Living to a ripe old age is one thing. Enjoying a healthy, ripe old age is the challenge. Biotech veteran Dr Eric Leire aims to slow ageing by design, as he explains to Karen Southern.
The quest for immortality (or at least eternal youth) is an ancient concept – and nothing has made us question our own mortality more than the events of the last 18 months. But, to quote Freddie Mercury’s swansong, ‘Who wants to Live Forever? if it means enduring crippling age-related illnesses in later life.
The problem of ageing populations, especially in developed nations, has brought longevity acutely to the fore. According to OECD, health expenditure will rise from 8.8% of GDP in 2015 to 10.2% by 2030, with demographic pressures driving a quarter of this increase. For the US it has been estimated slowing aging and increasing healthy life expectancy by between one and two years is worth between $7 trillion and $38 trillion.
Dr Leire has made health span, not life span, the main focus of his work (although he admits better life expectancy would be the cherry on the cake). He is the founder and CEO of British-based pre-clinical biotech company Genflow, which is looking at ways to slow the ageing process through transformative gene therapy.
The company is working on a variant of the Sirtuin 6 (SIRT6) gene, found in centenarians, to develop a product which will repair DNA damage, boost genes and extend individual health spans by up to 25%. Clinical trials will be carried out within the next few years, and, subject to regulatory approval and successful patient outcomes, the product could be ‘on the shelf’ within a decade.
Dr. Leire has an accomplished career in scientific research and development spanning 40 years. Having held positions at Pfizer, Schering Plough and Pharmacia, he went on to be CEO at several biotechnology companies, including APT Therapeutics and Paringenix. Today he serves on the board of Immunethep, BSIM and Inhatarget. He has invented several medical patents and spent time as a research associate at the Harvard AIDS Institute. He has specialised in gene therapy for 15 years.
In a breakaway from conventional medical thinking, Dr Leire regards ageing as a disease rather than the inevitable consequence of accumulated years. As he explains: ‘Ageing is plastic, we can slow it, and reverse it.
“I believe it is unethical to view ageing as a biological process that we can’t act upon. For example, if you go to a cardiologist, you don’t expect him to say ‘You have high cholesterol or blood pressure, but we won’t treat it as a disease’.
“Yet if you tell your GP, ‘I keep losing my keys, I can’t see too well, I can’t run so fast any more,’ it’s perfectly acceptable for them to say ‘It’s just ageing, there’s nothing you can do!’
Dr Leire hopes this mindset will change, now that the biology and the nine driving factors of ageing – as identified in a 2012 study by Carlos Lopez – are better understood. “Age will then become a risk factor to treat, much like, say, statins are used to treat high cholesterol.
“Lots of companies have been set up to tackle just one of the drivers of ageing. But if you only fix 1/9th of the problem, the impact will be modest at best. We seek to tackle at least half the drivers, extend health span by delaying the diseases of old age, and also prevent loss of muscle mass, weakened immune systems, and the decline of cognitive functions.”
DNA damage is identified as the most upstream, common factor for poor ageing. Dr Leire acknowledges the role of diet and fasting in ageing well, but says the key to healthy longevity ultimately lies in DNA repair. “You only have to look at Jeanne Calment, the world’s oldest documented person. She lived to be over 122, but loved her wine and cigarettes. The key to her longevity lay in her genetic make-up. So, we need to find the genetic drivers that impact the hallmarks of ageing.
“DNA breaks easily, and constantly. It becomes a vicious circle for the genetic system, which gets overwhelmed.
“To counter this, we are currently doing trials with enhanced AAVs (adeno-associated viruses), which are easy to administer and cost-effective. We will look next at working with patients with accelerated ageing disease, (subject to regulatory acceptance). Our treatment will involve IV infusions of AAVs that can express SIRT6 into specific cells, to slow down these patients’ symptoms, such as cataracts and diabetes, and repair DNA damage.”
Gene therapy has made huge progress in the last five years. In fact, five years ago, Genflow’s work would not have been possible because the tools for the work were not available. In parallel, huge strides have been made in understanding the process of ageing. But up until very recently, the cost of therapy was hugely prohibitive.
Dr Leire explained: “Longevity gene therapy originated in California, as a very high cost treatment for Silicon Valley types.
“This is the opposite of what we want. We don’t want to give 30 extra years complete with cancers, Alzheimer’s and such like. We want to prevent the slow decay of biology that comes with age in a cost-effective, safe, ethical and user-friendly way.”
The company’s pre-clinical studies have already yielded promising results, by expressing the DNA of the Centenarian Variant of the Sirtuin 6 gene using the vector for GF-1002, which establishes that it is possible to deliver extra copies of the Variant into cells. The Centenarian Variant has also already been shown to have improved capabilities to repair DNA damage both by homologous recombination and non-homologous end-joining.
Ultimately, the company hopes their therapies could act upstream on several drivers of ageing. Trials have already proven to increase lifespan in mice by up to 30 per cent.
Dr Leire added: “Our treatments are preventative, rather than a cure. We would look to start treating people in their 50s, as age-related diseases tend to start in the 60s.
“It’s envisaged our products would be off the shelf, and patient-friendly, topically administered to the skin or injected via IV. Treatment wouldn’t need to be regular, perhaps every one or two years, at a cost of perhaps £10-£15,000.
To date, research has primarily centred on the USA, where billionaires such as Jeff Bezos and PayPal founder Peter Thiel have invested heavily in biotech research. While this investment has spurred the proliferation of firms in the longevity space across the Atlantic, in Europe a leader is yet to emerge. Genflow, based in the UK with research facilities on the continent, aims to fill this gap.
“Dr Leire explained: “My treatments aren’t aimed at the super-rich in the way they are being developed in the USA – they aren’t meant to bring back youth. We want to create therapeutic interventions, with all the ensuing benefits for the economy and society at large.”
To this end, Genflow has settled in London, “where investors are better quality”, close to the world-class genetics therapy hub of Cambridge and Oxford.
“There’s a huge appetite for biotechs right now,” Dr Leire concluded, “and Genflow hopes to become the market leader for longevity tech in Europe.”
Visit genflowbio.com for more information.