Tag: 25/1/23

A New Wave of Academia Spinouts is Shaking up Drug Development

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In recent times, new drug discoveries by independent large pharmaceutical companies have become increasingly rare, with almost 60% of new drugs discovered through mergers and acquisitions and drug licensing. Fortunately, an emerging trend of spinouts from academia and R&D investments heralds a promising shift in the industry’s interorganisational deal networks to improve research and development in the future. Researchers explore this new trend in Drug Discovery Today.

Launching a new drug in the market is risky, thanks to a low probability of success during the research and development (R&D) phase and the high costs involved. But through an improved understanding of disease biology, decision-making can be more streamlined through the effective use of scientific information.

With this in mind, researchers from Ritsumeikan University, Japan, led by Associate Professor Kota Kodama are uncovering how the trends in interorganisational deals in the pharmaceutical industry are changing to improve R&D productivity and drug discovery. “The network structure of innovation creation in the pharmaceutical industry has changed with the increasing emergence of start-up companies spinning out from academia and research institutions as players in the source of innovation,” explains Dr Kodama.

Their research suggests that the knowledge necessary for breakthrough innovation in drug discovery is more often than not obtained through alliance networks. Over the past decade, large research-based pharmaceutical companies have used research collaborations, innovation incubators, academic centres of excellence, public-private partnerships, mergers and acquisitions (M&As), drug licensing, and corporate venture capital funds as typical methods for external innovation. The researchers now aim to define the changes in the network structure and nature of such alliances that have occurred over the past decade to provide future strategic insights for industry and academic players involved in drug discovery.

Using data from the Cortellis Competitive Intelligence database, the researchers identified nearly 50 000 deals of various kinds related to pharmaceutical R&D across pharmaceutical, digital health software, animal drug, and medical device companies to uncover trends in the creation of new drugs for human use. They also studied the trends of 13 of the largest pharmaceutical companies with annual revenues of more than US$10 billion, who saw an improvement in their CAGR (compound annual growth rate) since 2015. The researchers noticed that the rising CAGR correlated to a significant change in M&A-related deals after 2015, indicating that M&A-related deals drive revenue growth for large pharmaceutical companies.

Furthermore, the number of organisations involved in interorganisational deals has been increasing yearly from 2012 to 2021. Although the number of organisations involved and the number of deals may be increasing, the density of the deal networks is decreasing annually, suggesting that networks are becoming more non-cohesive. The concentration of business relationships between organisations of certain areas in the network changed to dispersion around 2015, and new networks connecting different groups started to form after 2017. These trends are an important illustration of how the industry landscape is gradually evolving away from the traditional network in which large pharmaceutical companies drove drug discovery output. Now, interorganisational deals among more diverse players have become active and are driving R&D productivity for startups in biotechnology and pharmaceuticals.

A clear increase in the number of academia-owned spinouts of advanced technology and expansion of investment in start-ups is a positive sign. The emergence of new chemical modalities, such as biologics, oligonucleotides, and peptides that differ from traditional small molecule drug discovery indicate remarkable changes that have taken place over the past two decades. The trend of increased financing for start-up companies in personalised drug development is beneficial for patent creation and will positively impact innovation creation in the coming years.

“The presence of academia to support the technologies of these start-ups is becoming very important, and government and private support and investment in this area is boosting innovation. Our study shows that such medium- and long-term support may ultimately benefit the health and well-being of humankind,” concludes an optimistic Dr Kodama.

Source: Ritsumeikan University.

Running away from Life’s Stresses: The Phenomenon of Exercise Addiction

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Recreational running offers a lot of physical and mental health benefits – but some people can develop exercise dependence, a form of addiction to physical activity which can cause health issues. Shockingly, signs of exercise dependence are common even in recreational runners. A study published in Frontiers in Psychology investigated whether the concept of escapism can help us understand the relationship between running, well-being, and exercise dependence.

“Escapism is an everyday phenomenon among humans, but little is known regarding its motivational underpinnings, how it affects experiences, and the psychological outcomes from it,” said Dr Frode Stenseng of the Norwegian University of Science and Technology, lead author of the paper.

Running to explore or to evade?

“Escapism is often defined as ‘an activity, a form of entertainment, etc. that helps you avoid or forget unpleasant or boring things.” In other words, many of our everyday activities may be interpreted as escapism,” said Stenseng. “The psychological reward from escapism is reduced self-awareness, less rumination, and a relief from one’s most pressing, or stressing, thoughts and emotions.”

Escapism can restore perspective, or it can act as a distraction from problems that need to be tackled. Escapism which is adaptive, seeking out positive experiences, is referred to as self-expansion. Meanwhile maladaptive escapism, avoiding negative experiences, is called self-suppression. Effectively, running as exploration or as evasion.

