Robots help put brakes on inflammatory diseases.

Necroptosis atlas

Atlas of necroptotic pathway expression in human intestinal crypts.  CREDIT WEHI

A groundbreaking study conducted by WEHI has unveiled revolutionary techniques for detecting necroptosis, a crucial factor in various inflammatory diseases such as psoriasis, arthritis, and inflammatory bowel disease. These findings signify a significant leap forward in the accurate diagnosis of necroptosis and present practical methods that can be replicated in hospitals worldwide. This offers a promising avenue for the development of new treatment approaches for inflammatory diseases and has the potential to significantly improve the lives of millions of individuals globally.

At a glance

  • Necroptosis is a form of cell death, one of the body’s natural processes for removing unwanted or dangerous cells. In some people, this process can go awry and trigger disease.
  • Researchers have developed automated techniques to pinpoint when and where necroptosis happens in patients.
  • The findings could lead to better diagnosis and personalised treatments for numerous inflammatory diseases.

Catching the cell death ‘culprit’

Necroptosis, a type of cell death associated with inflammation, has long been suspected as the ‘culprit’ driving many debilitating diseases associated with gut, skin, and lung conditions. However, identifying which cells undergo necroptosis in real-life situations has been difficult.

WEHI’s Dr Andre Samson, co-leader of the study, said the findings had cracked a challenging and hotly debated area of science.

“It is so exciting to finally be able to catch necroptosis in the act,” Dr Samson said.

The new methods precisely located necroptosis in patients with ulcerative colitis or Crohn’s disease, providing critical insights into how this cell death process contributes to various inflammatory diseases.

The findings further revealed that necroptosis responds not just to inflammation, but also to bacterial changes or immune issues.

“Among other results, we also found that when proteins like Caspase-8 cluster together in cells, it’s a sign of necroptosis,” Dr Samson said.

“This is a major leap forward in our journey to eventually delivering new medicines that can treat a long list of inflammatory diseases by stopping necroptosis.

“It helps us understand when and where necroptosis happens, both in healthy and disease situations.”

Lifesaving atlas for the future

The research opens new windows to understanding the intricate mechanisms of cell death and its connection to inflammatory diseases.

The team behind the study referred to their work as an “atlas of necroptosis” because it provides a precise map of which cells in the body are capable of undergoing necroptosis.

“We can now confidently visualise where and when necroptotic cell death can happen in the body,” said Prof Murphy.

In the spirit of collaboration, Prof Murphy emphasised that a key goal of the study was to discover a solution that could be easily replicated in both the laboratory and clinical settings.

“Most importantly, researchers and clinicians around the world will now be able to use these new methods, especially as liquid handling robots for immunostaining are common in hospitals and pathology departments worldwide,” he said.

“The next phase is to use these robotic methods to advance our understanding of which diseases could benefit from medicines that block necroptosis.”

The successful development of these automated methods to detect necroptosis in patients is just the beginning. The research team plans to extend their techniques to investigate other gut diseases, such as coeliac disease, and a broader range of inflammatory conditions of the skin, lung and kidney.

People who care for loved ones with arthritis carry an economic burden.

Informal carers looking after a loved one with arthritis are financially worse off than non-carers to the sum of $388 million, Griffith University research has discovered
Informal carers looking after a loved one with arthritis are financially worse off than non-carers to the sum of $388 million, Griffith University research has discovered.

Informal carers looking after a loved one with arthritis are financially worse off than non-carers to the sum of $388 million, Griffith University research has discovered.

That figure will increase to $576.9 million by 2030, painting a stark future for informal carers who are not in the labour force and do not receive any monetary compensation in exchange for the care provided.

Informal carers are also less likely to participate in the workforce due to the demands of their caregiving duties.

Professor Lennert Veerman from Griffith’s School of Medicine and Dentistry co-authored a paper with researchers from Macquarie University that assessed the economic burdens associated with the increasing number of Australians living with chronic disease—arthritis.

Arthritis, a musculoskeletal disease, can be a costly disease to treat due to its high prevalence and the lifelong nature of the illness.

Professor Veerman said the research aimed to forecast the economic losses related to caring for people with arthritis from 2015-2030.

“People caring for someone with arthritis earn about $1,000 per week less than similar people who do not have caring responsibilities,” he said.

“Unfortunately, that figure is projected to increase by 22 per cent by 2030, impacting informal carers more economically.

“This equates to a total economic loss of around half a billion dollars annually, and reduced tax revenue is about $100 million annually.

“This is further proof that our informal carers are economically worse off than employed non-carers, especially when the future economic impact of informal carers is projected to increase.”

The paper has prompted researchers to encourage decision-makers to increase their efforts to prevent chronic disease, improve quality of life, and increase economic growth.

The paper ‘Economic impact of informal caring for a person with arthritis in Australia from 2015 to 2030: a microsimulation approach using national survey data’ has been published in BMJ Open.

Informal carers looking after a loved one with arthritis are financially worse off than non-carers to the sum of $388 million, Griffith University research has discovered.

That figure will increase to $576.9 million by 2030, painting a stark future for informal carers who are not in the labour force and do not receive any monetary compensation in exchange for the care provided.

Informal carers are also less likely to participate in the workforce due to the demands of their caregiving duties.

Professor Lennert Veerman from Griffith’s School of Medicine and Dentistry co-authored a paper with researchers from Macquarie University that assessed the economic burdens associated with the increasing number of Australians living with chronic disease—arthritis.

