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Genflow Biosciences: “Age is a risk factor that can be managed”

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Genflow Biosciences is a UK-based biotech company working to deliver therapeutics that slow or halt the ageing process in humans and dogs.

In January, Genflow became the first-ever longevity company to be listed on the London Stock Exchange.

The company is preparing to trials its candidate GF-1002 in patients with Werner syndrome. It is also collaborating with the University of Rochester’s Aging Research Center to assess the potential of SIRT6 gene therapy in reversing the ageing process in liver tissue.

Age Tech World sat down with CEO Dr Eric Leire to learn more about the longevity industry and Genflow’s ambitious plans for the future.

Hi Eric. Please could you start by introducing Genflow

Genflow is the first pure play longevity company to be listed in Europe and one of the few longevity-focused companies.

In the US, longevity is becoming mainstream, both in terms of clinical research and investment. Companies like Unity have huge market cap.

What we want to be the longevity reference company for Europe.

Our science focuses on SIRT6, and more specifically, a variant of the SIRT6 gene that’s linked with the control of ageing.

So when you talk about longevity, is it about living longer or living a better quality of life while you’re alive? Or a combination of both?

It’s a combination, but the main objective is not to live longer, it’s kind of a byproduct. Our real objective is to have the last 10-20 years of your life be as comfortable as possible.

To not only delay age-related diseases like type two diabetes, cardiovascular disease and cancer, but also delay the decline we observe with ageing.

Things like cognitive problems with memory. People tend to forget things more often as they get older.

Their muscle mass decreases too, which is a huge issue because that impacts your ability to move in the world. You lose those social connections.

There’s absolutely no reason now to have the last 10 years of your life miserable. We have to change the mindset that we should just accept it.

Age is a risk factor that can be managed.

We can act on the drivers of ageing, we understand the biology of ageing, and we can improve the way we age. It’s imperative on a societal level that we address this.

Dr Eric Leire

We’ve been raised with this idea that there’s a few old people at the top of the pyramid supported by a large amount of young people.

But for the first time, in human history, this pyramid does not exist. We now have more people aged over 60, than under five.

It’s impossible to have a small number of young people supporting a large mass of people who are getting sick, who are not contributing to society.

It’s not sustainable, economically or socially. So we have to do something. And we have the tools to do something. It’s very exciting to be in the longevity sector.

Human has always longed for a ‘foundation of youth.’ What developments in recent years have made living longer, better lives a realistic goal?

The main obstacle in the past was regulation.

You need to have approval from the likes of the FDA and the MHRA. Right now, these agencies are not considering ageing as a risk factor, which is ridiculous to me.

Covid has given us a fantastic illustration that ageing is a risk factor for infectious disease and that an older person’s immune system does not respond as well as that of a young person.

It’s obvious now, it’s becoming a mainstream concept. People don’t develop type two diabetes in their 20s, strokes and cancer are rare. Age plays a major role.

The fact now that the agencies are moving to accepting ageing as a risk factor is a major driver. And when this will happen, that will be a major change, because science is advancing extremely fast.

It’s started with repurposing. A few guys proposed taking things like vitamins and green tea. Forget that. It’s of marginal benefit.

Then there was some repurposing of drugs like metformin. Through this research, we’ve seen the first indication that the FDA will consider ageing as a risk factor. And that could lead to the approval of metformin to be an agent against ageing.

There are also now a lot of companies that want to act on the drivers of ageing. Unity is the big one.

We have a pretty good understanding of what drives ageing. We understand that we can reprogram cells and that cells lose their programming over time.

Ageing is plastic, we can reverse it. It doesn’t flow in one direction. Every week, there’s a new paper coming in and we understand more.

Where does gene therapy fit in?

If you use metformin, if you do intermittent fasting, if you lower your caloric intake, you can live a little bit longer.

But how well or badly we age is genetically determined. A human being can live until 126 but no more.

If we want to have a significant impact, it’s at the genetic level. So we need to boost our genetic equipment to deal better with the repair of DNA and reprogramming of cells.

Gene therapy and gene delivery are now booming.

The two AAV drugs that were approved [Zolgensma and Luxturna] were million-dollar drugs. Now we have the means to develop AAVs that are less immunogenic with a better safety profile.

We can modify the capsid [protein shell] of AAVs, we can use exosome to protect them from the being seen by the immune system. So we have multiple tools and we can also decrease the lab scale cost of AAVs, so they are no longer a million dollars.

That’s very important because when people think ageing, they think it will only be Jeff Bezos and his friends who are jogging and doing the marathons and 150 while the rest of us die horribly at 90. That’s not the case.

We can have now affordable, ethical gene therapy that is not passed on to your children. The combination of the advanced gene therapy and a deeper understanding of the process of ageing allows us to provide some very nice solutions.

So how are you applying this now with your lead compound GF 1002?

