Caused by a lack of a gene which produces an enzyme that breaks down certain carbohydrates, the disease results in a build-up of the carbohydrate in cells – and has no cure. It triggers problems ranging from distorted facial features and heart abnormalities, as well as brain and thinking problems.
“Many are in wheelchairs… dependent on their parents until they die,” said Dr Chester Whitley, a genetics expert at University of Minnesota.
Madeux himself, has had 26 operations to date – to fix everything from hernias to bones pinching his spinal column.
“It seems like I had a surgery every other year of my life” and many procedures in between, he said. Last year, he nearly died from a bronchitis and pneumonia attack. “I was drowning in my secretions – I couldn’t cough it out,” he said.
Currently, he relieves his symptoms through weekly IV doses of the enzyme – at a hefty cost, ranging from USD100,000 to USD400,000 per year. Even so, the influxes of enzymes cannot repair any existing damage or stop further deterioration of the brain.
The nitty-gritty detailsMadeux is in a bit of luck. He is the first patient to receive Sangamo Therapeutics’ experimental gene therapy. The therapy sees Madeux injected with viruses containing DNA instructions for two zinc-finger proteins – which act like molecular scissors – to seek the faulty DNA, make an incision and insert the missing gene. The virus was altered, so it did not cause infection and travelled straight to the liver. Billions of copies of the virus were fed through the IV. The cells make the zinc fingers, which then cut the DNA and the new gene is slipped into the right place and ready to make the missing enzyme.
“Only 1% of liver cells would have to be corrected to successfully treat the disease,” explained Madeux’s physician and study leader, Dr Paul Harmatz. Nonetheless, there is no guarantee the treatment will work – or work without side effects.
It will take one month to see signs of success and three months to fully assess its functionality. If it works – it will be the first time that gene therapy has worked from inside a human body.
“It’s kind of humbling” to be the first to test this, expressed Madeux. “I’m willing to take that risk. Hopefully, it will help me and other people.”
Carefully taking irreversible, but vital steps“How bulletproof is the technology? We’re just learning,” said Dr Carl June, a scientist at University of Pennsylvania, who has done gene therapy work.
The therapy has gone through rigorous testing to ensure its safety and the results have been positive. For example, the virus is built in such a way that it cannot enter eggs or sperm and therefore, has the potential to be passed onto the next generation.
In addition, the zinc-finger nucleases reduce the possibility of the gene being inserted into the wrong place. However, there is no ‘backspace’ or ‘delete’ button. Yet, experts still think this is a valuable experiment.
“You’re really toying with Mother Nature” and the risks can’t be fully known; but, the studies should move forward because these are incurable diseases, said one independent expert, Dr Eric Topol of the Scripps Translational Science Institute in San Diego.
Dr Howard Kaufman, a Boston scientist at the National Institutes of Health (NIH), who was involved in the approval of the study, echoed in agreement – stating that the promise of gene editing is too great to ignore.
“So far, there’s been no evidence that this is going to be dangerous,” he reasoned.
Template treatment of the future?Majority of the scientific community agrees.
Last June, the NIH has approved the use of CRISPR technology as cancer treatment, and the University of Pennsylvania is already trialling this.
Jennifer Doudna, one of the scientists credited with the discovery of CRISPR, hoped that many genetic diseases can be addressed moving forward. Especially for sickle cell anaemia and cystic fibrosis, Doudna believed there is much potential since the technology available today is sufficiently able to cure the defect in cells cultured in the lab. It is therefore just a question of bridging the gap so it can be performed clinically and safely.
“When I think about what makes me nervous about this technology, it really comes down to how little we really understand the function of genes, especially the interactions between genes in our own genomes,” said Doudna.
Perhaps, in three months, the experiment on Madeux will provide some much sought-after answers. MIMS
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