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Bit.bio expands portfolio targeting neurological conditions

It’s products will target neurological diseases such as epilepsy, schizophrenia, autism and Alzheimer’s.

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UK-based company, Bit.bio, has developed three new human cell products for research and drug discovery in neurodegenerative and neurological diseases.

Cell coding company bit.bio has announced three additions to its product portfolio to further its research into new treatments for neurological conditions such as Alzheimer’s disease.

The products include two frontotemporal dementia (FTD) disease models that provide a scalable and reproducible system to model neurodegenerative disease in a human context

It has also announced early access to ioGABAergic Neurons with unprecedented purity to provide a human model for research into neurological diseases including epilepsy, schizophrenia, autism and Alzheimer’s.

Bit.bio’s cell products are reprogrammed from human induced pluripotent stem cells (hiPSCs) using the company’s proprietary precision reprogramming technology opti-oxTM. This announcement expands the company’s central nervous system (CNS) portfolio to four disease models and three cell types.

FTD is the second leading cause of early onset dementia following Alzheimer’s disease. Patients with FTD suffer from behaviour and personality changes and lose their ability to perform daily tasks.

Around a third of FTD cases are hereditary and have been linked to mutations in the MAPT gene. ioGlutamatergic Neurons MAPT N279K and ioGlutamatergic Neurons MAPT P301S each contain different mutations in the MAPT gene commonly observed in FTD patients.

For the first time, scientists can now use these MAPT disease model cells alongside a genetically matched control, ioGlutamatergic Neurons. This means that any experimental differences between the control and the disease model can be confidently attributed to the effects caused by the mutations in the MAPT gene, offering researchers a new window into the disease mechanisms of FTD and in identification of new potential drugs to treat it.

The disease model cells and the genetically matched control mature rapidly, are highly reproducible between batches, and have unprecedented scalability. These key features make the products ideally suited to screening applications for early drug discovery as well as for fundamental research.

Dr Mark Kotter, CEO and Founder of Bit.bio, said: “At Bit.bio our vision is to accelerate biomedical innovation and usher in a new generation of cures through precision reprogrammed human cells. These latest products take us another step closer to that vision and our momentum will continue – we’ve now launched six new products in the past six months with more to come in the new year.”

The third product announced today is ioGABAergic Neurons. GABAergic neurons are responsible for slowing down the propagation of the brain’s electrical signals. This function is essential for information to be efficiently relayed throughout the brain. GABAergic neuron dysfunction has been associated with a variety of neurological diseases, including epilepsy, schizophrenia, autism and Alzheimer’s disease.

Existing methods used to generate iPSC-derived GABAergic neurons are problematic, as the resulting cell population is heterogeneous with other neuronal cell types, leading to a lack of experimental reproducibility. ioGABAergic Neurons address these challenges allowing scientists to work with an unprecedented pure population of cells (>95 per cent purity) that are highly characterised, functional and are ready for experimentation within days.

Dr Marius Wernig, professor at Stanford and SAB member, said: “Research into neurological conditions such as FTD are at a pivotal stage. It is exciting to see the progress we are making. And whilst animal models have provided important insights, they differ considerably from human biology. This has contributed to the difficulties translating science into the clinic. 

“The reprogramming approach that my lab has developed for generating GABAergic and glutamatergic neurons, which also forms the basis of bit.bio’s cells and disease models, can help address this gap.”

Dr Farah Patell-Socha, VP Research Products at Bit.bio, added:“The launch of these products is further evidence of our robust CNS cell pipeline for research and drug discovery. Physiologically relevant human cells that perform consistently across lots are game-changing for the industry. Furthermore, this performance alleviates the need for lot-to-lot validation, translating into significant time and cost savings. These products will pave the way for high-throughput screening and drug target validation in human iPSC-derived models that was previously impossible.”

 

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Sitting still for long periods increases mortality risk, says study

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Sitting for long hours without breaks can increase risk mortality risk in older women, a new study shows.

The research, published in the Journal of the American Heart Association (JAHA), has data showing that older women who sat for 11.7 hours or more per day increased their risk of death by 30 percent, regardless of whether they exercised vigorously.

The study examined measurements of sitting and daily activity collected from hip devices worn for up to seven days by 6,489 women, aged 63 to 99, who were followed for eight years for mortality outcomes.

This data was collected  as part of a long-term national project known as the Women’s Health Initiative (WHI), which began in 1991 and is ongoing, led by Andrea LaCroix, Ph.D., M.P.H., Distinguished Professor at the Herbert Wertheim School of Public Health.