Werner syndrome is a disease of accelerating ageing. It’s very important for us to stay as close as possible to ageing tenants.

When you’re a serious company that wants to get a drug approved, you have to go to the MHRA or FDA and address an indication that they regulate.

We went with progeria because it’s a rare disease which gives us the opportunity to seek Orphan Drug Designation (ODD). They’re working on the ODD right now.

That allows us to have multiple interactions with the agency. This is extremely important because, as gene therapy, early interaction with the agencies is an extremely important factor of success.

Longevity is now major, mainstream research. It’s not something on the side, but it’s mostly biotech companies. It’s too risky for pharma.

I come from an immunooncology background. For the first 10 years, people said it would never work. Pharma was not interested. And then the last 10 years were fantastic and now we’re seeing these acquisitions at crazy prices.

The UK Government is very concerned about the financial and social burden a large number of people old people will put on the young. So the MHRA will be feeling the pressure.

As soon as regulators shift to accepting ageing an indication, there will be major acquisition waves from the pharma industry.

Everybody without exception will age. So it’s the ultimate market.

We’ve seen movement from the FDA, so we know it’s coming. The only question is, will it be one year, two years, three years? Which agency will be first?

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Study shows clear link between CTE and dementia risk

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A new study says CTE should be recognised as a cause of dementia, with those in the most advanced stages facing a 4.5-fold higher lifetime risk.

Chronic traumatic encephalopathy (CTE) is a degenerative brain condition seen in some athletes.

Linked to repeated head impacts, it can cause memory loss, mood changes, poor coordination and suicidal thoughts. Diagnosis is only possible after death.

People with the most advanced CTE were 4.5 times more likely to develop dementia during life than people without CTE, researchers found.

Many former NHL and NFL players have been posthumously diagnosed with CTE, including Junior Seau, Frank Gifford and Ken Stabler.

The study from researchers at the Boston University CTE Center provides what the centre describes as the clearest evidence yet linking CTE to dementia risk.

The centre says these findings indicate CTE should be known as a cause of dementia.

“This study provides evidence of a robust association between CTE and dementia as well as cognitive symptoms, supporting our suspicions of CTE being a possible cause of dementia,” said Dr Michael Alosco, an associate professor of neurology and co-director of clinical research at the BU CTE Center.

“Establishing that cognitive symptoms and dementia are outcomes of CTE moves us closer to being able to accurately detect and diagnose CTE during life, which is urgently needed.”

Researchers studied brain tissue from more than 600 donors, the majority men.

The donors, primarily contact sport athletes, had known exposure to repetitive head impacts, but none had Alzheimer’s disease, Lewy body disease or frontotemporal lobar degeneration.

They found that 366 male donors had CTE. After examining the donor brains, they calculated the odds of developing dementia across CTE stages I to IV.

Donors with stages III and IV had the worst cognitive and functional symptoms, regardless of age or history of substance use treatment.

Lower stages were not associated with dementia, cognitive impairment or functional decline.

The team also found no link between less severe CTE and changes in mood or thinking, suggesting observed changes may stem from other effects of repetitive head impacts or unrelated medical or environmental factors.

“Understanding which brain changes drive cognitive decline is essential,” said Dr Richard Hodes, director of the National Institute of Health’s National Institute on Aging.

“This study shows that only severe CTE has a clear link to dementia, which provides an important distinction for researchers, healthcare providers and families.”

The study also found that dementia due to CTE is often misdiagnosed as Alzheimer’s disease.

Both conditions are marked by abnormal tau proteins that build up in brain cells and affect blood vessels, although the tau differs in each disease.

Of donors with CTE who had received a dementia diagnosis during life, 40 per cent were told they had Alzheimer’s disease but showed no evidence of it at autopsy.

A further 38 per cent of families were told the cause of dementia was unknown or could not be specified.

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ATW’s research round-up: new Alzheimer trigger identified, UK university targets longevity. fibre not protein?…and more

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A UK university will become one of the first in the country to make improving the health and well-being of the elderly one of its six ‘mission-led’ research priorities.

Bournemouth University’s choice to focus on pensioners is partly the result of the Labour Government’s wish for universities to specialise, whilst also reflecting the area’s demographics – the south-coast city has one of the one of the oldest populations in the world.

“Our demographics are much older than other places – about 10 years older on average compared to the rest of the UK,” explained Tom Wainwright, professor of orthopaedics at Bournemouth.

Vary your exercise

The university’s Orthopaedic Research Institute is already heavily involved in work with the surrounding area and its recently published study, in The Lancet, showed that over-65s with osteoarthritis who undertook group-based cycle classes enjoyed much better outcomes than those receiving one-to-one physiotherapy.

Research published in leading British doctors’ publication the BMJ Journal, which tracked 100,000 people over the last 30 years, has shown that mixed exercise routines can have a significant impact on overall health and longevity.

