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Genetic test should be new standard of care in UK for stroke patients

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People who have had the most common type of stroke should have a genetic test to find out whether they can be treated with a drug to help reduce the risk of further brain attacks, the UK’s NHS watchdog has said.

New draft guidelines published on May 19 by the National Institute for Health and Care Excellence (NICE) recommend that people who have suffered an ischaemic stroke – where a clot blocks the flow of blood and oxygen to the brain – or a transient ischaemic attack (TIA) should be offered laboratory-based genotype testing if treatment with the drug clopidogrel is being considered by clinicians.

NICE currently recommends clopidogrel can be used as an option for treating people at risk of a secondary stroke but this treatment is not suitable for those with certain variations in a gene called CYP2C19 because they cannot convert the drug to the active form.

The genotype test would be used to find out who has these variants so they can be treated with an alternative drug = potentially saving thousands of lives.

If laboratory testing – estimated to cost around £139 per analysis – is not possible, NICE has said the Genomadix Cube point-of-care check at a cost of £197, which can be given at the bedside, can be used instead.

There are around 100,000 strokes every year in the UK, of which approximately43,000 are recurrent. Each year, 46,000 people in the UK have a TIA for the first time – a warning that they are at risk of stroke.

A stroke can occur in anyone of any age. but the chance of having one about doubles every 10 years after reaching 55. The majority of strokes occur in people who are 65 or older.

Clopidogrel – which also goes under the brand names Grepid and Plavix – is the standard anti-clotting medication given to patients.

But at present no testing takes place to find out who is suitable for treatment with the drug.

An estimated 32% of people in the UK have at least one of the highlighted CYP2C19 gene variants. They are more commonly found in people with an Asian family background but can be present in those of any ethnicity.

Evidence has suggested that people with these variants have around a 46% increased risk of another stroke when taking clopidogrel compared to those without them.

If the test discovers they have one of the CYP2C19 gene variants, the person will be treated with another medicine, which will be more effective at preventing future blood clots.

Around 11 million items of clopidogrel are dispensed each year at a cost of around £16 million to the NHS.

Mark Chapman, interim director of medical technology and digital evaluation, at NICE, said: “The recommendation is a step forward in ensuring people who have had a stroke receive personalised care thanks to a genetic test run after their DNA is sequenced using their blood or saliva.

“Treatment with clopidogrel is effective in preventing further strokes for the majority of people who don’t have the gene variant. But until now doctors have not known who cannot be treated with clopidogrel until after they’ve had a second stroke or TIA and that could be too late.

“If the CYP2C19 variants are found, other treatment options can be used. This test ensures we’re getting the best care to people quickly, while at the same time ensuring value for money for the taxpayer.”

A consultation has begun on the draft recommendations and consultees can have their say via nice.org.uk until Wednesday June 8, 2023.

Juliet Bouverie, Chief Executive of the UK-based Stroke Association, has welcomed the NICE announcement. She said: “Stroke devastates lives and leaves people with life-long disability. We know that many stroke survivors spend the rest of their lives fearing another stroke, so it’s great to see that more people could be given appropriate help to significantly cut their risk of recurrent stroke.

“Anything we can do to prevent the misery that stroke can cause is ultimately good news. Getting on the right medication and taking it as advised can really go far to prevent further strokes.”

A team at NHS Tayside in Scotland led by stroke specialist Dr Alex Doney at Ninewells Hospital in Dundee, has already been pioneering routine gene testing for clopidogrelin in brain attack patients. It has been estimated the test, developed by East of Scotland Regional Genetic Laboratory, will lead to improved outcomes for about 400 patients with heart disease and 600 stroke patients each year.

One of the first patients in Tayside to be managed on the new stroke pathway has been 67-year-old Ian Anderson from Perth. He has previously said: “I felt privileged to be one of the first patients in Tayside to be involved in this new approach. It really is a step into the future and one that will benefit patients in the coming months and years.

“It is quite amazing that a simple blood test can show if my medication is working as effectively as possible and it is reassuring that my medication can be tailored more precisely to me.”

Clinicians believe this is just the tip of the iceberg and other conditions could soon benefit from the same precision prescribing, making routinely given medicines safer and more effective for individual patients.

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Tai chi outperforms conventional exercise for seniors

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New findings from 12 studies involving 2,901 participants have demonstrated that tai chi outperforms conventional exercise in improving mobility and balance in seniors.

While tai chi is understood to be beneficial for functional mobility and balance in older adults, such benefits are not well understood due to large variance in research study protocols and observations.

This new review and analysis has now shown that tai chi can induce greater improvement in functional mobility and balance in relatively healthy older adults compared to conventional exercise.

The findings showed the following performance results:

  • The time to complete 50-foot walking was 1.84 seconds faster. 
  • The time to maintain a one-leg stance was 6 seconds longer when eyes were open and 1.65 seconds longer when eyes were closed. 
  • Individuals improved their timed-up-and-go test performance by 0.18 points, indicating quicker standing, walking, and sitting.
  • Individuals taking the functional reach test showed significant improvement with a standardised mean difference of 0.7, suggesting a noteworthy positive impact on the ability to reach and perform daily activities.

