Author: patienttalk

Posted on Multiple Sclerosis

Trial shows myelin repair in humans is possible

Myelin Sheath
Myelin Sheath


The results from our Phase 2a clinical trial have shown that bexarotene is capable of regenerating lost myelin – the protective coating that surrounds nerve fibres, which is damaged in MS. Now, a new trial of the diabetes drug metformin will build on this work.

Critical to stopping MS

New research presented at the MSVirtual2020 conference has shown that bexarotene, a drug developed to treat cancer, is able to repair myelin in people with relapsing MS. This is a breakthrough that scientists say is critical to their goal of stopping MS.

Professor Alasdair Coles from the University of Cambridge, who led the research, said: “The lessons we’ve learned are incredibly exciting, as we now have further concrete evidence that remyelination in humans is possible. This discovery gives us confidence that we will stop MS, and will swiftly be taken forward into further studies trialling other potential new myelin repair treatments.”

Important lessons learned

In the trial, vision tests and some types of MRI scans showed that bexarotene could repair myelin.

Participants in the trial did experience some serious side effects, including an underactive thyroid gland and high levels of fats in the blood. This means bexarotene won’t be taken forward into a Phase 3 study.

But the lessons we’ve learned from this trial will now be taken forward into new clinical trials.

Co-investigator Professor Siddharthan Chandran from the University of Edinburgh added: “We now understand much more about myelin repair and are in a significantly better position to measure remyelination in clinical trials. While this work was taking place, further lab research identified new and more tolerable treatments that could repair myelin, and we look forward to these being tested in trials imminently.”

A new trial for myelin repair

Promising results from laboratory studies in October 2019 showed the common diabetes drug metformin could repair myelin in rats. We’re proud to announce we’re funding a new Phase 2 clinical trial to test metformin in combination with clemastine (an antihistamine). 50 people with relapsing MS will take part.

It’s hoped that together these treatments will be safe and effective at repairing myelin in people living with MS, and could provide a way to prevent disability progression in the condition.

This new clinical trial will be led by Professor Alasdair Coles. It will build on our current understanding of myelin repair, which has been furthered by the bexarotene clinical trial and the work of Professor Robin Franklin and his team at the MS Society Cambridge Centre for Myelin Repair. In studies in rats, they discovered that metformin was able to mimic the effects of fasting and return cells to a “more youthful state”, and encourage the re-growth of myelin.

Professor Robin Franklin said: “Metformin is one of the most exciting developments in myelin repair we have ever seen. Our findings last year shed light on why cells lose their ability to regenerate myelin, and how this process might be reversed. We’re very proud to have done this work and thrilled to see our discovery taken forward so quickly.”

A major milestone in our plan to stop MS

By 2025 we plan to be in the final stages of testing a range of treatments for everyone with MS.

Dr Emma Gray, our Assistant Director of Research, said: “Finding treatments to stop MS progression is our number one priority, and to do that we need ways to protect nerves from damage and repair lost myelin. This new research is a major milestone in our plan to stop MS and we’re incredibly excited about the potential it’s shown for future studies. We look forward to what comes next.”

Posted on Autism

Genetic variants for autism linked to higher rates of self-harm and childhood maltreatment

Man standing in front of window

People with a higher genetic likelihood of autism are more likely to report higher childhood maltreatment, self-harm and suicidal thoughts according to a new study by researchers at the University of Cambridge. A better understanding of these issues is critical to improving wellbeing in autistic people. The results are published today in Molecular Psychiatry.

Our work highlighting unacceptably high rates of suicide in autistic people was published 5 years ago, yet almost no new support has been provided. Governments need to provide far greater support for autistic individuals and for those with a high number of autistic traitsSimon Baron Cohen

Previous studies by the Cambridge team established that autistic individuals experience higher levels of self-harm, including suicidal thoughts and feelings, and higher rates of childhood maltreatment. This new study shows that the findings hold true even for those with a higher genetic likelihood of autism rather than a formal diagnosis.

