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Personalisation may improve prostate cancer screening accuracy

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Scientists have moved a step closer to genetically personalised prostate cancer screening.

The most common assessment test for the cancer, which mainly affects men over the age of 50, is prostate-specific antigen (PSA) screening which often erroneously indicates signs of the disease.

But a joint team at UC San Francisco and Stanford University, both in the US, have come up with a method they believe will make screening more accurate by calibrating PSA levels to each man’s genetics.

They say applying this type of personalisation could significantly reduce overdiagnosis and better predict aggressive disease. In addition to the regular blood-based PSA test, such customised screening would need a germline genetic test, usually conducted on blood, saliva, or cheek swab samples, to look for inherited genetic variants that affect PSA levels.

Whilst raised PSA levels can be a sign of a cancerous prostate tumour, they can also be caused by other circumstances, like infection, an enlarged prostate, inflammation or simply old age.

In a study published in Nature Medicine, UCSF researchers and their collaborators conducted a large genome-wide association study of PSA in more than 95,000 men without diagnosed prostate cancer. This identified more than 80 novel PSA- associated variants.

They set out to discover whether accounting for genetic factors that cause variations in the levels of PSA that are not attributable to cancer could help improve PSA screening.

Senior author of the study, John Witte, a professor of epidemiology and population health and of biomedical data sciences at Stanford, said: “Some men have higher PSA levels due to their genetics. They don’t have cancer, but the higher PSA level leads to a cascade of unnecessary medical interventions like biopsy.”

Linda Kachuri, a former postdoctoral scholar in the Department of Epidemiology and Biostatistics at UCSF and lead author of the study, added: “PSA levels represent the main diagnostic biomarker for prostate cancer. This test is widely used but not currently implemented as part of a formal screening programme.

“Because of its poor sensitivity and specificity, PSA testing can often lead to detecting latent disease or, in some cases, missing aggressive tumours.”

The researchers identified 128 sites in the genome that can affect a person’s inherent PSA level. They developed a way to calculate PSA that accounts for an individual’s normal genetic variations at these sites – known as a PSA polygenic score, which is a quantitative way of measuring someone’s genetic predisposition for a trait in a single value. In this case, the trait is a higher baseline PSA level.

The researchers leveraged the new data to build a genome-wide polygenic score for PSA.

The polygenic score captured each individual’s genetic predisposition to high PSA levels. The team found the polygenic score was strongly associated with PSA levels in validation cohorts and was not associated with prostate cancer. This confirmed that it reflects benign PSA variation.

To examine whether the polygenic score could improve the detection of clinically significant disease and reduce overdiagnosis, each person’s PSA values were adjusted based on their unique genetic profile.

Dr Kachuri said: “PSA values personalised in this way are more likely to reveal changes in PSA due to prostate cancer because they are corrected for the influence of inherited genetics.”

Applying a correction to PSA levels improved the accuracy of biopsy referral decisions. Roughly 30% of men could have avoided biopsy, though adjusted PSA levels would have missed approximately 9% of positive cell samples.

Most of the latter cancers were low-grade disease that did not require treatment, but the researchers admit the misclassifications point to room for improving the polygenic score.

Dr Kachuri said: “We showed that genetic correction of PSA levels has the potential to both reduce unnecessary biopsies and improve our ability to detect tumours with a more aggressive profile. We hope that our findings represent a step forward in developing informative screening guidelines and reducing the diagnostic grey area in PSA screening.”

While the study was very large, almost 90% of the participants were of predominantly European ancestry.

According to Dr Kachuri, this represents a key limitation because the composition of the study doesn’t fully reflect the patient population impacted by prostate cancer.

The team is now working on a larger study in association with the Million Veteran Program, a US-based national research project launched in 2011 looking at how genes, lifestyle, military experience, and exposures affect health and wellness in former members of the armed forces. More than 950,000 veterans have now joined the MVP.

Nearly 1.5 million new prostate cancer cases are diagnosed each year globally and it is the fifth leading cause of cancer death among men. In the US, one in nine men will be diagnosed with prostate cancer, and one in 40 will die from it.

With a disease as prevalent as prostate cancer the researchers believe even a small improvement in screening could save lives.

Dr Kachuri concluded: “We hope to be able to share findings soon from our efforts to conduct larger and more diverse studies of PSA genetics.”

 

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Mole rat gene extends mouse lifespan

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A mole rat gene inserted into mice extended lifespan and improved health, findings that may point to new ways of supporting healthier ageing.

The gene increased production of a large form of hyaluronan, a naturally occurring gel-like substance between cells that helps tissue repair and cell-to-cell communication.

Mice carrying the naked mole rat version of the gene showed an approximately 4.4 per cent increase in median lifespan, alongside multiple markers of healthier ageing.

Naked mole rats have become a focus of ageing research because they combine an exceptional lifespan with unusual resistance to many age-linked diseases, including cancer.

Researchers at the University of Rochester traced part of that resilience to hyaluronan.

The molecule’s effects depend on its size: large forms are often linked to anti-inflammatory and tissue-protective behaviour, while smaller fragments can act as danger signals that increase inflammation.

Vera Gorbunova, professor of biology and medicine at the University of Rochester in the US, said: “Our study provides a proof of principle that unique longevity mechanisms that evolved in long-lived mammalian species can be exported to improve the lifespans of other mammals.”

The engineered mice were better protected against both spontaneous tumours and chemically induced skin cancer.

They also showed reduced inflammation across tissues, a notable finding because persistent low-grade inflammation, sometimes called inflammaging, is widely seen as one of the central drivers of age-related decline.

