̽��ֱ�� of Cambridge - Rosetrees Trust

Autistic individuals have increased risk of chronic physical health conditions across the whole body

Anonymous — Fri, 29 Sep 2023 12:38:16 +0000

Previous studies have shown that autistic people are dying far younger than others and that they are more likely to experience a range of physical health conditions. Until now, it was believed that autistic people were more likely to have specific conditions, such as gastrointestinal pain, sleep problems, and epilepsy/seizure disorders.

̽��ֱ��new study is different in that it investigated a much wider range of health risks than has been done before and shows that autistic people experience a much broader range of health vulnerabilities than was previously thought.

Specifically, autistic people are more likely to have physical health conditions across all organ systems, including the brain (such as migraine), the gastrointestinal system (for example coeliac disease), and the endocrine system (for example endometriosis), compared to non-autistic people.

Dr Elizabeth Weir, a Research Associate at the Autism Research Centre in Cambridge, who led the team, said: “This study emphasizes the increased health vulnerability of autistic people both in the types and number of conditions they may have. We now need to understand the causes of these increased risks, which are likely multifactorial in nature.”

This is the first study to show that autistic people are more likely than non-autistic people to experience ‘physical health multimorbidity’, meaning that they have at least two or more physical health conditions. These include co-occurring fibromyalgia (which causes chronic pain throughout the body) and polycystic ovarian syndrome (which causes irregular menstrual cycles, infertility, excess hair growth, and acne in women) across different organ systems.

̽��ֱ��study was conducted by a team at the ARC and used an anonymized, self-report survey to compare the experiences of 1,129 autistic people with 1,176 non-autistic people aged 16-90 years. ̽��ֱ��participants were international, although 67% of participants were from the UK.

̽��ֱ��survey assessed risk of 60 physical health conditions across nine different organ systems (gastrointestinal, endocrine, rheumatological, neurological, ocular, renal/hepatic, otolaryngological, haematological, and dermatological). ̽��ֱ��analysis took into account other factors such as age, sex assigned at birth, country of residence, ethnicity, education-level, alcohol use, smoking, body mass index, and family medical history.

̽��ֱ��team found that autistic people were more likely to have diagnosed medical conditions across all nine organ systems tested, compared to non-autistic people. Regarding specific conditions, autistic people had higher rates of 33 specific conditions compared to non-autistic peers. These included coeliac disease, gallbladder disease, endometriosis, syncope (fainting or passing out), vertigo, urinary incontinence, eczema, and iron deficiency anaemia.

Dr John Ward, a visiting research scientist at the ARC in Cambridge, who conducted the analysis, said: “This research adds to the body of evidence that the healthcare needs of autistic people are greater than those of non-autistic people. More research is required, particularly surrounding the early identification, and monitoring of chronic conditions.”

This is also the first epidemiological study to show that Ehlers-Danlos Syndrome (EDS) – a group of disorders that affects connective tissues and which cause symptoms such as joint hypermobility, loose joints that dislocate easily, joint pain and clicking joints, skin that bruises easily, extreme tiredness, digestive problems, dizziness, stretchy skin, wounds that are slow to heal, organ prolapse, and hernias – may be more common among autistic women than non-autistic women.

̽��ֱ��new research also replicates previous findings to show that autistic people have higher rates of all central sensitivity syndromes, which are a varied group of conditions that are related to dysregulation of the central nervous system, compared to non-autistic people. Central sensitivity syndromes include irritable bowel syndrome (IBS), temporomandibular joint syndrome (TMJ), migraine, tinnitus, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and fibromyalgia.

̽��ֱ��new study also investigated risks of physical health multimorbidity with a novel application of ‘network analysis’, a technique used to understand relationships between different parts of a system. This analysis method is regularly used in neuroscience to understand how different regions of the brain interact with each other. In this study, the analysis assessed how often conditions from different organ systems occurred together in the same person. In addition to highlighting complex health needs, this analysis established for the first time that the combinations of medical conditions that frequently co-occur may be different between autistic and non-autistic adults.

These results are preliminary evidence that healthcare providers such as GPs or family physicians need to be monitoring the health care needs of autistic people much more closely.

Dr Carrie Allison, Director of Strategy at the ARC and a member of the team, added: “These findings highlight the acute need to adapt the healthcare system to better meet the needs of autistic people. These results must be confirmed in larger, population-based samples.”

Professor Sir Simon Baron-Cohen, Director of the ARC and another member of the team, said: “We are aware of the risks of mental health conditions in autistic people, but this new research identifies their risks of physical health conditions too. We need to urgently re-evaluate current health care systems to improve support for autistic people.”

