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Parkinson’s drug shown to slow ALS progression in clinical trial



An early clinical trial has shown that the Parkinson’s drug ropinirole is safe to use in patients with the fatal motor neurone disease amyotrophic lateral sclerosis, and delayed disease progression by an average of 27.9 weeks.

ALS causes people to gradually lose control of their muscles and while the disease can strike at any time of life, symptoms most commonly develop between the ages of 55 and 75. Men are more likely to develop ALS than women.

There is currently no cure for ALS – which is also known as Lou Gehrig’s disease – with available treatments focussing on reducing symptoms and providing supportive care.

Researchers at Keio University School of Medicine in Japan have reported their findings in the journal Cell Stem Cell.

Senior author and physiologist Hideyuki Okano of the Keio University School of Medicine in Tokyo, said: “ALS is totally incurable, and it’s a very difficult disease to treat.

“We previously identified ropinirole as a potential anti-ALS drug in vitro by iPSC (Induced pluripotent stem cells) drug discovery, and with this trial, we have shown that it is safe to use in ALS patients and that it potentially has some therapeutic effect, but to confirm its effectiveness we need more studies, and we are now planning a phase 3 trial for the near future.”

To test ropinirole’s safety and effectiveness in sufferers with sporadic (non-familial) ALS, the team recruited 20 patients receiving care at Keio University Hospital. None of the patients carried genes predisposing them to the disease, and, on average, they had been living with ALS for 20 months.

The trial was double blinded for the first 24 weeks, meaning that the patients and doctors did not know who was receiving ropinirole and who was being given a placebo.

Then, for the following 24 weeks, all patients who wished to continue were knowingly administered ropinirole.

Many patients dropped out along the way – partially due to the Covid-19 pandemic. This meant only seven out of 13 ropinirole-treated and one out of seven placebo-followed-by-ropinirole-treated patients were monitored for the full year.

However, no patients dropped out due to safety reasons.

To determine whether the drug was effective at slowing the progression of ALS, the team monitored a variety of different measures throughout the trial and for four weeks after treatment finished.

These included changes in the patients’ self-reported physical activity and ability to eat and drink independently, and data from wearable devices and physician-measured changes in mobility, muscle strength, and lung function.

First author Satoru Morimoto, a neurologist at the Keio University School of Medicine, said: “We found that ropinirole is safe and tolerable for ALS patients and shows therapeutic promise at helping them sustain daily activity and muscle strength.”

Patients who received ropinirole during both phases of the trial were more physically active than patients in the placebo group. They also showed slower rates of decline in mobility, muscle strength, and lung function, and they were more likely to survive.

The benefits of ropinirole relative to the placebo became increasingly pronounced as the trial progressed.

However, placebo group patients who began taking ropinirole halfway through the trial did not experience these improvements. The researchers said it suggests that ropinirole treatment may only be useful if it’s started earlier and administered over a longer duration.

Dr Morimoto said: “We found a very striking correlation between a patient’s clinical response and the response of their motor neurons in vitro. Patients whose motor neurons responded robustly to ropinirole in vitro had a much slower clinical disease progression with ropinirole treatment, while suboptimal responders showed much more rapid disease progression despite taking ropinirole.”

It’s unclear why some patients are more responsive to ropinirole than others, but the researchers think this is probably due to genetic differences it’s hoped will be pinpointed in future  studies.

The researchers findings have met with a mixed response from neurological experts and others working in the field of motor neurone disease.

Michael Swash, professor of Neurology at Barts and the London School of Medicine in the UK, said the Keio report was of interest. “There has long been an effort to find an ‘off the shelf medication’ applicable to ALS management. Ropinirole may be one such drug.

“But there needs to be a clearer understanding of its mechanism of action in order to apply such knowledge more widely. In addition, a larger study is required to understand who might benefit and what might be the limits of practical therapy in using ropinirole in ALS.

“More data on possible unwanted effects are also required. There are interesting parallels in proteinaceous accumulation in the neuronal cytosol between PD and ALS that should be explored.”

Dr Brian Dickie, director of research at the MND (Motor Neurone Disease) Association, added:Whilst these results may be of some interest to the research community, the clinical trial is far too small and the findings too preliminary to draw any valid conclusions.”


Tai chi outperforms conventional exercise for seniors



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



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



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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