a form of muscular dystrophy known as Duchenne. It’s a cruel disease. Conor Murphy was diagnosed at age three.

Lesley Murphy
Well there isn’t the words to describe what it’s like to be told that your child has got Duchenne. Your child has a condition which is untreatable, no cure. Nothing.

Conor Murphy
There’s days where you know you just don’t feel like getting up at all, like what’s the point kinda thing, but they don’t happen that often.

Lesley Murphy
It’s a pretty sad day when you come to realise that you wish your child had cancer. At least if they had cancer they’d be able to go to doctors' appointments, have therapies, have treatments, they still might not survive but you’ve got something, you’ve got hope.

Prof. Susan Fletcher
It’s an horrendous thing to be confronted with, families often go into shock and it affects the whole family. The disease is going to steal away his muscles, it's then going to steal his independence and then steal his life.

NARRATION
Part of the cruelty is nothing seems wrong in the beginning.

Prof. Steve Wilton
The boys look perfectly fine to start with. They have muscle damage, but the repairers of the young muscle keeps up with the degeneration. By the age of three to five years of age, parents start to notice the kids are a little bit slower than normal.

Prof. Susan Fletcher
The boys become weak. They lose the ability to walk by the age of 12, usually an electric wheelchair by maybe 12, 13, 14.

Prof. Steve Wilton
In the absence of good health care and maintenance, 90 per cent would be dead before they’re 20, they’re literally just too weak to breathe.

Lesley Murphy
And every day you grieve a little more, everyday your child loses the ability to do something else. It might only be a miniscule thing, but weekly, monthly, you see them deteriorating... dying, dying before your eyes and there is absolutely nothing you can do.

NARRATION
It’s usually males who get Duchenne, because the genetic mistake is on the X chromosome. Because females have two X chromosomes, they can normally compensate for the genetic error. The mistake is in just one gene.

Prof. Steve Wilton
The gene is called dystrophin and this is the largest gene in the human body, it really is an accident waiting to happen, it’s almost point one per cent of our genetic makeup.

NARRATION
An accident waiting to happen because the genetic machinery is so complex, a mistake in large genes occur from time to time.But remarkably, the Perth researchers have come up with a way to reprogram the body’s machinery, to work around the genetic mistake. It’s called exon skipping. And their work’s sufficiently advanced for the first human trials to begin in London. Sam Cornelius is in the trial. He’s 11 and hasn’t got to the wheel chair stage yet, but he has to endure painful stretching exercises every day.

Mrs Cornelius-Light
They’ve discovered that physio really helps this condition and that once the muscle has tightened, it's very difficult to get that muscle use back again. By keeping the muscles stretched every day it just stops them from tightening too quickly.

NARRATION
The trial was to see if the Perth scientists’ exon skipping treatment was safe and might have an effect.

Sam Cornelius - Light
They done a few blood tests first of all and they done a skin biopsy which hurt a little bit and then they put me to sleep and I had the injection put in my leg.

NARRATION
The medicine injected would act like a software patch.

Dr Graham Phillips
When there’s a defect in your computer’s operating system, a software patch is downloaded to fix it. Now wouldn’t it be wonderful if we could do something similar for defect in our genes. Well that’s just what’s being tested out here.

NARRATION
The problem for children with Duchenne is their gene error means a particular protein is not being made properly.

Prof. Steve Wilton
The gene acts to a code protein called dystrophi, which acts like a molecular shock absorber, giving strength and stability to muscle fibres.

NARRATION
Given muscle is involved in almost every body process, faulty dystrophin affects virtually everything. These scientifically accurate graphics show how the body’s dystrophin gene makes the protein. The gene’s corresponding stretch of DNA is read by the blue polymerase molecule shown here in blue. A copy of the information is made in the form of an RNA molecule. Unfortunately, the genetic mistake is copied too. The RNA, in turn, is read to make the protein.

Prof. Steve Wilton
Literally, it reads three letters at a time. These are called codons. It’s like a ticker tape machine. And these build up a protein. So you can see a protein being extruded.

NARRATION
But the genetic mistake means the dystrophin protein, shown here in red, is not built up properly. And that’s where the researchers’ ingenious software patch comes in. The patch is actually a small piece of the basic molecule DNA and RNA are made of nucleic acid. Using the chemical building blocks for nucleic acids, the scientists tailor make one to patch over the genetic mistake.

Dr Graham Phillips
This amazing machine can produce any piece of nucleic acid you want. All you do is enter in the letters – A G C – in the right order. It puts them together and produces the product.

NARRATION
Today, the Cornelius family have come to find out the results on the product injected into Sam. It’s early days yet, and this is a preliminary trial, but the message is positive.

Professor Francesco Muntoni
The results have shown that the children who received the height dose had also protein production. So they were able to produce some dystrophin.

NARRATION
Analysis of the patients’ muscle biopsies clearly showed new dystrophin protein had been made. Sam is now waiting for the next step: a full body infusion of the molecular patch to see if it can slow his deterioration.

Prof. Steve Wilton
Half the kids that were alive when I first started this work have now succumbed to their disease. I can’t afford to wait, I refuse to wait another 10 years for this therapy to get to more people.

Conor Murphy
It might not help me, I’m probably past the point of being able to walk again. But if it just gives me, you know, using my arms a bit more so I can scratch my head and take myself to the toilet or whatever, that way I won’t need many as much help as I get now. No point getting all annoyed and crying about it or whatever, because it’s not going to change anything. So you just get on with it.

NARRATION
Back in England, the next phase of trials for Sam should begin later this year. And in the coming years, as we find out more about the genetics of disease, the exon skipping technique could be used to treat a whole host of illnesses.

Topics: Health
  • Reporter: Dr Graham Phillips
  • Producer: Dr Graham Phillips
  • Researcher: Dr Holly Trueman
  • Camera: Ricky Harvey, Scott Munro
  • Sound: Gary Carr, Chris Sheedy
  • Editor: Andrew Scott

Story Contacts

Professor Steve Wilton
Winthrop Professor, University of Western Australia
President, Australian Gene Therapy Society
Head, Molecular Genetic Therapy
Centre for Neuromuscular and Neurological Disorders
Australian Neuromuscular Research Institute

Professor Sue Fletcher
Centre for Neuromuscular and Neurological Disorders
Australian Neuromuscular Research Institute

Lesley and Conor Murphy

The Cornelius-Light family

 

 

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Replies to This Discussion

Good film Ofelia! It simplifies exon skipping and shows how it works. I loved the graphics and storyline. Let's get on to real life exon skipping and quickly.
Am I understanding this correctly that it would work for any child doesn't depend on which exon is missing? This is also a different company than the AVI and Prosensa? This does sound amazing and great!
This is owned by Prosensa/GSK and AVI. They are the only two using skipping for Duchenne. It truely is very amazing and great Kristi!!

It will work well on a lot of exons but not all, and is mutation specific. They have to mix a slightly different cocktail for every different exon(s) they want skipped, there is no "one size fits all exons". This approach, therefore, is highly personalized, tailored to fit and considered groundbreaking compared to how people are taking medicine these days. Clinical trials are currently underway for skipping exon 51.

Kristi Koop said:
Am I understanding this correctly that it would work for any child doesn't depend on which exon is missing? This is also a different company than the AVI and Prosensa? This does sound amazing and great!

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