Funding for this project was provided by the Autism Centre of Excellence at Cambridge, the Rosetrees Trust, the Cambridge and Peterborough NHS Foundation Trust, the Corbin Charitable Trust, the Queen Anne’s Gate Foundation, the MRC, the Wellcome Trust and the Innovative Medicines Initiative.

Reference

Ward, J & Weir, E, Allison, C, Baron-Cohen, S. Increased rates of chronic physical health conditions across all organ systems in autistic adolescents and adults. Molecular Autism (2023).

Autistic people have higher rates of chronic physical health conditions across the whole body and are more likely to have complex health needs, according to a study led by researchers at the ̽��ֱ�� of Cambridge. Their findings, published in the journal Molecular Autism, have important implications for the clinical care of autistic people.

This study emphasizes the increased health vulnerability of autistic people both in the types and number of conditions they may have

Elizabeth Weir

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Two autistic friends sitting outside using stim toys and laughing at their phones

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Autistic individuals have poorer health and healthcare

Anonymous — Fri, 27 May 2022 07:52:21 +0000

These findings, published in Molecular Autism, have important implications for the healthcare and support of autistic individuals.

Many studies indicate that autistic people are dying far younger than others, but there is a paucity of research on the health and healthcare of autistic people across the adult lifespan. While some studies have previously suggested that autistic people may have significant barriers to accessing healthcare, only a few, small studies have compared the healthcare experiences of autistic people to others.

In the largest study to date on this topic, the team at the Autism Research Centre (ARC) in Cambridge used an anonymous, self-report survey to compare the experiences of 1,285 autistic individuals to 1,364 non-autistic individuals, aged 16-96 years, from 79 different countries. 54% of participants were from the UK. ̽��ֱ��survey assessed rates of mental and physical health conditions, and the quality of healthcare experiences.

̽��ֱ��team found that autistic people self-reported lower quality healthcare than others across 50 out of 51 items on the survey. Autistic people were far less likely to say that they could describe how their symptoms feel in their body, describe how bad their pain feels, explain what their symptoms are, and understand what their healthcare professional means when they discuss their health. Autistic people were also less likely to know what is expected of them when they go to see their healthcare professional, and to feel they are provided with appropriate support after receiving a diagnosis, of any kind.

Autistic people were over seven times more likely to report that their senses frequently overwhelm them so that they have trouble focusing on conversations with healthcare professionals. In addition, they were over three times more likely to say they frequently leave their healthcare professional’s office feeling as though they did not receive any help at all. Autistic people were also four times more likely to report experiencing shutdowns or meltdowns due to a common healthcare scenario (e.g., setting up an appointment to see a healthcare professional).

̽��ֱ��team then created an overall ‘health inequality score’ and employed novel data analytic methods, including machine learning. Differences in healthcare experiences were stark: the models could predict whether or not a participant was autistic with 72% accuracy based only on their ‘health inequality score’. ̽��ֱ��study also found worryingly high rates of chronic physical and mental health conditions, including arthritis, breathing concerns, neurological conditions, anorexia, anxiety, ADHD, bipolar disorder, depression, insomnia, OCD, panic disorders, personality disorders, PTSD, SAD, and self-harm.

Dr Elizabeth Weir, a postdoctoral scientist at the ARC in Cambridge, and the lead researcher of the study, said: “This study should sound the alarm to healthcare professionals that their autistic patients are experiencing high rates of chronic conditions alongside difficulties with accessing healthcare. Current healthcare systems are failing to meet very fundamental needs of autistic people.”

Dr Carrie Allison, Director of Strategy at the ARC and another member of the team, added: “Healthcare systems must adapt to provide appropriate reasonable adjustments to autistic and all neurodiverse patients to ensure that they have equal access to high quality healthcare.”

Professor Sir Simon Baron-Cohen, Director of the ARC and a member of the team, said: “This study is an important step forward in understanding the issues that autistic adults are facing in relation to their health and health care, but much more research is needed. We need more research on long term outcomes of autistic people and how their health and healthcare can be improved. Clinical service providers need to ask autistic people what they need and then meet these needs.”

̽��ֱ��research was funded by the Autism Centre of Excellence, the Rosetrees Trust, the Cambridge and Peterborough NHS Foundation Trust, the Corbin Charitable Trust, the Queen Anne’s Gate Foundation, the MRC, the Wellcome Trust and the Innovative Medicines Initiative.