“These two forms of escapism are stemming from two different mindsets, to promote a positive mood, or prevent a negative mood,” said Stenseng.

Escapist activities used for self-expansion have more positive effects but also more long-term benefits. Self-suppression, by contrast, tends to suppress positive feelings as well as negative ones and lead to avoidance.

Self-suppression associated with exercise dependence

The team recruited 227 recreational runners, half men and half women, with widely varying running practices. They were asked to fill out questionnaires which investigated three different aspects of escapism and exercise dependence: an escapism scale which measured preference for self-expansion or self-suppression, an exercise dependence scale, and a satisfaction with life scale designed to measure the participants’ subjective well-being.

The scientists found that there was very little overlap between runners who favoured self-expansion and runners who preferred self-suppression modes of escapism. Self-expansion was positively related with well-being, while self-suppression was negatively related to well-being. Self-suppression and self-expansion were both linked to exercise dependence, but self-suppression was much more strongly linked to it. Neither escapism mode was linked to age, gender, or amount of time a person spent running, but both affected the relationship between well-being and exercise dependence. Whether or not a person fulfilled criteria for exercise dependence, a preference for self-expansion would still be linked to a more positive sense of their own well-being.

Although exercise dependence corrodes the potential well-being gains from exercise, it seems that perceiving lower well-being may be both a cause and an outcome of exercise dependency: the dependency might be driven by lower well-being as well as promoting it.

Similarly, experiencing positive self-expansion might be a psychological motive that promotes exercise dependence.

“More studies using longitudinal research designs are necessary to unravel more of the motivational dynamics and outcomes in escapism,” said Stenseng. “But these findings may enlighten people in understanding their own motivation, and be used for therapeutic reasons for individuals striving with a maladaptive engagement in their activity.”

Source: Frontiers

Not all Memories Lost to Sleep Deprivation are Gone Forever

Sleeping man
Photo by Mert Kahveci on Unsplash

Sleep deprivation is bad for memorisation, something which still doesn’t deter many med students from late night cramming. Researchers however have discovered that memories learned during sleep deprivation is not necessarily lost, it is just difficult to recall. Publishing in the journal Current Biology, the researchers have found a way to make this ‘hidden knowledge’ accessible again days after studying whilst sleep-deprived using optogenetic approaches and the asthma drug roflumilast.

University of Groningen neuroscientist Robbert Havekes and his team have extensively studied how sleep deprivation affects memory processes. “We previously focused on finding ways to support memory processes during a sleep deprivation episode,” says Havekes. However, in his latest study, his team examined whether amnesia as a result of sleep deprivation was a direct result of information loss, or merely caused by difficulties retrieving information. “Sleep deprivation undermines memory processes, but every student knows that an answer that eluded them during the exam might pop up hours afterwards. In that case, the information was, in fact, stored in the brain, but just difficult to retrieve.”

Priming the hippocampus

To find out, the researchers selectively introduced optogenetic proteins into neurons that are activated during a learning experience, enabling recall of a specific experience by shining a light on the cells. “In our sleep deprivation studies, we applied this approach to neurons in the hippocampus, the area in the brain where spatial information and factual knowledge are stored,” says Havekes.

First, the genetically engineered mice were given a spatial learning task in which they had to learn the location of individual objects, a process heavily reliant on neurons in the hippocampus. The mice then had to perform this same task days later, but this time with one object moved to a new location. The mice that were deprived of sleep for a few hours before the first session failed to detect this spatial change, which suggests that they cannot recall the original object locations. “However, when we reintroduced them to the task after reactivating the hippocampal neurons that initially stored this information with light, they did successfully remember the original locations,” says Havekes. “This shows that the information was stored in the hippocampus during sleep deprivation, but couldn’t be retrieved without the stimulation.”

Memory problems

The molecular pathway set off during the reactivation is also targeted by the drug roflumilast, which is used by patients with asthma or COPD. Havekes says: “When we gave mice that were trained while being sleep deprived roflumilast just before the second test, they remembered, exactly as happened with the direct stimulation of the neurons.” Since roflumilast is approved for use in humans and can enter the brain, this may lead to testing to see if it can recover ‘lost’ memories for humans..

It might be possible to stimulate the memory accessibility in people with age-induced memory problems or early-stage Alzheimer’s disease with roflumilast,” says Havekes. “And maybe we could reactivate specific memories to make them permanently retrievable again, as we successfully did in mice.” If a subject’s neurons are stimulated with the drug while they try and ‘relive’ a memory, or revise information for an exam, this information might be reconsolidated more firmly in the brain. “For now, this is all speculation of course, but time will tell.”

Source: University of Groningen.

