Earlier this month a patient in New Zealand was injected with gene-editing instructions to modify a single letter of DNA responsible for producing LDL (or bad) cholesterol.
Previously tried on monkeys, which resulted in a 70 percent reduction in cholesterol levels, the volunteer is US-based biotech company Verve Therapeutic’s first human test case.
Co-founder and chief executive Sekar Kathiresan said the treatment was a milestone.
“The medicine that we’re using is called a CRISPR base editing medicine and this is the first time such a medicine has ever been administered to a human being.”
He said all going to plan a “one and done” treatment would likely be available for the average consumer in 2028 or 2029 – an outcome that would fulfil an unmet need.
“Heart attack is the leading cause of death in the world and the number one way to treat heart attack patients is to get their LDL as low as possible for as long as possible and right now, that’s being done very poorly.
“Very few patients in New Zealand and globally get their LDL well controlled and the major reason for this is because of the chronic care model. So for chronic disease like heart disease, we’re expecting patients to take daily pills for their whole life, we’re expecting them to have regular health care access and all of those things really are not happening in most of the world.”
Following the first test in New Zealand plans for a wider phase one trial with about 40 participants across New Zealand, UK and the US are also in the works, with results expected some time next year.
The Heart Group and Auckland City Hospital Cardiologist Dr Ralph Stewart said the work was “revolutionary”.
“Heart disease is the leading cause of premature death for New Zealanders.
“Pills to lower cholesterol are very effective and we know that they are beneficial. But a lot of people for one reason or another, stop taking them after a while, and they don’t necessarily make you feel better one day to the next… so over many years if you could avoid that it would be a huge advance.”
“I do think it is the future, there’s no doubt about that and at some point, we have to go into humans. I think everyone’s going to be watching these trials very closely to see how they go.” – Dr Hilary Sheppard, Auckland University
Heart Foundation medical director Gerry Devlin agreed the trial looked promising, but cautioned against touting it as a cure.
“High cholesterol is only one of the risk factors we know which can lead to heart attack and strokes so while it may impact on the burden of heart disease significantly, it won’t result in a cure.”
Auckland University Biological Sciences senior lecturer Dr Hilary Sheppard said it was an exciting time for the gene-editing field.
“I do think it is the future, there’s no doubt about that and at some point, we have to go into humans. I think everyone’s going to be watching these trials very closely to see how they go.
“The key here though is that you’re dealing with, I assume, a fully-informed consenting adult, and all the changes that are being made to their genome will not be inherited. We’re not talking about germline editing, which is inheritable. If it was I’d be completely against it.”
Verve Therapeutics’ Kathiresan said germline editing – a controversial science where inheritable genomes are edited – was what people confused for gene editing.
He said gene editing was similar to surgery in that it was a permanent change, agreed to by a fully-informed consenting adult.
“We’re editing the DNA of the person of the patient and that’s in their own body and they’re giving consent for that editing to happen … the kind of editing we’re doing is not going to involve sperm or egg or embryos, and it cannot be passed on to the offspring of the person, it really only affects that person’s own body.
Technology vs legislation
Two years ago an expert panel set up by the Royal Society Te Apārangi concluded it was time for an overhaul of New Zealand’s gene technology regulations and that there was an urgent need for wide discussion and debate about gene editing within and across all New Zealand communities.
But Sheppard said since then nothing had fundamentally changed.
“It really just becomes a bit of a political hot potato… so I think as governments come and go, nobody really wants to deal with it, because it could kill them politically and so therefore the whole field is hampered.”
She said the legislation was nonsensical at times, giving the example of her research, which involved editing genes outside of the body, being subject to approval by the Environmental Protection Authority under the Hazardous Substances and New Organisms Act, and the current trial.
“What I’m doing is arguably safer, and yet I have to go through the EPA and I’m going to have to do a whole determination to try and get my gene-edited cells – if I wanted to get them out of the research lab – into the clinic.
“And yet, we can do trials in humans, which don’t have to go through that.”
“It cannot be passed on to the offspring of the person, it really only affects that person’s own body.” – Sekar Kathiresan, Verve Therapeutics
Kathiresan said part of the reason Verve picked New Zealand as a place to undertake trials was because similar gene-editing applications had come across the regulators desk before.
Last year, US firm Intellia Therapeutics conducted a gene-editing trial seeking a fix for hereditary angioedema – a rare and potentially life-threatening condition that causes episodes of swelling in the tissues of different parts of your body.
“Because of that, we knew that the New Zealand health authorities had seen an application like the one we were going to submit and actually already had approved a similar application.
“In addition, there is a cadre of cardiologists in New Zealand who have substantial experience with this genetic disease of familial hypercholesterolemia.”
A Medsafe spokesperson said the trial gained approval following a recommendation from the Health Research Council.
It was also recently approved by the Health and Disability Ethics Committee.