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Animal drug could be repurposed to help osteoarthritis sufferers



Millions of osteoarthritis sufferers across the world could soon benefit from a pain relief drug currently used to treat joint issues in horses, cats, dogs and even racing camels.

Australian late-stage clinical development company Paradigm Biopharma is investigating injectable pentosan polysulfate sodium (iPPS) as a potential disease-modifying treatment for knee osteoarthritis (KOA).

The plant-derived, semi-synthetic drug has been used in the veterinary space for over 80 years to improve joint health and preserve cartilage integrity. It is registered for use by vets in more than 20 countries.

Until now, pentosan polysulfate sodium has only been used in humans over the age of 16 to treat blood clots and the discomfort or bladder pain associated with interstitial cystitis.

However, a number of current and former Australian Football League (AFL) players have been using Paradigm’s iPPS under a Special Access Scheme (SAS). This is a programme set up by the Therapeutic Goods Administration (TGA) for doctors to prescribe medications that are not listed on the Australian Register of Therapeutic Goods (ARTG).

After being repurposed and provided via subcutaneous injections in various trials, Paradigm has said the drug’s capabilities are proving to be more applicable in treating osteoarthritis, caused by the breakdown of cartilage in joints.

Now the company aims to bring hope to the estimated half a billion osteoarthritis sufferers around the world – 70% of whom are affected by the degenerative joint disease in the hip or knee.

There are currently no disease-modifying osteoarthritis drugs approved for the treatment of KOA. Instead non-steroidal anti-inflammatory drugs, analgesics and glucocorticoid injections are commonly prescribed for treatment.

But each of these drugs only deal with the symptoms, leaving the underlying degenerative problems untreated.

With osteoarthritis expected to become the single greatest cause of disability globally by 2030, there is a considerable unmet medical need for a disease-modifying drug.

Paradigm, which has its head office in Melbourne, Victoria, is focused on improving patients’ health and quality of life through the development of known therapeutics to address unmet medical needs in conditions where sustained inflammation is present.

People with osteoarthritis need alternative therapeutic solutions, as the current treatments often don’t provide sufficient relief, leaving them in pain and with a reduced quality of life.

Former Geelong, Sydney Swans’ and Carlton AFL player, Greg ‘Diesel’ Williams, 59, understands only too well how knee OA can have a devastating impact on your life.

Greg, who played AFL for 14 years during the 1980s and 1990s and is a dual Brownlow Medal winner who at his peak was the then-highest-paid player in the history of the sport, suffers with severe knee OA. A one-time world class athlete, he now can’t run, and has difficulty walking.

He explained: “If you’ve got OA people really don’t understand what we’re going through. It’s so painful. It’s so sore. It’s so, so hard to put up with. And it’s about time we did something about it.”

He has tried all kinds of medication, and spoken with the best surgeons, but is still in severe pain with KOA. He added: “If I could find a solution that’s medical, not surgical, yeah, I’d be going for that 100mph.”

As yet he doesn’t want to go down the path of having a knee replacement. “I may have stopped playing, but I don’t want to stop living,” he said.

Dr Philip Bloom, a specialist sports physician with over 20 years’ experience and specialist training in treating and managing musculoskeletal injuries and diseases to maximise function, explained: “Osteoarthritis of the knee is not just an isolated pain in the knee. It has a trickle-down effect on the rest of your life, particularly in regards to losing the ability to be active, which causes obesity, more aches and pains in other joints, and also psychological problems such as depression and anxiety.”

Whilst anyone can get osteoarthritis, most cases affect adults over the age of 45 and it is a major cause of disability in people aged 65 and over. Women are more likely than men to suffer from the condition – often referred to as ‘wear and tear’ arthritis – especially after the age of 50.

Results from a six-month long phase 2 trial run by Paradigm Biopharma have already shown that iPPS may slow the progression of KOA.

The exploratory 61-patient phase 2 randomised, double blind, placebo-controlled trial for synovial biomarkers in knee osteoarthritis showed changes consistent with disease modifying efficacy in subjects with moderate to severe osteoarthritis. Seventy eight per cent of subjects had moderate to severe osteoarthritis of the knee.

The six-month data indicated disease modifying potential for the drug in KOA based on less cartilage loss, as measured by MRI, in the iPPS group compared to those on placebo. MRIs of the placebo group cartilage showed an increase in its loss.

Levels of synovial biomarkers of cartilage and aggrecan disintegration were down at six months in the iPPS group. The same biomarkers increased in the placebo group.

Statistically significant reductions in bone marrow lesions, measured by MRI, were seen compared to placebo, with a trend towards reduced marginal osteophytes (bone spurs) compared to an increase in the placebo group.

Paradigm is now undertaking a comprehensive global phase 3 clinical trial designed to maximise the potential of iPPS, which it will market under the name Zilosul.

To this end the company has launched a clinical trial website to facilitate current and potential trial participants and support its development programme for KOA therapy called

Here people living in either Australia or the US, can put their name forward as a potential trial participant, and find the answers to commonly asked KOA questions alongside patient support.


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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