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Liver tumours partially destroyed with sound do not return

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Zhen Xu and Tejaswi Worlikar discuss the histotripsy ultrasound array transducer they use (Photo by Marcin Szczepanski)

Non-invasive sound technology developed at the University of Michigan breaks down liver tumours in rats, kills cancer cells and spurs the immune system to prevent further spread – an advance that could lead to improved cancer outcomes in humans.

By destroying only 50 to 75 percent of liver tumour volume, the rats’ immune systems were able to clear away the rest, with no evidence of recurrence or metastases in more than 80 per cent of animals.

“Even if we don’t target the entire tumour, we can still cause the tumour to regress and also reduce the risk of future metastasis,” said Zhen Xu, professor of biomedical engineering at U-M and corresponding author of the study in Cancers.

Results also showed the treatment stimulated the rats’ immune responses, possibly contributing to the eventual regression of the untargeted portion of the tumour and preventing further spread of the cancer.

The treatment, called histotripsy, non-invasively focuses ultrasound waves to mechanically destroy target tissue with millimetre precision.

The relatively new technique is currently being used in a human liver cancer trial in the United States and Europe.

In many clinical situations, the entirety of a cancerous tumour cannot be targeted directly in treatments for reasons that include the mass’ size, location or stage.

To investigate the effects of partially destroying tumours with sound, this latest study targeted only a portion of each mass, leaving behind a viable intact tumour.

It also allowed the team, including researchers at Michigan Medicine and the Ann Arbor VA Hospital, to show the approach’s effectiveness under less than optimal conditions.

“Histotripsy is a promising option that can overcome the limitations of currently available ablation modalities and provide safe and effective noninvasive liver tumour ablation,” said Tejaswi Worlikar, a doctoral student in biomedical engineering.

“We hope that our learnings from this study will motivate future preclinical and clinical histotripsy investigations toward the ultimate goal of clinical adoption of histotripsy treatment for liver cancer patients.”

Improved outcomes

Liver cancer ranks among the top 10 causes of cancer related deaths worldwide and in the US. Even with multiple treatment options, the prognosis remains poor with five-year survival rates less than 18 per cent in the US.

The high prevalence of tumour recurrence and metastasis after initial treatment highlights the clinical need for improving outcomes of liver cancer.

Where a typical ultrasound uses sound waves to produce images of the body’s interior, U-M engineers have pioneered the use of those waves for treatment.

And their technique works without the harmful side effects of current approaches such as radiation and chemotherapy.

“Our transducer, designed and built at U-M, delivers high amplitude microsecond-length ultrasound pulses—acoustic cavitation—to focus on the tumor specifically to break it up,” Xu said. “Traditional ultrasound devices use lower amplitude pulses for imaging.”

The microsecond long pulses from U-M’s transducer generate micro bubbles within the targeted tissues – bubbles that rapidly expand and collapse.

These violent but extremely localized mechanical stresses kill cancer cells and break up the tumour’s structure.

Since 2001, Xu’s laboratory at U-M has pioneered the use of histotripsy in the fight against cancer, leading to the clinical trial #HOPE4LIVER sponsored by HistoSonics, a U-M spinoff company.

More recently, the group’s research has produced promising results on histotripsy treatment of brain therapy and immunotherapy.

The study was supported by grants from the National Institutes of Health, Focused Ultrasound Foundation, VA Merit Review, U-M’s Forbes Institute for Discovery and Michigan Medicine-Peking University Health Sciences Center Joint Institute for Translational and Clinical Research.

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Early Alzheimer’s prediction platform secures €21 million investment

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PREDICTOM Dag Aarsland. Photo: Frida Moberg.
PREDICTOM's Dag Aarsland. Photo: Frida Moberg.

The project aims to identify people at risk of dementia before symptoms appear.

More than 7 million people are living with dementia in the EU. This number is projected to double, reaching 14 million by 2050.