The study tracked the cohorts exercise habits over three decades and found that participants who engaged in the highest variety of exercises had a 19% lower risk of death, compared to those who engaged in the lowest variety.

Benefits were even bigger when looking at specific causes like heart disease, cancer, and respiratory illness, with risk reductions ranging from 13 to 41 percent.

“People naturally choose different activities over time based on their preferences and health conditions,” says Yang Hu, corresponding author and research scientist in the Harvard TH Chan Department of Nutrition.

“When deciding how to exercise, keep in mind that there may be extra health benefits to engaging in multiple types of physical activity, rather than relying on a single type alone.”

US researchers have identified over five dozen new potential blood-based metabolites which could predict a Type 2 diabetes risk, years in advance.

Key Alzheimer trigger identified

Scientists at Mass General Brigham and Albert Einstein College of Medicine, followed 23,634 participants for up to 26 years and over that time analysed 469 metabolites in blood samples, alongside additional genetic, diet and lifestyle data.

In doing so they identified 235 metabolites associated with higher or lower diabetes risk, including 67 new molecules previously unreported.

The researchers say their work supports a shift toward precision prevention strategies which are more reliable than current indicators such as BMI or family history.

Further research into the Alzheimer’s predicting APOE (apolipoprotein E) gene has left UK researchers with renewed conviction of their ability to develop preventive measures, earlier in life.

Researchers at University College London analysed nearly 470,000 people across four major studies, focusing on participants aged 60 and older with confirmed Alzheimer’s diagnoses and genetic data.

Whilst previous studies had identified the ε4 allele of APOE as the one most predictive of Alzheimer’s development the UCL researchers also highlighted how allele ε3 may also carry a significant risk

Dr Dylan Williams, the study’s lead author, explained that the APOE gene’s contribution to the prevalence of Alzheimer’s has been significantly underestimated for a long time, and that the ε3 allele has historically been misunderstood as having a neutral effect on risk.

He said: “Intervening on the APOE gene, or the molecular pathway between the gene and Alzheimer’s, could have huge potential for preventing or treating a large majority of cases.”

Fibre first

Researchers say that fibre – found in beans, lentils, chia seeds, oats, bran, and certain fruits – is emerging as the ‘new hero’ of nutrition science.

Longevity expert Dr Vassily Eliopoulos, MD, who trained at Cornell, highlights how protein has ruled diet trends for years, but says fibre is now stepping into the spotlight.

“Everyone’s chasing protein, but the next big longevity macro is fibre. And fibre might be the most under-appreciated longevity nutrient that you’re missing daily.”

Explaining why fibre plays such a crucial role, he highlights the connection between gut health and overall well-being.

“Here’s the secret, your gut microbes eat what you don’t digest. These microbes convert fibre into powerful compounds that protect the body. They turn fibre into short-chain fatty acids, which act as your body’s natural anti-inflammatory molecules,”

Dr Eliopoulos highlights how chronic inflammation is closely linked to ageing and disease and he recommends aiming for 30 to 40 grams of fibre a day.

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Assisted dying should be ‘gradually’ extended to dementia, author Ian McEwan says

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Author Ian McEwan said legalised assisted dying should be gradually extended to people with dementia.

Speaking at a public book event in London on 28 January, he criticised attempts to block the UK’s assisted dying bill, citing more than 1,000 amendments.

Supporters believe it is near impossible for it to pass the House of Lords before the end of the session in May due to alleged filibustering.

If passed, the bill would legalise assisted dying in England and Wales for adults with less than six months to live.

“I like it when some bishop says on the radio: ‘It’s the thin end of the wedge,’ and I think yes, it is the thin end of the wedge,” said McEwan, who is a patron of Dignity in Dying.

“Certain groups are missing from it, such as those with dementia. It has to be physical pain.

“My guess is that if we pushed it through with all the protections around it – of doctors and dispassionate people making judgements – we’ll look back on this and think, ‘Why did we ever let people die in agony?'”

Asked if he would add an amendment to extend assisted dying to dementia sufferers, McEwan said: “Gradually, yeah, I would. But I think it does require a lot more thought and the idea of living wills.”

“My mother used to say to me: ‘If I ever become really terrible, I’d like you to finish me off.’ But of course, that’s to commit murder as things stand. Imagine standing up in court and saying: ‘Well, she did say when we were on the beach 20 years ago…'”

McEwan spoke about dementia’s impact on his family.

His mother Rose had dementia, as well as his brother-in-law and another close family member.

“By the time my mother was well advanced and could not recognise anyone, she was dead. She was alive and dead all at once.

“It was a terrible thing. And the burden on those closest is also part of the radioactive damage of it all.”

McEwan was speaking at St Martin-in-the-Fields church in central London, as part of its Conversation series, discussing his latest book, What We Can Know, in which dementia is a major theme.

He has also written about dementia in previous novels, Lessons and Saturday.

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