enzngin Fifth Estate

Kiwi patients with a painful and debilitating inherited illness say gene-editing therapy has changed their lives.

Kiwi patients with a painful and debilitating inherited illness say gene-editing therapy has changed their lives and completely relieved their symptoms.
 
The group of seven patients who participated in a clinical trial have hereditary angioedema, meaning they formerly experienced unpredictable, sometimes frequent and potentially lethal attacks of swelling.
 
They were treated in late 2021 and early 2022 in the New Zealand Clinical Research facility in Auckland, as part of a first-in-human clinical trial of the CRISPR-Cas9 gene-editing therapy.
 
“It looks as if the single-dose treatment will provide a permanent cure for my hereditary angioedema patients’ very disabling symptoms,” says principal investigator Honorary Senior Lecturer Dr Hilary Longhurst. “Plus, of course, there is huge potential for development of similar CRISPR-Cas9 treatments for other genetic disorders.”
 
People with hereditary angioedema find the attacks of swelling impact on their ability to take up normal opportunities in work and life.
 
The attacks may occur several times a week or a few times a year.
 
Over a lifetime, the disorder is associated with significant anxiety and depression.
 
The patients who participated in the trial are reporting that the therapy has been “life-changing”, says Dr Longhurst.
 
“Many of the patients have had family members who have died and they are absolutely terrified,” Dr Longhurst says. “They are frightened both of the pain of abdominal attacks, which is comparable to that of heart attacks and childbirth, but also the fact their airways might swell up and they might suffocate.”
 
Globally, it is estimated one in 50,000 people have the hereditary angioedema, which means it is likely 100 New Zealanders have the condition. However, because it is rare, it is often not correctly diagnosed. So far only around 60 Kiwi patients have been identified.
 
Patients have an inherited deficiency of the C1 inhibitor protein, which controls a biochemical pathway linked to inflammation. Without sufficient C1 inhibitor, the body gets a build-up of a protein fragment (peptide) called bradykinin, which stimulates swelling.
 
The therapy is delivered via a lipid nanoparticle, or miniscule ball of fat, containing the CRISPR-Cas9 genetic material, and is infused through a vein in the patient’s arm over two to four hours.
 
“This ball of lipid targets the treatment into the liver, and then the CRISPR guides the Cas9 onto exactly the gene that is causing the problem,” Dr Longhurst says.
 
The gene, KLKB1, produces a protein precursor to bradykinin, called kallikrein.
 
“The CAS9 acts as a molecular scissor to cut the KLKB1 gene. The body heals the break in the KLKB1 gene, but in doing this it sows additional bits of genetic material so that gene doesn't work anymore.
 
“The effect of the treatment is to silence the KLKB1 gene and to prevent overproduction of the kallikrein and bradykinin that cause the swelling.
 
“I always warn the patients that they may feel fluey on the day of the treatment but in fact the symptoms have been minimal,” Dr Longhurst says. “Some people feel a bit tired or have a headache, and one person had a bit of a temperature that lasted a few minutes. It’s been incredibly well tolerated.”
 
After a single treatment, the patients either had no more attacks of swelling or a dramatic reduction and then cessation of attacks after a few weeks.
 
“One patient, who had been experiencing frequent severe attacks, took a while to settle down, but most were immediately attack-free,” says Dr Longhurst.
 
By January 2023, ten months 14 months after the first treatment, almost all the patients have been free of attacks for between two and ten months and all patients have been able to stop their previous angioedema medications. The exception was a minor hand swelling after a sports injury, which technically classified as a potential angioedema.
 
Dr Longhurst, an Honorary Associate Professor of Medicine at the University of Auckland, presented results from the trial at a November meeting of the American College of Allergy, Asthma and Immunology, with the abstract published in the Annals of Allergy, Asthma & Allergy (November 2022). http://www.sciencedirect.com/science/article/abs/pii/S1081120622012170
 
The US company, Intellia Therapeutics, chose New Zealand for the first-in-world trial as the country had relatively little Covid-19 at the time, late 2021.
 
Since the New Zealand trial, family members of participants and patients in the Netherlands and the UK have received the same treatment.
 
