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Research

Brain cancer research backed by award

Dr Sharel Peisan E’s research into nanoscale electrochemistry of brain cancer cells has received the Springboard Award

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Pioneering brain cancer research has been backed by a new six-figure award, to support its ambition to advance diagnosis and treatments. 

Dr Sharel Peisan E, a chemistry lecturer at Teesside University, will examine the nanoscale electrochemistry of brain cancer cells.

Using a multifunctional nanoscale electrochemical imaging platform, Dr E will be able to take a closer look at brain tumour cells and their processes to gain a better understanding of their biology.

The technology uses tiny electrodes to gain an extremely close and detailed visualisation of the biology of living cells.

This research project, backed by an award of £100,000, aims to explore how brain cancer reacts to different therapies on a cellular level, which will be applied to improving or designing more effective treatments for cancer patients.

It will also be able to provide insight into other neurodegenerative diseases such as Alzheimer’s in much the same way.

Glioblastoma is one of the most devastating cancers, although its biology remains somewhat of a mystery in cancer research, with brain cancer cells being difficult to analyse using current methods of examination,” explained Dr E, who is based at Teesside University’s National Horizons Centre.

NHC National Horizons Centre

“My research will use advanced nanoscale imaging to provide a new view of the solid, liquid and gaseous processes, known as heterogeneous processes, on the cancer cells at the nanoscale, providing additional information on the glioblastoma biology which has previously been unattainable through microscopic techniques, allowing us to improve current diagnostics and treatments.”

Dr E won the grant from the Academy of Medical Sciences as part of the Springboard Award, which provides funding and career support for innovative bioscientists.

Teesside University’s National Horizons Centre, based at the Darlington campus, is a £22.3million centre of excellence for innovation and training in biosciences and healthcare, with strength in cancer research.

Professor Vikki Rand, interim director of the National Horizons Centre, said: “Here at the National Horizons Centre, we are positioned at the forefront of the biosciences and healthcare sector, leading groundbreaking research to drive progress in key areas including disease and climate change.

“We are devoted to gaining as much knowledge about cancer as we can, and our work in cancer research is particularly impressive, directly influencing the wider healthcare sector through studies which inform new and improved therapies to help real patients which is, after all, what our research is all about.

“Grants such as the Springboard Award from the Academy of Medical Sciences are extremely important and we are thrilled that Dr E has won this very substantial funding for her research.”

Research

New means to define Huntington’s could revolutionise drug trials

A novel staging framework that assesses the progression of HD has been developed

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A novel staging framework that assesses the progression of Huntington’s disease (HD) has been developed, paving the way for clinical trials of drugs in the earliest phase of the disease. 

The Huntington’s Disease Integrated Staging System (HD-ISS) groups together people with HD according to their underlying biological (including genetic), clinical, and functional characteristics. 

It is the first time ever a staging system – similar to how cancer is staged 0 to 4 – has been developed for a genetic neurological condition.

HD is a progressive genetic neurodegenerative disorder, that affects about 1 in 10,000 people in the UK.

There are currently no approved therapies that can slow the disease progression. 

The new evidenced-based framework also includes criteria to biologically define HD stages across the whole trajectory of the disease from birth, which has never previously been done before.

The HD-ISS staging criteria covers the entire disease spectrum, beginning at Stage 0 (individuals with the HD genetic mutation without any detectable pathological change), Stage 1 (subsequent progression marked by measurable indicators of underlying pathophysiology via biomarkers), Stage 2 (a detectable clinical phenotype), and finally Stage 3 (decline in function).

At this stage, the HD-ISS is for research purposes only, not clinical practice.

“HD families have long known that signs and symptoms begin decades before the classical motor onset diagnosis that occurs late in the disease course,” said first author Professor Sarah Tabrizi, of UCL Huntington’s Disease Centre, UCL Queen Square Institute of Neurology, and UK Dementia Research Institute at UCL.

“We developed the HD-ISS using state-of-the-art evidence-based methodology and it will revolutionise our ability to evaluate novel disease-modifying therapeutics much earlier in the disease course, when therapies will likely have the best chance of slowing disease progression and providing clinical benefit.

“This research required the selflessness and dedication of thousands of research participants from HD families, to whom we are immensely grateful.

“Ultimately, our goal is to deliver therapeutics at the right time to effectively treat this disease. Ideally, we’d like to delay or prevent neurodegeneration while function is still intact, giving people with HD many more years without impairment. 

“The HD-ISS is an important tool that will allow us to do this as therapeutics emerge.’’