Arthritis, a musculoskeletal disease, can be a costly disease to treat due to its high prevalence and the lifelong nature of the illness.

Professor Veerman said the research aimed to forecast the economic losses related to caring for people with arthritis from 2015-2030.

“People caring for someone with arthritis earn about $1,000 per week less than similar people who do not have caring responsibilities,” he said.

“Unfortunately, that figure is projected to increase by 22 per cent by 2030, impacting informal carers more economically.

“This equates to a total economic loss of around half a billion dollars annually, and reduced tax revenue is about $100 million a year.

“This is further proof that our informal carers are economically worse off than employed non-carers, especially when the future economic impact of informal carers is projected to increase.”

The paper has prompted researchers to encourage decision-makers to increase their efforts to prevent chronic disease, improve quality of life, and increase economic growth.

Joints that could heal themselves? Researchers could get there in five years.

A quest to end osteoarthritis

Stephanie Bryant, a researcher in the BioFrontiers Institute at the University of Colorado Boulder, will be receiving a substantial grant to find a possible cure for osteoarthritis works with Graduate Research Assistant Laurel Stefani, a Biomedical Engineering PhD major from Richardson, TX. (Photo by Casey A. Cass/University of Colorado)

Imagine a day when joints could heal themselves.

At the first sign of a creaky knee, patients could get a single shot in the joint that would not only stop their cartilage and bone from eroding but also kick-start their regrowth. In more advanced cases, that shot might also deliver a biomaterial repair kit to patch holes in tissue. If multiple joints ached, an annual IV infusion could ferry regenerating therapies to all of them at once.

This may seem like a dream to the 32.5 million people who suffer from osteoarthritis. This week, the Advanced Research Projects Agency for Health (ARPA-H) awarded up to $39 million to a University of Colorado Boulder-led team of scientists to work toward making it a reality. 

The Novel Innovations for Tissue Regeneration in Osteoarthritis (NITRO) program was the first created under ARPA-H, a new federal agency to support “high-impact solutions to society’s most challenging health problems.” 

With the cash infusion, a dream team of engineers, medical scientists, and veterinarians from CU Boulder, the CU Anschutz Medical Campus, and Colorado State University can aggressively make the final push toward a goal many have spent their entire careers pursuing. 

“Our goal is to develop a suite of noninvasive therapies that can end osteoarthritis within five years,” said project leader and Principal Investigator Stephanie Bryant, PhD, a professor in the Department of Chemical and Biological Engineering, Materials Science and Engineering, and the BioFrontiers Institute at CU Boulder. “It could be an absolute game-changer for patients.”

An epidemic without a cure

Osteoarthritis is the third most common disease in the U.S. and affects roughly one in six people over age 30 worldwide.
 
The disease causes cartilage—the buffering tissue that keeps bones from grinding together—to decay. Over time, bone is damaged, too, reshaping the joint and making movement painful. 
 
Age and obesity increase risk, and rates are on the rise as the U.S. population ages and grows more sedentary. At present, patients are generally limited to two options: Treat the pain and, when that is no longer adequate, surgically replace the joint. There is no cure.

“To truly address osteoarthritis, you have to address both the biology and the structural problem,” said co-principal Investigator Michael Zuscik, PhD, a professor and research vice chair in the Department of Orthopedics at the Anschutz Medical Campus. “This unique Colorado dream team we have put together has the multidisciplinary expertise and now the resources to tackle both at once. We can approach curing the disease like never before.”

Zuscik spent 15 years developing and testing a drug that addresses the biology, nudging cartilage and bone cells to produce proteins needed to rebuild. While promising, it must be injected every day.

Meanwhile, Bryant, a materials scientist, has worked for 26 years to develop three-dimensional gel-like biomaterials that can slip into the cracks of torn cartilage or worn bone. These materials provide supportive scaffolding — like the joists of a new building—for the body’s own cells to migrate to.

CSU scientists have been working for years to perfect gene therapy techniques that control inflammation and hasten cartilage healing.

The team now faces an engineering challenge – to devise methods to deliver these technologies to the body together, in a way that provides lasting benefit and treats multiple joints at once if needed.

A one-shot medical breakthrough

To that end, the team is developing nanoparticles that could be administered intravenously, serving as Trojan horses that migrate to inflamed sites and deliver a regenerative medicine cocktail that enables joints to heal.

The team hopes to ultimately commercialize three innovations: a healing shot; an injury-patching hydrogel; and an annual infusion for systemically treating osteoarthritis. 

When it’s time for trials, co-Principal Investigator Laurie Goodrich, DVM PhD, a veterinary clinician scientist and director of the Orthopaedic Research Center at CSU’s Translational Medicine Institute, will lead the charge in animals. 

“CSU’s expertise in veterinary medicine will play a crucial role in helping to move this science to the next step,” said Goodrich. “It’s humbling to be a part of it.”

Within 3.5 years, the team hopes to begin conducting trials in human patients. 

However, it’s not enough to simply develop such treatments, said Co-Principal Investigator Karin Payne, PhD, associate professor of orthopedics at CU Anschutz.

“At the core of this, the goal is to develop a therapy that’s going to be available to all Americans, not just a privileged few,” Payne said, noting that researchers will include a demographically diverse group of study participants and minimize cost to make the treatments as affordable as possible.

How to deal with autoimmune disease flares- A Rheumatologist POV

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