Reference
Weir, E, Allison, C, & Baron-Cohen, S. Autistic adults have poorer quality healthcare and worse health based on self-report data. Molecular Autism (2022).

Autistic individuals are more likely to have chronic mental and physical health conditions, suggests new research from the ̽��ֱ�� of Cambridge. Autistic individuals also report lower quality healthcare than others.

This study should sound the alarm to healthcare professionals that their autistic patients are experiencing high rates of chronic conditions alongside difficulties with accessing healthcare

Elizabeth Weir

NicolasMcComber

Autistic trans man at home looking out of a window

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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Lab-grown beating heart cells identify potential drug to prevent COVID-19-related heart damage

cjb250 — Thu, 05 Aug 2021 08:35:20 +0000

̽��ֱ��heart is one the major organs damaged by infection with SARS-CoV-2, particularly the heart cells, or ‘cardiomyocytes’, which contract and circulate blood. It is also thought that damage to heart cells may contribute to the symptoms of long COVID.

Patients with underlying heart problems are more than four times as likely to die from COVID-19, the disease caused by SARS-CoV-2 infection. ̽��ֱ��case fatality rate in patients with COVID-19 rises from 2.3% to 10.5% in these individuals.

To gain entry into our cells, SARS-CoV-2 hijacks a protein on the surface of the cells, a receptor known as ACE2. Spike proteins on the surface of SARS-CoV-2 – which give it its characteristic ‘corona’-like appearance – bind to ACE2. Both the spike protein and ACE2 are then cleaved, allowing genetic material from the virus to enter the host cell. ̽��ֱ��virus manipulates the host cell’s machinery to allow itself to replicate and spread.

A team of scientists at the ̽��ֱ�� of Cambridge has used human embryonic stem cells to grow clusters of heart cells in the lab and shown that these cells mimic the behaviour of the cells in the body, beating as if to pump blood. Crucially, these model heart cells also contained the key components necessary for SARS-CoV-2 infection – in particular, the ACE2 receptor.

Working in special biosafety laboratories and using a safer, modified synthetic (‘pseudotyped’) virus decorated with the SARS-CoV-2 spike protein, the team mimicked how the virus infects the heart cells. They then used this model to screen for potential drugs to block infection.

Dr Sanjay Sinha from the Wellcome-MRC Cambridge Stem Cell Institute said: “Using stem cells, we’ve managed to create a model which, in many ways, behaves just like a heart does, beating in rhythm. This has allowed us to look at how the coronavirus infects cells and, importantly, helps us screen possible drugs that might prevent damage to the heart.”

̽��ֱ��team showed that some drugs that targeted the proteins involved in SARS-CoV-2 viral entry signiﬁcantly reduced levels of infection. These included an ACE2 antibody that has been shown previously to neutralise pseudotyped SARS-CoV-2 virus, and DX600, an experimental drug.

DX600 is an ACE2 peptide antagonist – that is, a molecule that specifically targets ACE2 and inhibits the activity of peptides that play a role in allowing the virus to break into the cell.

DX600 was around seven times more effective at preventing infection compared to the antibody, though the researchers say this may be because it was used in higher concentrations. ̽��ֱ��drug did not affect the number of heart cells, implying that it would be unlikely to be toxic.

Professor Anthony Davenport from the Department of Medicine and a fellow at St Catharine’s College, Cambridge said: “ ̽��ֱ��spike protein is like a key that fits into the ‘lock’ on the surface of the cells – the ACE2 receptor – allowing it entry. DX600 acts like gum, jamming the lock’s mechanism, making it much more difficult for the key to turn and unlock the cell door.

“We need to do further research on this drug, but it could provide us with a new treatment to help reduce harm to the heart in patients recently infected with the virus, particularly those who already have underlying heart conditions or who have not been vaccinated. We believe it may also help reduce the symptoms of long COVID.”

̽��ֱ��research was largely supported by Wellcome, Addenbrooke’s Charitable Trust, Rosetrees Trust Charity and British Heart Foundation.

Reference
Williams, TL et al. Human embryonic stem cell-derived cardiomyocyte platform screens inhibitors of SARS-CoV-2 infection. Communications Biology; 29 Jul 2021; DOI: 10.1038/s42003-021-02453-y

Cambridge scientists have grown beating heart cells in the lab and shown how they are vulnerable to SARS-CoV-2 infection. In a study published in Communications Biology, they used this system to show that an experimental peptide drug called DX600 can prevent the virus entering the heart cells.

