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NRG Therapeutics raises £16million to advance Parkinson’s treatment

The funding will be used to advance its unique mitochondrial therapeutics through clinical trials.

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NRG Therapeutics has raised £16million in series A funding to advance its unique mitochondrial therapeutics for neurodegenerative disorders such as Parkinson’s and ALS.

NRG Therapeutics, an innovative neuroscience company targeting mitochondrial dysfunction, have announced the closing of a £16 million Series A financing raise.

NRG is applying breakthrough science in the field of mitochondrial biology to develop disease-modifying therapeutics to slow or halt the progression of neurodegenerative disorders such as Parkinson’s and ALS (also known as motor neurone disease or MND).

Parkinson’s affects around 10 million individuals worldwide and occurs as a result of the loss of specific dopamine-producing cells in the brain that control muscle movement. It is the fastest-growing neurological disorder in the world, presenting a major healthcare challenge for society. 

ALS is a rare fatal neurodegenerative disorder that typically leads to death within three to five years of diagnosis. The marketed disease-modifying treatments for ALS provide an extension in survival of approximately three to six months. Given this extension in life is modest and patients are hugely debilitated in the terminal phase disease, an improved disease-modifying medicine is desperately needed.

The Series A proceeds will be used to advance NRG’s potential first-in-class brain-penetrant small molecules through clinical studies.

What we know so far

The company’s pre-clinical pipeline includes small molecule assets which inhibit the mitochondrial permeability transition pore (mPTP) through a novel mechanism of action.

Mitochondria are the powerhouses or batteries of cells and therefore are essential for maintaining cell health. There is now a substantial body of evidence demonstrating mitochondrial failure or dysfunction is common across many degenerative diseases. Inhibition of the mPTP has been shown to protect neurons, reduce neuroinflammation, and extend survival in pre-clinical disease models.

In vitro studies have demonstrated NRG’s investigational new drugs protect mitochondria and increase the viability of human cells, and therefore have the potential to halt or significantly slow the progression of disease in individuals with Parkinson’s or ALS.

If successful in clinical trials, NRG’s therapeutics would be the first disease-modifying medicine to prevent or delay disease progression for people with Parkinson’s, where current treatments only provide management of disease symptoms. 

NRG is targeting a novel pathological mechanism in ALS, through which the protein TDP-43 triggers neuroinflammation via activation of the innate immune sensor STING, that was identified by its collaborator Professor Seth Masters, at Australia’s WEHI (Walter and Eliza Hall Institute of Medical Research). 

Following the financing, Professor Masters has joined the NRG management team as vVP of Discovery Biology. His laboratory at WEHI in Melbourne, Australia, will also include a sponsored team as part of a research agreement between NRG and WEHI.

In addition, NRG has also expanded its UK R&D and operational base with a recent move to the Stevenage Bioscience Catalyst (SBC).

The funding was led by Omega Funds and joined by additional new investor Brandon Capital and founding investor Parkinson’s Virtual Biotech.

The Parkinson’s Virtual Biotech is an international drug discovery and development programme founded in 2017 by Parkinson’s UK, the largest European charitable funder of Parkinson’s research. 

NRG Therapeutics’ co-founder and CEO, Dr Neil Miller, said: “We are excited to welcome Omega Funds and Brandon Capital as new investors and thank the Parkinson’s Virtual Biotech for its continued support. We look forward to working with them, and our expanding team and R&D partners to bring new medicines and hope to the growing number of people worldwide living with debilitating neurodegenerative disorders.”

In connection with the financing, Omega Funds Managing Director Claudio Nessi and Partner Francesco Draetta, as well as Brandon Capital Partner Jonathan Tobin, have joined the company’s Board of Directors.

Claudio Nessi, Managing Director, Omega Funds, commented: “With the ultimate impact to patients at the forefront of Omega’s process, we are focused on investing in transformative innovation with the potential to address devastating diseases with high unmet need. While drug development in neurological diseases has been challenging historically, emerging insights into disease drivers has led to somewhat of a resurgence. This is all the more important given the increasing prevalence and life-limiting effects of these debilitating diseases, as well as their immense healthcare cost burden.

“We are impressed by the potential of NRG’s small molecules as orally-bioavailable and brain-penetrant treatments and look forward to working with the team to move the programs through IND-enabling studies. If successful, the company’s mitochondrial therapeutics could transform the lives of patients suffering from Parkinson’s and other neurodegenerative diseases.”

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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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