The paper is the first to apply a novel and validated machine-learned algorithm called CHAP to examine total sitting time and length of sitting bouts in relation to the risk of death.

Study co-author Steve Nguyen, PhD., M.P.H., a postdoctoral fellow at the University of California San Diego Herbert Wertheim School of Public Health and Human Longevity Science, said: “Sedentary behaviour is defined as any waking behaviour involving sitting or reclining with low energy expenditure.

“Previous techniques for calculating sedentary behaviour used cut points that identified low or absent movement. The CHAP algorithm was developed using machine-learning, a type of artificial intelligence, that enhanced its ability to accurately distinguish between standing and sitting.”

Fine-tuning “sitting” enabled Nguyen to parse total sitting time and usual sitting bout durations.

Sedentary behaviour is a health risk because it reduces muscle contractions, blood flow and glucose metabolism.

Exercise cannot undo these negative effects, according to the study, whether women participated in low or high amounts of moderate-to-vigorous intensity physical activity, they showed the same heightened risk if they sat for long hours.

LaCroix explained: “When you’re sitting, the blood flow throughout your body slows down, decreasing glucose uptake. Your muscles aren’t contracting as much, so anything that requires oxygen consumption to move the muscles diminishes, and your pulse rate is low.

“If I take a brisk long walk for an hour but sit the rest of the day, I’m still accruing all the negative effects on my metabolism.”

Based on the research, LaCroix makes the following recommendation: “The risk starts climbing when you’re sitting about 11 hours per day, combined with the longer you sit in a single session. For example, sitting more than 30 minutes at a time is associated with higher risk than sitting only 10 minutes at a time. Most people aren’t going to get up six times an hour, but maybe people could get up once an hour, or every 20 minutes or so. They don’t have to go anywhere, they can just stand for a little while.”

However, Nguyen points out that not all sitting is the same.

“Looking beyond conditions like cardiovascular disease, we start thinking about cognitive outcomes, including dementia,” he said.

“There are cognitively stimulating activities that can result in sedentary behavior, like sitting while studying a new language. Is sedentary behavior in that context overall bad for a person? I think it’s hard to say.” Nguyen has recently received a National Institute of General Medical Sciences K99 award for 12 months of mentored research to look at protein signatures of physical activity and how they relate to dementia.

LaCroix added: “We’ve created this world in which it’s so fascinating to sit and do things. You can be engrossed by TV or scroll on your Instagram for hours. But sitting all the time isn’t the way we were meant to be as humans, and we could reverse all of that culturally just by not being so attracted to all the things that we do while sitting.”

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High risk of hospital readmission after surgery among older Americans

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A study finds an increased risk of hospital readmission for older Americans within 180 days of undergoing major surgery — a risk that is particularly acute for individuals who are frail or have dementia.

The findings from researchers at the University of Yale, were published in the journal JAMA Network Open.

Previous research by the same team demonstrated that major surgery is a common event for older Americans and also demonstrated a heightened mortality risk within one year of major surgery for people who are age 65 and older.

The new study is the first to describe both the short-term risk (within 30 days) and longer-term risk (within 180 days) of hospital readmission for older Americans who have recently had major surgery.

The study looked at hospital readmission among a nationally representative sample of 1,477 older Americans, not living in nursing homes, who had at least one major surgery between 2011 and 2018. More than one in four (27.6 per cent) had a readmission to the hospital within 180 days after major surgery; nearly one in eight (11.6 per cent) were readmitted within just 30 days.

Dr. Robert D. Becher, associate professor of surgery at Yale School of Medicine and co-senior author of the study, commented: “Prior to now, data on longer-term readmissions after major surgery in older persons have been lacking. This is problematic, as older persons undergoing major surgery represent a large and growing population.

“These readmission rates are high. And this study adds to our understanding of what it means to recover from major surgery as an older person.”

The numbers are even higher for those with geriatric-specific conditions such as frailty and dementia. Frail patients were readmitted within 180 days at a rate of 36.9 per cent; patients with probable dementia were readmitted at a rate of 39 per cent; and patients 90 years old and older were readmitted at a rate of 36.8 per cent.

Dr. Thomas M. Gill, the Humana Foundation Professor of Geriatric Medicine at Yale and co-senior author of the study, said: “These findings reenforce the importance of enhanced preoperative recognition of frailty and dementia in older persons and may inform patient and family expectations — and surgical decision making — about postoperative trajectories in the setting of these geriatric conditions.”