The research also linked the large form of hyaluronan to age-related gut health. As animals age, the gut barrier can become leakier, allowing inflammatory triggers to pass into the bloodstream.

The engineered mice showed protection against this deterioration.

Follow-up work found abundant high-molecular-mass hyaluronan across multiple species of subterranean mammals, often absent in closely related above-ground species, suggesting it may be part of a broader evolutionary toolkit for surviving long lives under harsh conditions.

The team said gene transfer is not the end goal. Gorbunova said: “It took us 10 years from the discovery of HMW-HA in the naked mole rat to showing that HMW-HA improves health in mice.”

“Our next goal is to transfer this benefit to humans.”

Two practical routes are being pursued: increasing production of the large form of hyaluronan, or slowing its breakdown.

Andrei Seluanov, who co-leads the research, said: “We already have identified molecules that slow down hyaluronan degradation and are testing them in pre-clinical trials.”

One candidate identified through screening is delphinidin, a plant pigment found in various fruits and vegetables.

In tests, it was found to increase levels of the large form of hyaluronan in cells and mouse tissues, reduce migration and invasion in multiple cancer cell lines, and suppress melanoma metastasis in mice.

However, the researchers acknowledged the approach has limits. A later study found that mice expressing the naked mole rat gene showed improvements in several late-life health measures but did not show protection from age-related hearing loss, suggesting some organs may be less reachable by this pathway than others.

The Rochester team said turning these findings into human therapies will likely depend on precision: maintaining the right molecular form of hyaluronan, targeting the right balance of production versus breakdown, and monitoring carefully for trade-offs as different tissues respond in different ways.

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AI can predict Alzheimer’s with almost 93% accuracy, researchers say

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Alzheimer’s AI can predict the disease with nearly 93 per cent accuracy using more than 800 brain scans, researchers say.

The system identified anatomical changes in the brain linked to the onset of the most common form of dementia, a condition that gradually damages memory and thinking.

The findings build on years of research suggesting AI could help spot early Alzheimer’s risk, predict disease and identify patients whose condition has not yet been diagnosed.

Benjamin Nephew, an assistant research professor at the Worcester Polytechnic Institute in Massachusetts, said: “Early diagnosis of Alzheimer’s disease can be difficult because symptoms can be mistaken for normal ageing.

“We found that machine-learning technologies, however, can analyse large amounts of data from scans to identify subtle changes and accurately predict Alzheimer’s disease and related cognitive states.”

The study used MRI scans, a type of detailed brain imaging, from 344 people aged 69 to 84.

The dataset included 281 scans showing normal mental function, 332 with mild cognitive impairment, an early stage of memory and thinking decline, and 202 with Alzheimer’s.

The scans covered 95 of the brain’s nearly 200 distinct regions and used an AI algorithm to predict patients’ health.

Being able to use AI to help diagnose Alzheimer’s earlier could give patients and doctors crucial time to prepare and potentially slow the progression of the disease.

The analysis showed that one of the top predictive factors was brain volume loss, or shrinkage, in the hippocampus, which helps form memories, the amygdala, which processes fear, and the entorhinal cortex, which helps provide a sense of time.

This pattern held across age and sex, with both men and women aged 69 to 76 showing volume loss in the right part of the hippocampus, suggesting it may be an important area for early diagnosis, the researchers noted.

However, the research also found that the way brain regions shrink differs by sex.

In females, volume loss occurred in the brain’s left middle temporal cortex, which is involved in language and visual perception. In males, it was mainly seen in the right entorhinal cortex

The researchers believe this could be linked to changes in sex hormones, including the loss of oestrogen in women and testosterone in men.

These conclusions could help improve methods of diagnosis and treatment going forward, Nephew said.

More than 7.2m Americans are living with Alzheimer’s, according to the Alzheimer’s Association.

More research is being done to reveal other impacting factors.

Nephew said: “The critical challenge in this research is to build a generalisable machine-learning model that captures the difference between healthy brains and brains from people with mild cognitive impairment or Alzheimer’s disease.”

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Vision implant firm raises US$230m

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A vision implant firm has raised US$230m as it seeks approval in Europe and the US for a device that restored sight in a small clinical trial.

The Alameda, California-based startup said the funding would support commercialisation of its Prima device.

It said an upcoming launch is planned in Europe and that it would become the first brain computer interface company to have a vision restoration device on the market.

A clinical trial in Europe found the small implant could work as artificial photoreceptors in the retina to restore functional central vision.

The implant is placed under the retina to replace the function of light-sensitive cells lost to disease. A special pair of glasses with an embedded camera and infrared projector sends light signals to the implant.

The study assessed the system in people with advanced dry age-related macular degeneration.

Of the 38 patients who received an implant, 32 were assessed at 12 months. Results showed the device led to a clinically meaningful improvement in visual acuity in 26 people.

The patients were able to read letters, numbers and words, according to the company.

Science Corporation said it has submitted a CE mark application to the European Union and applied to the US Food and Drug Administration for regulatory approval.

Darius Shahida, chief strategy officer, said: “Our imperative is to become the first BCI company to scale and achieve profitability.”

Founded in 2021, the company has now raised about US$490m in total. It said it is expanding its clinical trial programme to include other retinal diseases, such as Stargardt disease and retinitis pigmentosa.

The Series C round included existing investors Khosla Ventures, Lightspeed Venture Partners, Y Combinator, IQT and Quiet Capital.

Science Corporation said demand for the round exceeded its capital needs, with funds also earmarked for expanding research, manufacturing infrastructure and operations.

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