The HD-ISS defines groups of people with HD with similar prognostic characteristics for research purposes and will facilitate data comparison across different trials and studies, expediting drug development, and aid in communication between different stakeholders, from HD families to health policy professionals.

Importantly, this new biological research definition of HD will allow evaluation of novel therapeutics in people in the very early stages of disease, before they show overt clinical signs; this will likely provide the best chance of substantially slowing disease progression and offer PwHD the greatest clinical benefit.

The HD-ISS was developed as part of the HD-RSC in partnership with UCL, CHDI Foundation and C-Path and involved academic researchers, clinician scientists, and representatives from pharmaceutical and biotech companies that have clinical HD programs.

Dr Cristina Sampaio, chief clinical officer at CHDI Management/CHDI Foundation, said: “As a validated staging system, the HD-ISS has the potential to transform how HD clinical research is conducted, enabling study of the earliest disease phases and planning of preventive clinical trials, as well as facilitating data aggregation and sharing.

“For HD families it should be emphasised that this is for research purposes only, it will not affect their clinical care.”

Current clinical diagnosis of HD relies on observation of established clinical signs (primarily involuntary motor signs, but also cognitive impairment and behavioral changes) that emerge late in disease course. 

This diagnostic approach was developed before the discovery of the huntingtin gene and the consequent genetic test for the CAG expansion – the mutation in DNA that causes the disease – and before the current understanding of disease-related pathobiological changes that develop many decades before these observable clinical signs.

The disease phase prior to this current diagnostic stage has been variously described as ‘presymptomatic’, ‘premanifest’, or ‘prodromal’, poorly defined terms that make it difficult to compare data and findings across trials and studies.

Dr Emily Turner, executive director of the Huntington’s Disease Regulatory Science Consortium (HD-RSC) at the Critical Path Institute (C-Path), said: “The HD-ISS truly represents a pivotal, collaborative moment in Huntington’s disease clinical research, and the Critical Path Institute is proud to have helped facilitate the development of this much needed staging system.”

President & CEO of the Huntington’s Disease Society of America (HDSA), Louise Vetter, said: “This is a positive and powerful development that brings the lived experience of people with HD to the heart of research and provides a path forward for people earlier in their HD journey to be a part of clinical research. 

“The overwhelming response from HD families has been ‘What took so long?’”

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Tech

ONWARD – making the impossible possible

CEO Dave Marver discusses its pioneering work in spinal cord injury and the new hope for people living with paralysis

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Professor Gregoire Courtine, Dr Jocelyne Bloch, Dave Marver

The concept of three people living with complete paralysis regaining the ability to walk independently is something that, in the very recent past, would have been dismissed as being impossible – but through the work of ONWARD, this one-time ‘impossibility’ is now becoming reality. 

For years, spinal cord injury has been regarded by many as the ‘graveyard of neuroscience’, where hope was in short supply and the outlook for those daring to dream of the day that may change was bleak. 

But now, through the efforts of pioneers who have led the research breakthroughs that are now shaping reality, the ability of technology to change lives is being seen by the whole world, with people watching in amazement as paralysed patients rediscover the ability to move. 

After being implanted with spinal stimulation technology developed by ONWARD – the first time its epidural electrical stimulation (EES) had been trialled in humans – all three participants who were part of the STIMO-BRIDGE trial were able to take steps independently within a single day.

After five months of rehabilitation, they were also able to use their legs to stand, walk, swim, and/or cycle. They also regained control of their trunk muscles. 

Such colossal steps forward in SCI are now giving new hope to people living with paralysis – and are helping to show, rather than being impossible, what could become the new possible for the future. 

“We were very pleased with the results of STIMO-BRIDGE, although we as a company are not going to be pleased with just impacting subjects in a clinical trial,” Dave Marver, CEO of ONWARD, tells NR Times. 

“Our job and our unique role is to scale these therapies so they can provide benefit to hundreds of thousands of people with spinal cord injury around the world. 

“These results show great promise, but we still have a tremendous amount of work to do to achieve our vision.” 

And for ONWARD, that vision is to change the lives of people living with SCI globally, to enable them to enjoy and live their lives in the ways that matter most to them. 

Established in 2014 to focus specifically on SCI, the venture has led truly groundbreaking research into this long-underserved area. 

Founded by neurosurgeon Dr Jocelyne Bloch and Professor Gregoire Courtine, Swiss-based ONWARD has taken decades of research and translational science to bring to fruition two viable commercial solutions. 

With its ARC EX and ARC IM devices, ONWARD – backed by many of the leading European life sciences venture capital investors – has led the charge on redefining the outlook for SCI patients. 