Common Hypertension Drug Extends Lifespan in Animal Studies

Old man
Photo by Kindel Media on Pexels

Researchers have found that, in animal studies, the hypertension drug rilmenidine can extend lifespan and slow ageing. Published in Aging Cell, the findings show that animals treated with rilmenidine at young and older ages increases lifespan and improves health markers by mimicking the effects of caloric restriction.

They also demonstrate that the healthspan and lifespan benefits of rilmenidine treatment in the roundworm C. elegans are mediated by the I1-imidazoline receptor nish-1, identifying this receptor as a potential longevity target.

With side-effects being rare and non-severe, unlike other drugs previously studied for this purpose by the researchers, the widely-prescribed antihypertensive has potential for future translatability.

A caloric restriction diet has thus far proved to be the most robust anti-ageing intervention, promoting longevity across species. However, studies of caloric restriction in humans have had mixed results and side effects, meaning finding medications like rilmenidine that can mimic the benefits of caloric restriction is the most reasonable anti-ageing strategy.

Professor João Pedro Magalhães, who led the research whilst at the University of Liverpool and is now based at the University of Birmingham, said: “With a global ageing population, the benefits of delaying ageing, even if slightly, are immense. Repurposing drugs capable of extending lifespan and healthspan has a huge untapped potential in translational geroscience. For the first time, we have been able to show in animals that rilmenidine can increase lifespan. We are now keen to explore if rilmenidine may have other clinical applications.”

Source: University of Liverpool

Health Care Integration Sees Ballooning Costs for Minor Care Benefit

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Over the past few decades, health care integration has absorbed physician practices and hospitals into large health systems, a practice which was heralded as the way to cut health care costs and boosting quality of care.

But integrated health systems appear to be failing on both fronts, according to the results of a new US study published in JAMA. For patients in health systems, care is only marginally improved while costs are significantly higher compared to those at independent practices or hospitals.

In the US, health systems have grown exponentially in size and market share through mergers and acquisitions of physician practices and hospitals and the joining of separate health systems.

Proponents of consolidation have argued over the years that physicians and hospitals working together in integrated, coordinated systems provide better patients care while being more efficient than independent physician practices and hospitals. This would drive quality of care up while keeping spending steady and even driving costs down.

“One of the key arguments for hospital mergers and practice acquisition was that health systems would deliver better-value care for patients. This study provides the most comprehensive evidence yet that this isn’t happening,” said study first author Nancy Beaulieu at Harvard Medical School.

Today, these systems are responsible for a large proportion of the medical care delivered in the US, some employing thousands of physicians. But despite their impact on population health and the economy, little is known about the actual performance of integrated health organisations, the study authors noted.

A lack of detailed data on performance and scale is a key obstacle. The current analysis is believed to be the first comprehensive national study to compare outcomes between patients receiving care within health systems and outside of them, including patients with private insurance as well as traditional Medicare, which is the US health insurance system for those over 65 or which certain disabilities or conditions. 

The analysis included a total of 580 health systems, accounting 40% of physicians and 84% of general acute care hospital beds. Academic and large nonprofit systems accounted for a majority of system physicians (80%) and system hospital beds (64%).

System hospitals were larger than hospitals than nonsystem ones, with 67% of system hospitals having more than 100 beds, while only 23% of nonsystem hospitals having more than 100 beds. System physician practices were also more likely to have more than 100 physicians compared with nonsystem practices (74% vs 12%). Integrated systems delivered primary care to 41% of traditional Medicare beneficiaries.

As for quality and cost of care delivered within systems, patients with primary care physicians in health systems reported slightly better satisfaction and overall care experience than patients of independent physicians.

This is the case even though many patients with nonsystem primary care providers also receive some of their care in hospitals or specialist practices that are part of a health system. However, care in systems came at a much higher price, contributing to higher overall spending on health care, the research showed.

Prices for services from physicians and hospitals within health systems were significantly higher than for independent healthcare, the study found. Physician services delivered within health systems cost between 12% and 26% more, compared with independent practices. System-based hospital services cost an average of 31% more than care delivered by independent hospitals.

Small differences in quality combined with large differences in cost of care suggests that health systems have not, on average, realised their potential for better care at equal or lower cost, the researchers said.

Members of the research team have compiled a database from various sources to help characterise these health systems and to link claims data with information on health care providers in and out of health systems. The database, housed at NEBR, will be made available for free to other researchers in the near future.

“There’s no question that large, sophisticated health systems have benefits over independent systems,” said study author David Cutler, Harvard economic professor. “Big systems tend to be less vulnerable to economic downturns and they can provide specialised care that would be difficult to maintain in smaller systems. But the hoped-for cost savings benefits of integrated health systems have not yet materialised.”

Source: Harvard Medical School