The team calculated the genetic likelihood for autism in 100,000 individuals from the UK Biobank Study who had their DNA analysed and who had also provided self-reported information about childhood maltreatment, suicidal ideation, and self-harm. They found that individuals with higher number of genetic variants associated with autism are more likely to report childhood maltreatment, self-harm and suicidal ideation. Those with the highest genetic predisposition to autism on average have a 28% increase in childhood maltreatment, and a 33% increase in self-harm and suicidal ideation, compared to those with the lowest genetic predisposition to autism.

Dr Varun Warrier, who led the study, said: “While we have found an association between a genetic likelihood for autism and adverse life events, we cannot conclude the former causes the latter. We suspect this association reflects that genes partly influence how many autistic traits you have, and some autistic traits such as difficulties in social understanding may lead to a person to be vulnerable to maltreatment. This research highlights the risks of such adverse outcomes for those with a high number of autistic traits, if adequate safe-guarding and support aren’t provided.”

Professor Simon Baron-Cohen, Director of the Autism Research Centre at Cambridge, said: “This new study extends our earlier work by showing that individuals who carry more of the genes associated with autism have higher risks for maltreatment and self-harm. Our work highlighting unacceptably high rates of suicide in autistic people was published 5 years ago, yet almost no new support has been provided. Governments need to provide far greater support for autistic individuals and for those with a high number of autistic traits.”

He added: “Autistic individuals may need a variety of interventions – there’s no ‘one size fits all’ – and these may include an individual support worker, a mentor, opportunities to build social and communication skills and self confidence through activities that the person enjoys, peer support groups, and supported employment schemes. Schools may also need to increase safe-guarding given the risks of victimisation.”

This study was supported by the Autism Research Trust, the Medical Research Council, Wellcome, and the Templeton World Charity Foundation., Inc. It was conducted in association with the NIHR CLAHRC for Cambridgeshire and Peterborough NHS Foundation Trust, and the NIHR Cambridge Biomedical Research Centre.

Posted on Autism

New employment toolkit launched to support autistic young people

employment-toolkit

A new toolkit has been launched to support disadvantaged autistic young people into the job market, following the coronavirus pandemic.


 

The charities Ambitious about Autism and The Autism Education Trust have created the Transition to employment toolkit to tackle the problem of autistic young people falling out of education, employment or training when they leave school.  

The latest Office of National Statistics research shows that over 700,000 young people are currently not in employment, education or training. Autistic job seekers are among the most disadvantaged, with just 22% of people with autism in full-time paid employment, the lowest of all disabled groups.  

Autism, which is often described as a ‘hidden’ disability, affects the way a person communicates and experiences the world around them. Lack of understanding about differences in how autistic people process information and their sensory environment can impact on their ability to thrive in education and employment. For example, in an office environment, too much bright light, or verbal rather than written instructions could be overwhelming for an autistic person.  

The Transition to employment toolkit has been developed to support those working with autistic young people to understand their needs and help them onto the job ladder, or into further training or education. It includes resources for employers, careers professionals and young autistic people themselves.  

The toolkit has templates to help careers professionals understand young people’s skills, experience, career goals and ambitions, tips to help young people prepare for job interviews and information to support employers working with autistic young people. All the resources are free to download, edit and adapt from Ambitious about Autism’s website.  

Jolanta Lasota, Chief Executive of Ambitious about Autism, said:   

“All young people have hopes and aspirations for the future, but for too many autistic young people, these ambitions end when they finish school.  

“This isn’t because autistic young people don’t want to continue in education, training or further study – but because the support they need to thrive in these environments is often non-existent.  

“The coronavirus pandemic is hitting young people hardest, and vulnerable autistic young people are most at risk. It’s crucial we act now to tackle the underlying problems preventing them from reaching their potential.  

“Our new toolkit empowers professionals and employers working with autistic young people to identify their individual needs and create environments in which they can thrive. It also provides advice and support for young people themselves as they prepare to take the next stage in their journey into adulthood.” 