Its ARC IM, recently subject to the STIMO-BRIDGE trial, consists of an implantable pulse generator and lead that is placed near the spinal cord, controlled by wearable components and a smartwatch. A pivotal trial is set to begin within the next 12 to 18 months. 

The ARC EX is an external, non-invasive wearable stimulator and wireless programmer, which targets the rediscovery of upper body movement. Currently subject to the international Up-LIFT trial – the largest SCI trial of its kind – it completed enrolment of 65 participants ahead of schedule, despite the many challenges presented by the COVID-19 pandemic.

Currently being trialled at sites across the world – including in the NHS Greater Glasgow and Clyde (NHSGGC), as well as Neurokinex sites in England – the aim, pending necessary approvals, is for a commercial launch in the first half of 2023. 

But while the excitement at the potential of ONWARD is palpable, with the first introduction of its technology into rehabilitation centres across the United States, UK, France, Germany and the Netherlands potentially barely a year away, Dave is keen to ensure expectations remain realistic.  

“Certainly this will give hope to people, and I think the fact we enrolled all 65 subjects in Up-LIFT ahead of schedule, despite all the challenges of clinics closing and difficulties with quarantines and so forth, speaks to the enthusiasm that the clinical community has for this therapy,” he says.

“They have really embraced it, as the participants did in STIMO-BRIDGE. We, and they, are showing what is possible. 

“But I do think it’s important to not overstate it, I don’t want to create false hope, because these subjects really committed themselves to the therapy and to the rehabilitation process. 

“I think there is great potential that many people with paralysis will be able to stand again with the benefit of our therapies, maybe take some steps. But then it really depends on their particular circumstances and their overall level of health, their willingness to commit to rehabilitation, whether they can go further than that. 

“And, of course, not everyone with spinal cord injury, desires necessarily to walk again, they may have other priorities. And that’s why ONWARD is also committed to addressing other challenges that affect the quality of daily life, such as blood pressure and trunk control and use of better use of the upper extremities. 

“And then in the future, we’ll be looking at incontinence and restoration of sexual function, the whole battery of things that people with SCI have to contend with.”

Through its longstanding and deep-rooted commitment to the SCI community, ONWARD has secured relationships with of some of the world’s leading organisations in this area, including the International Spinal Research Trust and the Christopher & Dana Reeve Foundation. The latter has even become ONWARD shareholders, to help further its pioneering work. 

For Dave, while the word ‘pioneering’ is well-used, for ONWARD, it is also well-earned. 

“I think we are seen as pioneers in this area because we’ve chosen to focus on serving the spinal cord injury community,” he says. 

“It’s a smaller population than other populations with movement-related challenges, like stroke and Parkinson’s, for example. Most businesses orientate toward the largest potential markets, whereas our founders really had a passion for helping people with spinal cord injury. 

“And that remains the core vision, that was their raison d’être, and it’s with that commitment and determination that we have achieved such progress. 

“We haven’t partnered with existing spinal cord stimulation companies, we’ve developed our own technology platform that is built for the specific purpose of not stimulating the spinal cord for pain management, but stimulating the spinal cord to restore strength and function.

“But I think the progress we have made also reflects the close collaboration that we enjoy and value with our scientific partners. We have a group of people so committed and driven by our mission, which I think is why we make the progress we have done. 

“We develop that lead together in a very rigorous way, with our vision at the heart of that.”

Constantly looking to the next innovation and how its technologies can be even more beneficial to those who need them, ONWARD is also considering how, post-commercial launch, its ARC EX could be used remotely. 

“Later, we’ll be seeking approval for it to be used in people’s homes, so they can conduct periodic sessions maybe once or twice a week in their homes to continue gains that they have observed in the clinic, and build on those gains,” says Dave. 

“We’ll be looking at a successor study to Up-LIFT which would look at safety and performance when used in the home. 

“Without question, it’s important with spinal cord injury to be able to operate this technology, which is why we were keen to incorporate voice activation into the system. Both of our platforms can be programmed by the clinician, but in the future may be operated by and used by the injured with their voices. 

“But very importantly, we do our best to connect as frequently as possible with people with injury to inform the design of our product platforms, and inform our future direction as a company. 

“We consider ourselves part of the community, so that feedback to ensure the design of our technologies is really usable and accessible, in my view, is vitally important.”

And with such huge advances and new-found hope for the future, many conversations have turned to whether SCI may be curable. 

“I wouldn’t rule anything out, with human ingenuity and so forth, but what I would say is more realistic at this point is to have optimism – quite a bit of optimism – that movement and strength and function can improve, and in some cases, be restored with the benefit of therapies like ours,” says Dave. 