Using stem cells, we’ve managed to create a model which, in many ways, behaves just like a heart does, beating in rhythm. This has allowed us to look at how the coronavirus infects cells and, importantly, helps us screen possible drugs that might prevent damage to the heart

Sanjay Sinha

Beating heart cells infected with virus

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Heart

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Autistic individuals may be more likely to use recreational drugs to self-medicate their mental health

cjb250 — Thu, 01 Jul 2021 22:30:48 +0000

There is significant debate about substance use of autistic adolescents and adults. Some studies indicate that autistic individuals are less likely to use substances, whereas others suggest that autistic individuals are at greater risk of substance misuse or abuse. ̽��ֱ��team at the Autism Research Centre in Cambridge used a ‘mixed methods’ design to consider both the frequency of substance use among autistic individuals, as well as their self-reported experiences of substance use.

Overall, 1,183 autistic and 1,203 non-autistic adolescents and adults (aged 16-90 years) provided information about the frequency of their substance use via an anonymous, online survey; of this group, 919 individuals also gave more in-depth responses about their experiences of substance use.

Autistic adults were less likely than non-autistic peers to use substances. Only 16% of autistic adults, compared to 22% of non-autistic adults, reported drinking on three or more days per week on average. Similarly, only 4% of autistic adults reported binge-drinking compared to 8% of non-autistic adults.

There were also some sex differences in patterns of substance use: autistic males were less likely than non-autistic males to report ever having smoked or used drugs. In contrast, the team did not find differences in the patterns of frequency of smoking or drug use between autistic and non-autistic females.

However, despite lower rates of substance use overall, the qualitative findings of the study provide a much less hopeful picture: autistic adults were nearly nine times more likely than non-autistic peers to report using recreational drugs (such as marijuana, cocaine and amphetamines) to manage unwanted symptoms, including autism-related symptoms.

Drugs were used to reduce sensory overload, help with mental focus, and provide routine, among other reasons. Several autistic participants also indirectly referenced using substances to mask their autism. Past research has shown that this behavioural management (also known as ‘camouflaging’ or ‘compensating’) has been linked to emotional exhaustion, worse mental health, and even increased risk of suicide among autistic adults.

Autistic adolescents and adults were also over three times more likely than others to report using substances to manage mental health symptoms, including anxiety, depression, and suicidal thoughts. Several participants specifically noted that they used drugs for self-medication. However, this self-medication was not always viewed as negative by participants, and several noted that using recreational drugs allowed them to reduce the doses of prescribed medications for mental health conditions, which was a welcome change due to the sometimes significant side effects from their prescribed medications.

Another area of concern was the strong association between vulnerability and substance use among autistic teenagers and adults. Previous work from the Cambridge team suggests that autistic adults may be much more likely to have adverse life experiences and be at greater risk of suicide than others. ̽��ֱ��findings of the new study indicate that autistic individuals are over four times more likely to report vulnerability associated with substance use compared to their non-autistic peers, including dependence/addiction, using drugs to deal with past trauma, and substance use associated with suicide.

In addition, the study identified two new areas of vulnerability not been previously reported: being forced, tricked, or accidentally taking drugs; and childhood use of substances (at the age of 12 years or younger).

Elizabeth Weir, a PhD student at the Autism Research Centre in Cambridge, and the lead researcher of the study, said: “Whether or not the substances currently classed as ‘recreational’ could be used medically remains an open question. It is evident that the current systems of health and social care support are not meeting the needs of many autistic teenagers and adults.

“No one should feel that they need to self-medicate for these issues without guidance from a healthcare professional. Identifying new forms of effective support is urgent considering the complex associations between substance use, mental health, and behaviour management—particularly as camouflaging and compensating behaviours are associated with suicide risk among autistic individuals.”

Dr Carrie Allison, Director of Research Strategy at the Autism Research Centre and a member of the research team, said: “While some of our results suggest lower likelihood of substance use overall, physicians should not assume that their autistic patients aren’t using drugs. Drug use can be harmful so healthcare providers should aim to establish trusting relationships with autistic and non-autistic patients alike to foster frank and honest conversations about substance use.”

Professor Simon Baron-Cohen, Director of the Autism Research Centre and a member of the team, said: “We continue to see new areas in which autistic adults experience vulnerability: mental health, physical health, suicide risk, lifestyle patterns, the criminal justice system, and so on. Substance use is now another area that we need to consider when developing new forms of support for autistic individuals. It is essential that we ensure that autistic people have equal access to high quality social and healthcare that can appropriately support their specific needs; and, unfortunately, it seems clear that our current systems are still not meeting this mark.”