Sarah Broadhurst, Director of the Autism Education Trust, said:  

“As the number of children diagnosed with autism is rising, the number of autistic young people entering the job market is increasing, too. They are full of aspirations and have big plans for the future, as all young people do, but very often encounter difficulties during their first steps into employment because recruitment processes are not catering for their different skills and needs.  

“This fantastic new resource gives practical help and tools to employers, post-16 professionals and young people for every step of the way from preparing an employee profile all the way to post-placement evaluation. Thankfully, more and more employers are recognising the benefits of the diverse and unique talents autistic young people can offer. 

“We hope this document will help them support many more autistic young people to fulfill their aspirations.” 

Posted on Autism

Autistic adults experience high rates of negative life events

Autistic adults are vulnerable to many types of negative life experience, including employment difficulties, financial hardship, domestic abuse and ‘mate-crime’, according to new research published today in the journal Autism Research.

This research highlights the challenges that autistic adults face in our society. With the right support many of these events are preventableSarah Griffiths

These negative life experiences could partially explain higher rates of anxiety and depression symptoms and lower life satisfaction in autistic adults compared to non-autistic adults.

Mental health conditions, such as anxiety and depression, are extremely common in autistic adults. Negative life experiences increase the risk of anxiety and depression in the general population, yet few studies have investigated whether vulnerability to these types of experiences might be responsible for higher rates of depression and anxiety and autistic adults.

One barrier to investigating vulnerability in autism is the lack of suitable measures. The research team, based at the University of Cambridge, Autism Research Centre, therefore developed a new measure called the Vulnerability Experiences Quotient (VEQ).

The team worked with an advisory group of autistic adults to develop the measure to ensure that it included experiences that autistic people felt were relevant to them. The VEQ asks participants whether they have experienced 60 negative life events, across a wide variety of settings, and including both adulthood and childhood experiences.

426 autistic adults and 268 non-autistic adults completed the VEQ via an online survey. The two groups had similar levels of educational attainment and the majority of autistic adults did not have intellectual disability. The autistic participants reported higher rates of 52 of the experiences in the VEQ.

This included items relating to financial hardship: 45% of autistic adults said they had had a period of life without enough money to meet basic needs, compared to 25% of the non-autistic adults; domestic abuse: 20% of autistic adults that had been in a relationship had been sexual abused by their partner, compared to 9% of the non-autistic adults, and ‘mate-crime’: 70% said they had been bullied by someone they considered to be a friend, compared to 31% of the non-autistic adults.

Participants also completed measures of anxiety and depression symptoms and a brief life-satisfaction scale. Autistic adults reported higher levels of depression and anxiety symptoms and lower levels of life satisfaction.

Those individuals with the highest number of negative life experiences on the VEQ also experienced the highest number of current anxiety and depression symptoms and the lowest current life satisfaction.

Although this study cannot prove that these negative experiences cause depression, anxiety or lower life satisfaction, as these are just associations, these findings are consistent with the idea that vulnerability to negative life experiences is partially responsible for higher rates of anxiety and depression and lower life satisfaction in autistic adults.

Lead author Dr Sarah Griffiths, said: “This research highlights the challenges that autistic adults face in our society. With the right support many of these events are preventable. We need to ensure that all autistic adults have appropriate support to reduce their vulnerability and to improve their mental health outcomes.”

Dr Carrie Allison, one of the Cambridge research team said: “The results of this study are a wake-up call indicating the serious extent of negative experiences that autistic adults suffer in most areas of their lives. This study focused on intellectually able autistic adults due to the online survey method. Future work will focus on adults with intellectual disability who may have a different set of vulnerabilities.”   

Professor Simon Baron-Cohen, director of the Autism Research Centre at Cambridge, said: “This research is vital to inform Government policy makers worldwide about the appalling violations of autistic people’s human rights. Our next step will be working hard to translate these findings into new policies, such as the need for every autistic person to have a life-long support worker to whom they can turn to help them navigate the world”.