“Perhaps other therapies and technologies will emerge, if you look at how far we have come. But for us, our vision is to support the SCI community around the world through our therapies, and we’ll continue to do that. 

“We’re making steady progress across all areas of our plan, and while what we’re doing is difficult and complex, I’m confident we will come through.”

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Neuropsychology

Trauma of LGBTQ+ sexual abuse in military revealed

Groundbreaking new report says tailored support and dedicated research must be made a priority

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Support and research must be made a priority in tackling the “hidden and under-reported” issue of sexual abuse of LGBTQ+ service personnel in the Armed Forces, a groundbreaking new report has concluded. 

The Exit Wounds report has identified the scale of LGBTQ+ survivors in the Armed Forces and the trauma that they faced during their time in service, and continue to face in living their lives outside of the military as a result of Military Sexual Assault (MSA).

Through research with survivors, veterans’ support charity Forward Assist has shone new light on the psychological trauma from experiences at the hands of colleagues in the military – an institution where, prior to 2000, serving members of the LGBT community could be expelled on the basis of their sexuality. 

And through gathering the experiences of veterans from the LGBTQ+ community, Forward Assist – and its women veteran-specific sister organisation Salute Her UK – have recommended a raft of changes to help improve the reality for current and future members of the Armed Forces. 

They include: 

  • the UK Office for Veterans Affairs must bring together veterans who are ‘experts through experience’ with organisational leaders and researchers to address key issues facing the LGBTQ+ community
  • The Government must initiate an independent and robust reporting system for survivors who wish to report historic abuse
  • Veterans must be supported by properly qualified trauma informed therapists and experienced support workers to deliver the help they need
  • The UK should follow the lead of the US Department for Veterans Affairs and publish LGBTQ+-specific veteran healthcare information
  • Large-scale academic research must be commissioned to examine the true long-term impact of MSA and MST on LGBTQ+ veterans 
  • More specialist resources be made available in the NHS to support LGBTQ+ veterans who have experienced sexual assault and trauma.

Pioneering Forward Assist – which works nationally from its North Tyneside base – has a strong record in supporting veterans directly while also campaigning for institutional change, and is leading from the front on this issue by introducing a role within its Family First support team for an LGBTQ+ veteran care co-ordinator.

“Sadly, research into the lived experience of LGBTQ+ individuals affected by Military Sexual Assault and associated trauma is currently non existent in the UK,” said former Royal Marine and qualified social worker Tony Wright and mental health therapist Paula Edwards, who lead Forward Assist and Salute Her UK. 

“We know MST is associated with poor mental health, interpersonal and physical relationship difficulties and appears to be more influential in the development of PTSD. 

“What is particularly traumatic for LGBTQ+ veterans is that not only were they abused (often targeted because of their sexuality) but blackmailed not to report it, and if they did, were dishonourably discharged.”

The research gathered the experiences of 20 LGBTQ+ survivors of Military Sexual Assault (MSA), aged between 43 and 67, who had been part of the Army, Navy and RAF.

The distressing experiences of many centred around rape or assault to ‘make them straight’, with many living in fear of the consequences of them being ‘exposed’ for being who they are. 

“If there was even a whiff of someone being gay, SIB would plant officers in the unit. That person would try it on with you and if you responded, you would be arrested and kicked out,” said one.

“I had to hide who I was for such a long time. I still conceal who I am. The consequence of my sexuality is that I don’t know how I am anymore,” said a veteran. 

“I got a fellow soldier to break my wrist so I could go to hospital and away from it all. I couldn’t cope,” added another.  

Many spoke of resultant psychological health issues including OCD, self-harming and bulimia, with many turning to alcohol and substance abuse. 

“I have PTSD, anxiety and depression. I rarely leave the house. I struggle to look after myself and have no energy for anything,” said one veteran. 

Another heartbreaking testimony read: “I live in supported accommodation. I feel suicidal every day and want to die. I have tried to hang myself quite a few times. I lost everything, how do you come back from that? The constant embarrassment and shame of letting my family down, and myself.”

Tony and Paula, who support thousands of veterans both in-person and online, said MST is a hugely prevalent issue within the veteran community in general, but specific intervention is needed for the LGBTQ+ ‘hidden population’.

“The unique aspects of sexual assault in a military context and the bizarre expectation that the victim must continue to work and/or live in close proximity to the perpetrator has a unique influence on how trauma and the inevitable fundamental feelings of betrayal manifest themselves during and after military service,” they said. 

“Team Forward Assist and Salute Her UK are committed to offering person-centred, needs-led, clinical support services to traumatised veterans with LGBTQ+ and related identities.”

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