̽��ֱ��research was funded by the Autism Research Trust, Rosetrees Trust, Cambridge and Peterborough NHS Foundation Trust, Corbin Charitable Trust, Medical Research Council, Wellcome and the Innovative Medicines Initiative.

Reference
Weir, E, Allison, C, & Baron-Cohen, S. Understanding the substance use of autistic adolescents and adults: a mixed methods approach. ̽��ֱ��Lancet Psychiatry (2021).

While autistic individuals are less likely to use substances, those who do so are more likely to self-medicate for their mental health symptoms, according to new research from the ̽��ֱ�� of Cambridge and published today in ̽��ֱ��Lancet Psychiatry.

It is essential that we ensure that autistic people have equal access to high quality social and healthcare that can appropriately support their specific needs; and, unfortunately, it seems clear that our current systems are still not meeting this mark

Simon Baron-Cohen

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Unhealthy patterns of diet, exercise, and sleep linked to high risk of cardiovascular disease in autistic people

cjb250 — Mon, 10 May 2021 15:34:45 +0000

̽��ֱ��results are published today in the journal Molecular Autism.

Earlier research suggests that autistic people die 16-35 years younger than expected, and that greater health problems may contribute to this risk. ̽��ֱ��present study is the first to consider the diet, exercise, and sleep patterns of autistic adults and how these patterns may relate to health outcomes.

̽��ֱ��team at the Autism Research Centre in Cambridge developed an anonymous, online survey about lifestyle choices and daily habits, personal medical history, and family medical history. ̽��ֱ��final study included 1,183 autistic adults and 1,203 non-autistic adults aged 16-90 years.

̽��ֱ��results showed that autistic adults were far less likely than non-autistic adults to meet very minimal health recommendations for diet, exercise, and sleep. Autistic adults were also far more likely to have atypical eating patterns (including limited diet) and sleep disturbance. They were more likely to be underweight or obese than non-autistic individuals.

These poor lifestyle habits were associated with greater risk of cardiovascular conditions such as high blood pressure, heart disease, and stroke among autistic males, and this was a stronger association even than a family history of a cardiovascular condition. Though it is not possible to say conclusively that a poorer lifestyle led to cardiovascular problems, the findings provide the first indication that promoting healthy choices regarding diet, exercise, and sleep may help to reduce the excess risks of health conditions in autistic adults.

While the results indicate that there may be other biological or environmental factors that leave autistic individuals at greater risk of health conditions, they also provide a clear target for intervention. Difficulties with maintaining a healthy lifestyle may also have knock-on effects beyond physical health, including limiting opportunities for social interaction (which may centre around mealtimes or exercise), and could contribute to worsening mental health, and affect employment or education.

̽��ֱ��lead researcher of the study, Elizabeth Weir, a PhD student at the Autism Research Centre in Cambridge, said: “These findings help us to better understand the experiences of autistic adults, and have wider implications for quality of life. We need to understand the reasons for restricted diet, limited exercise, and lack of sleep, to provide better support. This may include programmes for health education, and additional mental health support or supported living and working schemes.”

Dr Carrie Allison, Director of Research Strategy at the Autism Research Centre and a member of the research team, said: “ ̽��ֱ��challenges we see among autistic children regarding lifestyle behaviours extend into adulthood. Given the implications for risk of chronic disease and length of life, it is critical that we work to identify effective strategies for supporting health choices by autistic people of all ages.”

Professor Simon Baron-Cohen, Director of the Autism Research Centre and a member of the team, said: “ ̽��ֱ��wider picture suggests that autistic adults experience vulnerability in a variety of contexts, and this is just one new area that we should consider. Seeing that autistic adults are having such a hard time comparatively with healthy lifestyle habits has clear healthcare and policy implications: we need to create new and better support systems tailored to the specific needs of autistic people.”

Reference
Weir, E., et al. An investigation of the diet, exercise, sleep, BMI, and health outcomes of autistic adults. Molecular Autism 12, 31 (2021). DOI: 10.1186/s13229-021-00441-x

Funding
Funding for this project was generously provided by the Autism Research Trust, the Rosetrees Trust, and the Cambridge and Peterborough NHS Foundation Trust, the Corbin Charitable Trust, the MRC, the Wellcome Trust and the Innovative Medicines Initiative.

Autistic people have far greater risks of long term physical health conditions than others, but the reasons for this remain unclear. New research from the ̽��ֱ�� of Cambridge suggests that unhealthy lifestyle habits may be an important contributing factor.

