TWO people from Donegal suffering from amyloidosis were among the first in the world to receive a groundbreaking gene editing drug that has the potential to offer a cure for the horrific disease. James Green, Burt and Patrick Doherty, Gaoth Dobhair took part in the first phase of a clinical trial led by the UCL National Amyloidosis Centre at the Royal Free Hospital in London.

Amyloidosis is caused by the build up of an abnormal protein in the body’s tissues and organs.  It causes heart failure and nerve damage leading to paralysis, incontinence and wasting and it severely impairs virtually all aspects of daily living. The condition, which is ultimately fatal, is so prevalent in Donegal that it is also known as ‘Donegal Amy’.

Patients of the trial received a one-off infusion of a molecule known as CRISPR/Cas 9. The use of CRISPR allows scientists to make very precise changes in DNA.
James and Patrick were among the first six patients to receive  the treatment. The results, which have been published in the New England Journal of Medicine, showed production levels of the abnormal protein had been reduced by up to 96 per cent by day 28 following treatment, with no serious adverse side effects.

Speaking to the Donegal News, Mr Green said he jumped at the chance to take part in the CRISPR trial when it was launched by Intellia Therapeutics last autumn.

“Earlier in the year I had found out through genetic testing that I was a carrier of the ‘Donegal Amy’ gene mutation, ThrAlA60, which can cause the full blown disease. Following a screening process at the Royal Free Hospital and Richmond Pharmacy, London, I received my CRISPR drug infusion in January.
“As the third person in the world to receive the first in human gene editing drug I was very aware of the privileged position I was in.  A potential cure for ‘Donegal Amy’ was on the horizon. Since January my TTR level, the protein which can cause the disease, has more than halved which is a great result as the trial started off on a low dose.”

He was part of the first cohort of the trail and received the lowest dose of the drug. The dosage was then upped for the second cohort.  As the trial progresses, patients will be given higher doses with the hope that it will drive levels of the toxic protein even lower.

“I am delighted Intellia are committed to giving me a full dose of the drug,” he said. “The optimum dose should achieve an even greater reduction in my TTR, close to a complete knock down to under 5 per cent. Meanwhile, I’m optimistic that the reduction already achieved will be enough to keep my amyloid stable.

“The publication of the CRISPR report in the New England Medical Journal on Saturday on the efficacy and safety of the trial made it a very good day for hAttr Amyloidosis patients worldwide. There is such great hope that this will become a disease of the past.”

The medical breakthrough is not only being hailed a major milestone for sufferers of ‘Donegal Amy’ but it could also pave the way for a revolution in the treatment of genetic disorders.

65-year-old Patrick Doherty from Gaoth Dobhair became the fifth person to receive the treatment. He was diagnosed with the disease at the start of the year but knew he might have amyloidosis because his father and other relations had died from the condition. He was referred to Professor Julian Gillmore at the National Amyloidosis Centre in London after noticing he would often become breathless and had started feeling numbness in his hands and feet.

“It’s in my family. I’ve always known that but perhaps I haven’t wanted to think too much about it. I do a lot of hill walking and noticed that I started getting a bit breathless, even when I just climbed to the top of the stairs,” said Mr Doherty.
“But since being involved in the trial I have noticed a difference. I don’t have as much numbness in my hands and feet that I used to get and I can go hill-walking with less of a problem.”

He is hoping that CRISPR has stopped or at least greatly reduced the production of the protein which will give his body a chance to try to deal with removal of existing build up around the walls of the heart and other areas.

“I had read a lot about CRISPR so when Julian mentioned the trial to me, I asked to be put forward as a volunteer. It’s for my benefit but also for the benefit of so many other people who have this condition,” he added.

Mr Doherty has also received a lot of advice and support from the ATTR Amyloidosis Ireland Support Group which does tremendous work on behalf of amyloidosis patients and families. The support group was set up last year and has expanded with members worldwide.
Anyone who would like to reach out to the group can log on to their Facebook Page ‘ATTR Amyloidosis Ireland Support Group’. Their goal is to raise awareness, advocate for a speedy diagnosis and access the best treatments available and to offer support to anyone who needs it.