Paddy Doherty is from Gweedore, Donegal and has hereditary amyloidosis T60a otherwise known as “Donegal Amy”.
The breathlessness Paddy experienced on a hillside walk in the autumn of 2020 wasn’t his first sign of heart trouble, but it was the one that finally got him to go to the doctor.
“I am a great example of doing the manly thing, trying to ignore health problems and not wanting to seek medical advice. But, the degree of breathlessness left me in no doubt that there was something seriously wrong with me. Little did I know that just a couple of months later, I’d be urgently booking a flight to London,” he says.
By February 2021, Paddy found himself in the office of Professor Julian Gillmore at the National Amyloidosis Centre.
After testing, Paddy received the devastating diagnosis that he had hereditary amyloidosis. He says, “It meant clumps of proteins were slowly clogging up my nerves and heart, and after years of pain and inevitable progression, it would kill me.”
“Of course my next question was what could be done about it?”
Paddy knew that novel gene-silencing drugs were accessible in the UK, but not in the Republic of Ireland.
However, there was a golden glimmer of good news. Professor Gillmore offered Paddy the chance to take part in an early stage clinical trial using CRISPR cas9, a groundbreaking genome editing therapy with the potential to cure his hereditary amyloidosis in a single dose.
“The more I looked into it, the more impressed I was with the technology. It’s a ‘one-hit wonder’ involving a two-hour process, and that’s it for the rest of your life,” Paddy says.
“I love the two women that got the Nobel,” he says, referring to the Nobel Prize in Chemistry 2020 awarded to Emmanuelle Charpentier and Jennifer Doudna, the scientists behind CRISPR cas9 technology.
Paddy became the fifth person in the world to receive a CRISPR infusion.
“I had no side effects and left the trial facility after two days,” Paddy says. “The walk that I felt breathless on is a steep mountain walk through a forest. I’m doing that every Sunday now.”
Paddy hopes future Donegal Amy patients will benefit from CRISPR as much as he has. “When the trial is over, I hope CRISPR is available and affordable for all amyloidosis patients,” he says. “If a pharmaceutical company can mass-produce something like that and sell it at a good price, it would be a godsend.”
Paddy continues, “Professor Gillmore, who has been working with amyloidosis patients for over twenty-five years, told me it’s been ‘amazingly exciting’ to see the CRISPR trial results and be able to treat people like me, who otherwise wouldn’t have received adequate care. Although protein has already built up in patients like me who have symptoms, we hope that by dramatically cutting down on new buildup, the body will be able to clear out what has already accumulated.
Professor Gillmore said he has seen many families like mine ‘decimated’ by the disorder and that until maybe five years ago, there was nothing we could do to alter the natural history of the condition. That has now changed with new treatments such as gene-stabilisers, gene-silencers, and now gene-editing CRISPR if the clinical trials prove successful.”
Paddy is excited to be a part of the CRISPR story. The revolutionary gene-editing offers the possibility that his relatives and others won’t have to live with the disease.
“It’s a lonely place to receive a diagnosis like this. My first thought was for my two daughters. You don’t think about yourself at all,” explains Paddy.
Paddy’s daughters had genetic testing. Thankfully, neither carries the gene for hereditary amyloidosis. “That was such an enormous relief,” says Paddy, “and to know that the faulty gene ends with me.”
“It’s great news that Patisiran is now prescribable by a cardiologist or neurologist in the Republic of Ireland since 1st October 2021. Tafamadis has recently been approved and Inotersen may be in the pipeline, so Irish patients will have options to pursue the best treatment for them,” Paddy says.