These findings help us to better understand the experiences of autistic adults, and have wider implications for quality of life. We need to understand the reasons for restricted diet, limited exercise, and lack of sleep, to provide better support

Elizabeth Weir

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Autistic adults have a higher rate of physical health conditions

Anonymous — Thu, 10 Sep 2020 15:22:52 +0000

Earlier research has shown that autistic people on average die younger than others and that this may be, in part, due to chronic physical health conditions. Previous studies have also shown that autistic people are at higher risk of a variety of health conditions, but we don’t know what is driving these increased risks. Thus, better understanding of the physical health of autistic adults may help us improve both their quality and length of life.

1,156 autistic individuals and 1,212 non-autistic individuals took part in an anonymous, online survey developed by the team about their lifestyle choices and daily habits, personal and family medical history. ̽��ֱ��results indicate that autistic individuals are, on average, 1.5 to 4.3 times as likely to have a wide variety of health conditions, including low blood pressure, arrhythmias, asthma, and prediabetes.

This new study is also the first to examine the influence of smoking, alcohol use, and BMI. Surprisingly, the results show that these lifestyle factors (which increase the risk of chronic physical health problems in the general population) do not account for the heightened risk of heart, lung, and diabetic conditions seen among autistic adults.

̽��ֱ��study also explored the experiences of female respondents and of older adults, both of whom remain understudied groups. ̽��ֱ��results revealed that autistic females, even more so than autistic males, are more likely to report increased risks of physical health conditions. In addition, the types of conditions of risk depend on the person’s biological sex. For example, autistic females are 4.3 times more likely to have prediabetes than non-autistic females; however, autistic and non-autistic males are equally likely to have prediabetes. These results suggest that a “one size fits all” approach to the healthcare of autistic people may not be effective.

Elizabeth Weir, the PhD student who led the study, said: “This is a first step in better understanding why autistic individuals are so much more likely to have chronic physical health problems. While smoking, alcohol, and BMI may play a role, we now need to focus on what other biological (e.g. genetic, hormonal, etc), environmental, lifestyle (e.g. diet, exercise, sleep, etc) or healthcare-related factors are contributing to these health disparities.”

Professor Simon Baron-Cohen, Director of the Autism Research Centre at Cambridge, who was part of the team, said: “This new study highlights the physical health risks to autistic individuals, and has important implications for their healthcare. Understanding the reasons why these disparities exist will allow us to better support autistic individuals and improve the quality and length of their lives.”

Funding for this project was provided by the Autism Research Trust, the Rosetrees Trust, and the Cambridge and Peterborough NHS Foundation Trust.

Reference
Weir, E at al. Increased prevalence of non-communicable physical health conditions among autistic adults. Autism; 9 Sept 2020; DOI: 10.1177/1362361320953652

Autistic individuals are more likely to have chronic physical health conditions, particularly heart, lung, and diabetic conditions, according to a new study by researchers at the ̽��ֱ�� of Cambridge. ̽��ֱ��results are published in the journal Autism.

This is a first step in better understanding why autistic individuals are so much more likely to have chronic physical health problems

Elizabeth Weir

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Doctor testing blood pressure

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Nature’s epidural: Genetic variant may explain why some women don’t need pain relief during childbirth

cjb250 — Tue, 21 Jul 2020 15:00:21 +0000

Childbirth is widely recognised as a painful experience. However, every woman’s experience of labour and birth is unique, and the level of discomfort and pain experienced during labour varies substantially between women.

A collaboration between clinicians and scientists based at Addenbrooke’s Hospital, part of Cambridge ̽��ֱ�� Hospitals NHS Foundation Trust (CUH), and the ̽��ֱ�� of Cambridge sought to investigate why some mothers report less pain during labour.

A group of women was recruited and characterised by the team led by Dr Michael Lee from the ̽��ֱ��’s Division of Anaesthesia. All the women had carried their first-born to full term and did not request any pain relief during an uncomplicated vaginal delivery. Dr Lee and colleagues carried out a number of tests on the women, including applying heat and pressure to their arms and getting them to plunge their hands into icy water.

Compared to a control group of women that experienced similar births, but were given pain relief, the test group showed higher pain thresholds for heat, cold and mechanical pressure, consistent with them not requesting pain relief during childbirth. ̽��ֱ��researchers found no differences in the emotional and cognitive abilities of either group, suggesting an intrinsic difference in their ability to detect pain.

“It is unusual for women to not request gas and air, or epidural for pain relief during labour, particularly when delivering for the first time,” said Dr Lee, joint first author. “When we tested these women, it was clear their pain threshold was generally much higher than it was for other women.”