Clara, an autistic adult from London commented on the study: “This research is so important to me. Despite being intelligent and good with people, I’ve had too many negative challenging situations in my life – with work, close relationships, access to health, social services, and education. It has affected, and continues to affect my mental health”

This study was funded by the charities Autism Research Trust and Autistica. The research also benefited from funding from the Queen Anne’s Gate Foundation, Mishcon de Reya LLP with support from Gesher School, the NIHR CLAHRC East of England and the IMI AIMS2TRIALS.

Posted on Pain Management

Killing pain without hurting the body: Novel compound that is potentially safer than current drugs

Pharmacodynamics and Pharmacokinetics of AD732: A Novel Pyrazole Derivative

Novel compound “AD732” shows analgesic and anti-inflammatory properties, but with fewer side effects than standard non-steroidal painkillers CREDIT Ritsumeikan University, Japan

Muscular pain, osteoarthritis, inflammatory bowel disease, and headaches have something in common—they are the result of various inflammatory processes that occur inside our body. The standard treatment, among other recourses, includes administration of non-steroidal anti-inflammatory drugs (NSAIDs). By inhibiting either of the enzymes (cyclooxygenase-1 or -2, also known as COX-1/COX-2) present in abundance at biological sites of inflammation, NSAIDs minimize pain and combat inflammation. But there’s a flip side—they can also cause serious side effects that result in heart failure, kidney malfunction, and stomach ulceration. It appears that to kill pain, we hurt our bodies.

This is why, for some time, efforts have been directed at finding safer non-steroidal anti-inflammatory and analgesic drugs. Most recently, a compound labeled AD732 has been synthesized, which shows promise in this direction. Now, in a new study published in the European Journal of Pharmaceutical Sciences (paper made available online on November 21, 2021, and published in Volume 168 of the journal on January 1, 2022), researchers led by Dr. Kikuko Amagase from Ritsumeikan University, Japan, and Prof. Adnan A. Bekhit, from the University of Alexandria, Egypt, have explored the therapeutic efficacy and side effects of this compound in rat models. “In a previous study, we synthesized this compound AD732. In this study, we compared it with two standard pharmaceutical drugs—indomethacin, a prototype NSAID, and celecoxib, a COX-2 inhibitor.” explains Dr. Amagase. “We aimed to assess its efficacy and adverse effects while relieving both acute and chronic pains.”

The researchers tested AD732’s anti-inflammatory properties in rat models of paw edema and granuloma. They tested its analgesic properties in a rat model of hyperalgesia and with hot plate tests, where a rat is placed on a temperature-controlled heated plate and its responses are monitored for signs of pain. The results were encouraging. AD732 showed higher anti-inflammatory and analgesic effects than the standard agents, while showing no ulcerogenic effects and causing minimal harm to kidney function.

Further, upon in vitro investigation of its mechanism of action, the scientists found that AD732 was a less potent inhibitor of COX-2 than celecoxib, which may indicate a lower potential for cardiovascular toxicity. Their inference is premised on prior studies, where highly potent COX-2 inhibitors have been noted to cause serious cardiac damage. For instance, rofecoxib (popularly known by the brand names “Vioxx,” “Ceoxx,” and “Ceeoxx”), a selective COX-2 inhibitor, drew flak from the New England Journal of Medicine for significantly increasing the risk of heart attacks and was subsequently withdrawn from the market in 2004.

But despite being a less selective inhibitor of COX-2, AD732 had proved very therapeutically effective, as previously mentioned, particularly in inhibiting rat paw edema. This seems, to an extent, to be counterintuitive. Dr. Bekhit muses, “Our findings on AD732’s lower COX-2 inhibition could indicate that this is not the sole mechanism contributing to its anti-inflammatory actions.” Further in-depth research is needed to determine its precise mechanism of action.

Nevertheless, as Dr. Amagase explains, “It may be concluded that compound AD732 appears to be a safer and more effective molecule with promising potential for the management of pain and inflammation, even in difficult diseases such as ulcerative colitis and Crohn’s disease.”  Perhaps, soon, we will be able to kill pain without hurting our bodies.