The next stage will be a randomised, double-blinded, placebo-controlled trial.

Opinion: The waning use of cash in New Zealand, paired with emerging technology, has encouraged the investigation of a central bank digital currency (CBDC), which unlike cryptocurrency, is supported by the Government and issued by a central rather than commercial banks.

In a world where cryptocurrencies and big-tech companies are aggressively infiltrating financial services, the idea of issuing a CBDC in New Zealand is, at least in part, a defensive move to protect the country’s monetary sovereignty. It may also be a protective measure against potential currency substitution challenges posed by foreign CBDCs.

China launched its central bank-issued digital currency, the e-CNY, in 2020. However, the country’s rollout of its digital yuan has been met with some concerns, including that it could be used to monitor citizens and, in time, evade international sanctions.

The People’s Bank of China began digital yuan investigations in 2014. It established the China Digital Currency Research Institute in 2016, completed research, design and system testing in 2019, launched the e-CNY (Chinese yuan) in 2020, also known as the electronic Chinese yuan or digital yuan, and has since been conducting on-the-ground trials in more than 20 cities across the country. One such trial was carried out at the 2022 Beijing Winter Olympics, where over e¥315,000 in e-yuan was reported to have been used every day.

Along with the birth of the e-CNY, the Chinese economy has witnessed a dramatic transition towards digitalisation. The majority of people already use mobile payment services such as Alipay and WeChat Pay, and in major cities like Beijing, even beggars use QR codes and mobile payment apps to accept donations. This almost total societal adoption of digital transformation speaks to the potential of the e-CNY.

However, the introduction of China’s digital currency is not simply a phenomenon in which the impacts are felt domestically. There is an increasing sentiment that as an early adopter of a central bank digital currency, the Chinese yuan has an advantage in competing with the US dollar as the world’s main reserve currency. Many in the international community also wonder whether the rollout of the e-CNY will reshape the world’s currency landscape and impact bilateral, regional and multilateral economic and business interactions.

In response to concerns about the e-CNY, Chinese financial officials have repeatedly said that efforts to create a digital yuan are aimed at serving domestic retail demands. Moreover, they emphasise that the e-CNY changes only the yuan’s form and ways of usage, not its actual value or impact on the international financial market and system.

In addressing growing public curiosity and enthusiasm within China about the yuan, as an international currency, Chinese finance professionals, scholars, and commentators state that the e-CNY is a helpful but “insufficient provision” for the yuan’s global adoption and usage.

They also emphasise that history indicates that the internationalisation of a country’s currency often lags behind the growth of its economic power. Citing the International Monetary Fund’s findings that the Chinese yuan still accounts for less than 3 percent of global foreign currency reserves, they say that the journey for the yuan to become a popular global currency will be long and evolutionary.

Nonetheless, many Chinese finance professionals, researchers, and commentators hail the e-CNY system as an innovative and robust financial infrastructure. They are hopeful that when embellished with features like lower costs, higher efficiency, and “settlement upon payment”, the e-CNY will appeal to countries that are world leaders in the digital economy but furnished with a limited number of large companies with global influence. These countries usually pay special attention to opportunities for their SMEs to adapt to and benefit from new digital business models and trading patterns.

Standing out in this group, as noted in some Chinese studies, are Singapore and New Zealand, which are also highlighted as important Regional Comprehensive Economic Partnership (RCEP) participants and founding members of the world’s first digital economy partnership (DEPA).

The notion of building a financial silk road and promoting local currencies first in cross-border economic and business activities has been gaining traction in Chinese corporate circles.

Many in China’s business and research sectors give particular importance to RCEP members as most are not only on China’s Belt and Road Initiative land and maritime routes, they are also some of the world’s most important producers and consumers of bulk commodities.  

The free trade agreement has thus opened new avenues for China to work with the RCEP countries in building a united commodities market where currencies from within the region, including their digital formats, are used as the standard price and settlement mechanism. The efforts in this regard should allow the e-CNY more opportunities to help expedite the ascendance of the yuan to a regional anchor currency status for trade settlement, direct investment, loans, and aid funds.