Next, senior co-author, Professor Geoff Woods, and his colleagues at the Cambridge Institute for Medical Research sequenced the genetic code of both groups of women and found that those in the test group had a higher-than-expected prevalence of a rare variant of the gene KCNG4. It’s estimated that one approximately 1 in 100 women carry this variant.

KCNG4 provides the code for the production of a protein that forms part of a ‘gate’, controlling the electric signal that flows along our nerve cells. As the joint first author Dr Van Lu showed, sensitivity of this gatekeeper to electric signals that had the ability to open the gate and turn nerves on was reduced by the rare variant.

This was confirmed in a study involving mice led by Dr Ewan St. John Smith from the Department of Pharmacology, who showed that the threshold at which the ‘defective’ gates open, and hence the nerve cell switches ‘on’, is higher – which may explain why women with this rare gene variant experience less pain during childbirth.

Dr St. John Smith, senior co-author, explained: “ ̽��ֱ��genetic variant that we found in women who feel less pain during childbirth leads to a ‘defect’ in the formation of the switch on the nerve cells. In fact, this defect acts like a natural epidural. It means it takes a much greater signal – in other words, stronger contractions during labour – to switch it on. This makes it less likely that pain signals can reach the brain.”

“Not only have we identified a genetic variant in a new player underlying different pain sensitivities,” added senior co-author Professor Frank Reimann, “but we hope this can open avenues to the development of new drugs to manage pain.”

“This approach of studying individuals who show unexpected extremes of pain experience also may find wider application in other contexts, helping us understand how we experience pain and develop new drugs to treat it,” said Professor David Menon, senior co-author.

̽��ֱ��research was support by the Addenbrooke’s Charitable Trust, the National Institute for Health Research Cambridge Biomedical Research Centre, Wellcome, Rosetrees Trust and the BBSRC.

Reference
Lee, M.C. et al (2020). Human labour pain is influenced by the voltage-gated potassium channel Kv6.4 subunit. Cell Reports; 21 July 2020; DOI: 10.1016/j.celrep.2020.107941

Women who do not need pain relief during childbirth may be carriers of a key genetic variant that acts a natural epidural, say scientists at the ̽��ֱ�� of Cambridge. In a study published today in the journal Cell Reports, the researchers explain how the variant limits the ability of nerve cells to send pain signals to the brain.

This [variant] acts like a natural epidural. It means it takes a much greater signal – in other words, stronger contractions during labour – to switch it on. This makes it less likely that pain signals can reach the brain

Ewan St. John Smith

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How to train your drugs: from nanotherapeutics to nanobots

sc604 — Fri, 23 Jun 2017 15:00:56 +0000

Chemotherapy benefits a great many patients but the side effects can be brutal.

When a patient is injected with an anti-cancer drug, the idea is that the molecules will seek out and destroy rogue tumour cells. However, relatively large amounts need to be administered to reach the target in high enough concentrations to be effective. As a result of this high drug concentration, healthy cells may be killed as well as cancer cells, leaving many patients weak, nauseated and vulnerable to infection.

One way that researchers are attempting to improve the safety and efficacy of drugs is to use a relatively new area of research known as nanothrapeutics to target drug delivery just to the cells that need it.

Professor Sir Mark Welland is Head of the Electrical Engineering Division at Cambridge. In recent years, his research has focused on nanotherapeutics, working in collaboration with clinicians and industry to develop better, safer drugs. He and his colleagues don’t design new drugs; instead, they design and build smart packaging for existing drugs.

Nanotherapeutics come in many different configurations, but the easiest way to think about them is as small, benign particles filled with a drug. They can be injected in the same way as a normal drug, and are carried through the bloodstream to the target organ, tissue or cell. At this point, a change in the local environment, such as pH, or the use of light or ultrasound, causes the nanoparticles to release their cargo.

Nano-sized tools are increasingly being looked at for diagnosis, drug delivery and therapy. “There are a huge number of possibilities right now, and probably more to come, which is why there’s been so much interest,” says Welland. Using clever chemistry and engineering at the nanoscale, drugs can be ‘taught’ to behave like a Trojan horse, or to hold their fire until just the right moment, or to recognise the target they’re looking for.

“We always try to use techniques that can be scaled up – we avoid using expensive chemistries or expensive equipment, and we’ve been reasonably successful in that,” he adds. “By keeping costs down and using scalable techniques, we’ve got a far better chance of making a successful treatment for patients.”