Secondary analyses revealed that the use of tai chi with relatively short duration of less than 20 weeks, low total time of less than 24 total hours, and/or focusing on the Yang-style of this ancient form of Chinese martial arts were particularly beneficial for functional mobility and balance as compared to conventional exercise.

“This systematic literature review and meta-analysis are exciting because they provide strong evidence that tai chi is a more efficient strategy to improve functional mobility and balance in relatively healthy older adults, as compared to conventional exercise,” said Brad Manor, Ph.D., director of the Mobility and Falls Program at Hebrew SeniorLife’s Hinda and Arthur Marcus Institute for Aging Research, and associate professor of medicine, Harvard Medical School and Beth Israel Deaconess Medical Center.

“This research suggests that tai chi should be carefully considered in future studies and routines of rehabilitative programs for balance and mobility in older adults,” said Bao Dapeng, professor at Beijing Sport University.

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New standards for biomarkers of ageing

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A paper has put forward a new framework for standardising the development and validation of biomarkers of ageing to better predict longevity and quality of life.

Led by Harvard researchers, the team has zeroed in on biomarkers of ageing using omic data from population-based studies. 

The team included ageing and longevity expert Alex Zhavoronkov, PhD, founder and CEO of AI-driven drug discovery company Insilico Medicine, and the findings appeared in Nature Medicine

Ageing is associated with a number of biological changes including increased molecular and cellular damage, however, researchers do not yet have a standardised means to evaluate and validate biomarkers related to ageing. 

In order to create those standards as well as actionable clinical tools, the team analysed population-based cohort studies built on omic data (data related to biological molecules which can include proteomics, transcriptomics, genomics, and epigenomics) of blood-based biomarkers of ageing. The researchers then compared the predictive strength of different biomarkers, including study design and data collection approaches, and looked at how these biomarkers presented in different populations. 

In order to better assess the impact of ageing using biomarkers, the researchers found that clinicians needed to expand their focus to consider not only mortality as an outcome, but also how biomarkers of aging are associated with numerous other health outcomes, including functional decline, frailty, chronic disease, and disability. They also call for the standardisation of omic data to improve reliability. 

“Omics and biomarkers harmonisation efforts, such as the Biolearn project, are instrumental in validation of biomarkers of aging” said co-first author Mahdi Moqri, PhD, of the Division of Genetics. 

Biolearn is an open-source project for biomarkers of aging and is helping to harmonise existing ageing biomarkers, unify public datasets, and provide computational methodologies.

The team also emphasised the importance of continued collaborations among research groups on “large-scale, longitudinal studies that can track long-term physiological changes and responses to therapeutics in diverse populations”, and that further work is required to understand how implementation of biomarker evaluation in clinical trials might improve patient quality of life and survival.

“If we hope to have clinical trials for interventions that extend healthy lifespan in humans, we need reliable, validated biomarkers of ageing,” said co-first author Jesse Poganik, PhD, of the Division of Genetics. 

“We hope that our framework will help prioritise the most promising biomarkers and provide health care providers with clinically valuable and actionable tools.”

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Healthy aging research to receive $115 million

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Global non-profit Hevolution Foundation has announced $115 million in funding that makes up 49 new awards under its Geroscience Research Opportunities (HF-GRO) programme.  

As part of Hevolution’s mission to catalyse the healthspan scientific ecosystem and drive transformative breakthroughs in healthy aging, HF-GRO is funding promising pre-clinical research in aging biology and geroscience. 

Through this first wave of HF-GRO awards, Hevolution will invest up to $115 million in this first cohort of 49 selected projects over the next five years. Its second call for proposals under HF-GRO will be announced later this year, offering an additional $115 million to address the significant funding gaps in aging research.  

Dr. Felipe Sierra, Hevolution’s Chief Scientific Officer stated: “These 49 important research projects represent a significant step forward in deepening our understanding of healthy aging. Hevolution’s prime objective is to mobilise greater investment around uncovering the foundational mechanisms behind biological aging. 

“We are steadfast in our belief that by examining the root causes of aging, rather than solely focusing on its associated diseases, we can usher in a brighter future for humanity.” 

HF-GRO awardees include researchers at prestigious institutions across the United States, Canada, and Europe, including the U.S. National Institute on Aging, Brigham and Women’s Hospital, the Buck Institute, the Mayo Clinic, New York University, and the University of California San Francisco, among many others. 

The American Federation for Aging Research is providing programmatic support for the HF-GRO program, with grantees selected through a rigorous two-stage peer-review process involving 100 experts in aging biology and geroscience. 

Dr Berenice Benayoun, an HF-GRO grant recipient at the University of Southern California, stated: “I am extremely honored and excited that Hevolution selected our project for funding. This is a project close to my heart, which aims at understanding why and how the female and male innate immune aging differs. 

“This funding will support us as we start laying the foundation for a lasting improvement of women’s health throughout aging.” 

To date, Hevolution has committed approximately $250 million to transform the healthy aging sector, including the $40 million for specialised research and development in healthspan science recently announced at Hevolution’s Global Healthspan Summit. 

Hevolution is ramping up its investments to enable healthier aging for all and is now the second largest funder of aging biology research worldwide.  

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