There is currently no cure for Alzheimer’s disease. Although the search for potential treatments is showing promise, it is anticipated that these medications will be most effective in the early stages of the disease.

The recently launched AI screening platform, PREDICTOM aims to identify individuals at risk of developing dementia, even before symptoms manifest.

The cognitive and biomarker screening platform has this week announced it will be backed by €21 million in funding, with €8 million from the EU, €9 million from industry and €4 million from UKRI.

A consortium of 30 partners from academia, business, civil society and hospitals is steering the project. The Consortium includes partners from 15 countries across Europe, Asia and America and is led by Stavanger University Hospital.

Dag Aarsland, Professor of Old Age Psychiatry at King’s College London and research lead at Stavanger University Hospital, is the leading the project.

“Detecting early signs of dementia is key to slowing its progression. Unfortunately, a majority of those at risk are not identified in time. Our platform seeks to change this by enabling early discovery, allowing timely intervention and preventative treatment,” Aarsland said.

A crucial aspect of PREDICTOM is that much of the screening can be performed by the patients themselves in the comfort of their homes.

By initiating the process at home, the project aims to reduce strain on healthcare services and associated costs. Biomarkers, including saliva, stool, digital markers and blood via prick-tests, will be collected at participants’ homes or GP offices, streamlining a process traditionally carried out in hospitals or specialised clinics.

More than 4000 participants will partake in PREDICTOM’s trial project. The samples will be based on a pool of people from previous initiatives like PROTECT UK, PROTECT Norway and Radar-AD, as well as people from the catchment area of other participating centres in Germany, France, Switzerland, Belgium and Spain.

“If our project succeeds, there will be significant savings in both cost and time,” Aarsland said

After the home collection, samples will be sent to PREDICTOM, where their platform will process the participant data, integrating blood, cerebrospinal fluid, imaging, electrophysiological and digital biomarkers.

AI algorithms will generate risk assessments, early diagnoses and prognoses, laying the foundation for early intervention and treatment.

This project is part of the Innovative Health Initiative (IHI), a public-private partnership (PPP) between the European Union and the European life science industries.

“We are very pleased to have such a robust team with top notch expertise spanning diverse fields, including IT, AI, medicine, ageing research and professionals from both small and large businesses,” Aarsland added.

The project runs from 1st November 2023 to 31st October 2027.

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New partnership to bring dementia-specific programmes to Washington State

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Washington state dementia

The partnership will bring non-pharmacological interventions for dementia and alternatives to high-cost drugs to patients across Washington State.

A new partnership between brain health company, Together Senior Health and accountable care organisation, Rainier Health Network,

The partnership will introduce Together’s suite of dementia-specific programs, including in-home virtual interventions, to patients across Rainier Health Network in Washington state where the organisation oversees the healthcare of over 60,000 Medicare patients.

Alzheimer’s and related dementias affect more than 6.7 million Americans with 14 million projected cases by 2060. The associated healthcare costs for individuals with dementia are among the highest of any condition. Payers and providers face significant challenges in managing this expanding population.

According to a recent survey conducted by Sage Growth Partners, 77 per cent of health plans and value-based care organizations agree the need to address the growing cost of ADRD is urgent or very urgent; however, only 4 per cent have a fully-developed solution in place to support this population.

Approximately half of those surveyed also indicated a concern with the costs of Leqembi and other high-cost pharmaceuticals.

Together’s Moving Together programme offers a non-pharmacological intervention for dementia and a safe alternative to high-cost drugs that are not clinically appropriate for many dementia patients and have potential side effects.

The programme allows payers and risk-bearing healthcare organisations to more effectively manage patients. Together Senior Health says the programme results in improved engagement, reduced costs and improved health outcomes.

Recently, the company has been gaining industry traction. In addition to its partnership with Rainer Health Network, the firm is affiliated with the likes of VNS Health, VillageMD and the Alzheimer’s Association.