In 2014, he and collaborators demonstrated that gold nanoparticles could be used to ‘smuggle’ chemotherapy drugs into cancer cells in glioblastoma multiforme, the most common and aggressive type of brain cancer in adults, which is notoriously difficult to treat. ̽��ֱ��team engineered nanostructures containing gold and cisplatin, a conventional chemotherapy drug. A coating on the particles made them attracted to tumour cells from glioblastoma patients, so that the nanostructures bound and were absorbed into the cancer cells.

Once inside, these nanostructures were exposed to radiotherapy. This caused the gold to release electrons that damaged the cancer cell’s DNA and its overall structure, enhancing the impact of the chemotherapy drug. ̽��ֱ��process was so effective that 20 days later, the cell culture showed no evidence of any revival, suggesting that the tumour cells had been destroyed.

While the technique is still several years away from use in humans, tests have begun in mice. Welland’s group is working with MedImmune, the biologics R&D arm of pharmaceutical company AstraZeneca, to study the stability of drugs and to design ways to deliver them more effectively using nanotechnology.

“One of the great advantages of working with MedImmune is they understand precisely what the requirements are for a drug to be approved. We would shut down lines of research where we thought it was never going to get to the point of approval by the regulators,” says Welland. “It’s important to be pragmatic about it so that only the approaches with the best chance of working in patients are taken forward.”

̽��ֱ��researchers are also targeting diseases like tuberculosis (TB). With funding from the Rosetrees Trust, Welland and postdoctoral researcher Dr Íris da luz Batalha are working with Professor Andres Floto in the Department of Medicine to improve the efficacy of TB drugs.

Their solution has been to design and develop nontoxic, biodegradable polymers that can be ‘fused’ with TB drug molecules. As polymer molecules have a long, chain-like shape, drugs can be attached along the length of the polymer backbone, meaning that very large amounts of the drug can be loaded onto each polymer molecule. ̽��ֱ��polymers are stable in the bloodstream and release the drugs they carry when they reach the target cell. Inside the cell, the pH drops, which causes the polymer to release the drug.

In fact, the polymers worked so well for TB drugs that another of Welland’s postdoctoral researchers, Dr Myriam Ouberaï, has formed a start-up company, Spirea, which is raising funding to develop the polymers for use with oncology drugs. Ouberaï is hoping to establish a collaboration with a pharma company in the next two years.

“Designing these particles, loading them with drugs and making them clever so that they release their cargo in a controlled and precise way: it’s quite a technical challenge,” adds Welland. “ ̽��ֱ��main reason I’m interested in the challenge is I want to see something working in the clinic – I want to see something working in patients.”

Could nanotechnology move beyond therapeutics to a time when nanomachines keep us healthy by patrolling, monitoring and repairing the body?

Nanomachines have long been a dream of scientists and public alike. But working out how to make them move has meant they’ve remained in the realm of science fiction.

But last year, Professor Jeremy Baumberg and colleagues in Cambridge and the ̽��ֱ�� of Bath developed the world’s tiniest engine – just a few billionths of a metre in size. It’s biocompatible, cost-effective to manufacture, fast to respond and energy efficient.

̽��ֱ��forces exerted by these ‘ANTs’ (for ‘actuating nano-transducers’) are nearly a hundred times larger than those for any known device, motor or muscle. To make them, tiny charged particles of gold, bound together with a temperature-responsive polymer gel, are heated with a laser. As the polymer coatings expel water from the gel and collapse, a large amount of elastic energy is stored in a fraction of a second. On cooling, the particles spring apart and release energy.

̽��ֱ��researchers hope to use this ability of ANTs to produce very large forces relative to their weight to develop three-dimensional machines that swim, have pumps that take on fluid to sense the environment and are small enough to move around our bloodstream.

Working with Cambridge Enterprise, the ̽��ֱ��’s commercialisation arm, the team in Cambridge's Nanophotonics Centre hopes to commercialise the technology for microfluidics bio-applications. The work is funded by the Engineering and Physical Sciences Research Council and the European Research Council.

“There’s a revolution happening in personalised healthcare, and for that we need sensors not just on the outside but on the inside,” explains Baumberg, who leads an interdisciplinary Strategic Research Network and Doctoral Training Centre focused on nanoscience and nanotechnology.

“Nanoscience is driving this. We are now building technology that allows us to even imagine these futures.”

Read more about research on future therapeutics in Research Horizons magazine.

Nanotechnology is creating new opportunities for fighting disease – from delivering drugs in smart packaging to nanobots powered by the world’s tiniest engines.

Designing these particles, loading them with drugs and making them clever so that they release their cargo in a controlled and precise way: it’s quite a technical challenge.

Mark Welland

Yu Ji

Artist's impression of a nanobot

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

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