The issue of hospital readmission looms large in the USS health care system for a variety of reasons.

In 2018 alone, readmission costs totalled more than $50 billion, the researchers said. This was driven, in part, by the nearly 3.8 million 30-day hospital readmissions that year. The vast majority of those patients are Medicare beneficiaries aged 65 and older.

“From a patient perspective, the most important outcome among older persons with multiple conditions is maintaining independence and function. And we know that being readmitted to the hospital after major surgery can negatively impact that independence and function,” Becher said.

“So these new data put into perspective just how common hospital readmissions, and their negative downstream consequences, are to older persons.”

The researchers said the next steps in their examination of the issue will be to further understand why vulnerable older persons have such high readmission rates and suggest meaningful ways to minimise the risk of readmission.

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Risk factors for frailty in old age different in men and women, finds study

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A study conducted by researchers at the Federal University of São Carlos (UFSCar) in Brazil and University College London (UCL), found the factors that increase the risk of frailty in old age to be different in men and women.

The study, which was funded by FAPESP, is published in the journal Archives of Gerontology and Geriatrics.

According to the results, osteoporosis, low weight, heart disease, and poor hearing increased the risk of frailty in men, while a high level of fibrinogen (a marker of cardiovascular disease) in the blood, diabetes and stroke were associated with a higher risk of frailty in women.

The findings were based on an analysis of data from 1,747 participants in the English Longitudinal Study of Ageing (ELSA), an ongoing population survey that explores the dynamic relationships between health, functioning, social networks and economic status in people aged 50 and over who reside in England. ELSA began in 2002. These participants were interviewed and assessed every four years between 2004 and 2016.

The researchers selected participants aged 60 or more who initially did not have frailty syndrome and were not classified as pre-frailty (with only one or two of the above factors).

Frailty syndrome is characterised by the presence of three or more of the following factors: involuntary weight loss, fatigue, muscle weakness, slow gait, and a low level of physical activity. It is more common in women than men, partly because of women’s greater life expectancy.

Tiago da Silva Alexandre, last author of the article and a professor in UFSCar’s Department of Gerontology, explained: “Frailty syndrome serves as a warning sign of the possibility of a negative outcome in an older person. We used to think of frailty as having a single pathway in the elderly, but our study shows there are several routes. The differences between men and women in this regard are important for policymakers to take into account. They should influence primary health care and could result in more gender-specific action plans and intervention for older people.”

Frailty syndrome has a phenotype, he explained – a set of easily identifiable signs and symptoms designed to identify older people with a heightened risk of falls, hospitalisations, incapacitation, and early death.

“Our study went back a few steps before this process begins to find out which characteristics may lead to frailty during the lives of these older people. When we think about aging and the quality of life in old age, it’s very important to identify the main risk factors so as to be able to foresee problems and formulate public policy for men and women,” he added.

According to Dayane Capra de Oliveira, first author of the article, although frailty as a tool is based on biology, sex-related differences in risk factors for development of the syndrome are mainly associated with the different social roles of men and women, and with their different degrees of access to resources during their lives.

“Another key aspect is that frailty is a multifactorial condition. While socioeconomic factors, skeletal muscle disorders, heart disease and low weight appear to underlie frailty in men, in women the process appears to be driven mainly by cardiovascular and neuroendocrine disturbances,” Oliveira said.

Differences and similarities

According to the researchers, while some risk factors for frailty are the same for men and women – including old age, low educational attainment, sedentarism and depression, for example – differences in body composition and fat deposition throughout life and especially in old age may lead directly or indirectly to the appearance of components of frailty, such as metabolic alterations that culminate in the development of diseases, which in turn increase the risk of frailty.

Alexandre said: “Our study is based on data for people now aged 60 or more and living in England. We don’t know how these sex-based differences will play out in future generations. However, the fact is that the men in the cohort we studied were more exposed to several kinds of working conditions considered risk factors for diseases. Their diet was less healthy. They didn’t go to the doctor as much as the women [so that there was less early diagnosis]. They drank more and were more exposed to other substances that increased the risk of cardiovascular disease and heart attack.”

Women are more affected by chronic diseases, which are not as lethal but can be incapacitating.

He added: “The sex-based differences are a lifelong backdrop and culminate in different ageing processes, different causes of death or disability, and different kinds of frailty in men and women.”

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