“Supporting our members with Alzheimer’s disease and related dementias is critical,” said Dr Francis Mercado chief medical officer and board chair at Rainier Health Network.It’s a vulnerable population and Together Senior Health’s Moving Together™ solution is a proven, natural way to improve their lives and control costs.”

Together’s Moving Together™ programme is based on over ten years of clinical research in neuroscience with the University of California, San Francisco (UCSF) and the National Institutes of Health (NIH).

Results from Together’s randomised control trial show statistically significant improvements in quality of life for individuals with cognitive decline and in caregiver ability to manage stress. The data also shows a reduction in falls and proven annual cost savings of up to $4,300 per participant per year.

Caregivers in the programme have also benefited, reporting enhanced caregiving skills.

Together is in the process of commercialising RADAR, its proprietary dementia identification and stratification algorithm. The algorithm helps payors and risk-bearing healthcare organisations identify people at highest risk for Alzheimer’s disease, dementia and cognitive decline using claims data, electronic health record information and other relevant data.

“We are proud of the positive impact Together is making on the lives of those affected by dementia and are excited to partner with one of the nation’s premier ACOs to extend dementia-specific programs to its patients,” said Alissa Meade, CEO of Together Senior Health.

“Rainier Health Network, Virginia Mason Franciscan Health and Together share a deep commitment to providing holistic dementia solutions that enrich the lives of participants while empowering forward-thinking, risk-bearing organizations to engage and manage this rapidly growing patient population effectively.”

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One in 25 carry genotype associated with shortened lifespan

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Genotype associated with shortened lifespan found in 1 in 25.
Kari Stefansson, Patrick Sulem and Brynjar Örn Jensson scientists at deCODE genetics and authors on the paper

The study used genomic data from 58,000 Icelanders and discovered the presence of a life-shortening genotype across 4 per cent of the population.

Scientists at deCODE Genetics, a subsidiary of Amgen, have published a study on actionable genotypes detected in the Icelandic population and their association with lifespan.

The researchers determined that 1 in 25 individuals carried an actionable genotype and have, on average, a shortened lifespan.

“The identification and disclosure of actionable genotypes to participants can guide clinical decision-making, which may result in improved patient outcomes,” said Kari Stefansson, author of the paper and CEO of deCODE Genetics. “This knowledge therefore has significant potential to mitigate disease burden for individuals and society as a whole.”

The study, published today in the New England Journal of Medicine, focuses on genotypes that increase the risk of a disease for which preventive or therapeutic measures have been established. These genotypes are termed actionable genotypes.

The scientists used a population-based data set, consisting of 58,000 whole-genome sequenced Icelanders, to assess the fraction of individuals carrying actionable genotypes.

Using a list of 73 actionable genes from the guidelines from the American College of Medical Genetics and Genomics (ACMG), the scientists found that 4 per cent of Icelanders carry an actionable genotype in one or more of these genes. The diseases caused by these genotypes include cardiovascular, cancer and metabolic diseases.

The study assessed the relationship between actionable genotypes and the lifespan of their carriers. The largest effect was observed among carriers of cancer-predisposing genotypes, which had three years shorter median survival than non-carriers.

A pathogenic variant in BRCA2, predisposing to breast, ovarian and pancreatic cancer, shortened lifespan by seven years and a variant in LDLR, which causes high levels of cholesterol and cardiovascular disease, shortened lifespan by six years.

“Our results suggest that the actionable genotypes identified in our study, which are all predicted to cause serious disease, may have a drastic effect on lifespan,” said Patrick Sulem author of the paper and scientist at deCODE Genetics.

The results showed that carriers of particular actionable genotypes were more likely to have died from the disease caused by these genotypes. Individuals with a pathogenic variant in BRCA2, have a seven-fold risk of dying from breast, ovarian or pancreatic cancer.

They are also 3.5 times more likely to develop prostate cancer and seven times more likely to die from prostate cancer than those who do not carry the variant.

The results of this study are among the factors that have motivated the government of Iceland to announce a nationwide effort in precision medicine.

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