Pioneering new multiple sclerosis (MS) research projects – including three in the UK – have been awarded £1.2million as part of a renewed global effort to stop the condition.
The International Progressive MS Alliance will share the funds – up to £65,000 each – between researchers around the world through 19 Research Challenge Awards.
Each winning project shares a united goal of discovering what causes MS to progress.
By developing a clear understanding of what leads to MS progression, it is hoped this funding will speed up the development of much-needed new treatments for the condition.
Professor David Baker, from Queen Mary University of London, is one of three UK researchers who has been awarded funding.
His innovative project will explore how to protect nerve cells from becoming dangerously over-excited. Over-excited nerve cells can die, and nerve cell death plays a big part in MS progression.
Professor Baker explains: “We’ve developed a chemical that we believe can help calm over-excited cells and protect them from exhaustion.
“Based on a chemical our bodies make naturally, it can enhance a gate-like mechanism, which allows certain charged particles to exit the nerve cell. This prevents the build-up of excitability which can be dangerous, and lead to nerve cell death.
“If we can use our new chemical to control this function without affecting other cellular processes – therefore causing negative side-effects – and protect nerve cells from death in the process, it could be a complete game changer for MS treatment.”
Dr Don Mahad, based in Edinburgh, will also be awarded funding from the Alliance. Last year he and his team discovered that the diabetes drug pioglitazone could be another piece in the puzzle of stopping MS, through its ability to protect nerves from damage.
Their work, which so far has only been conducted in mice, can now be taken forward in experiments with human tissue.
“To stop MS from progressing, we need to be able to protect nerves from damage,” says Dr Mahad, senior clinical lecturer at the University of Edinburgh.
“Last year we found that our nerves have a natural protective response when myelin, the coating that protects them, gets damaged in MS. And in animal studies we were able to enhance that response with a drug that’s already available.
“We’re now able to take our findings forward to see if what we’ve found in mice is also true in brain tissue from people with MS. We also want to find out if nerve cells have other natural protective responses, and how we might help these processes along.”
At University College London (UCL), Professor Ken Smith will explore when the fatal injury that leads to nerve cell death in progressive MS happens.
His team will explore whether targeting oxygen shortage in the inflamed nervous system affects the subsequent accumulation of disability.
In addition to three UK projects, scientists in the USA, Italy, Australia, Finland, Germany, Netherlands, Canada, Belgium, Austria, Switzerland, Ireland and France will also be awarded funding.
Among some of the most exciting international projects are Professor Francesco Bifari’s work in Italy, which will test whether particular nutritional supplements in mouse models of progressive MS can increase cellular energy and mitochondria function in nerve and immune cells.
And in Germany, Professor Ludovico Cantuti-Castelvetri will be exploring whether a new antibody can help to clear damaged myelin out of the brain, and in turn slow brain damage.
Professor Alan Thompson, chair of the Alliance Scientific Steering Committee, says: “These awards represent an important advancement in progressive MS research and will build upon prior investments by the Alliance.
“We are greatly encouraged by the high quality and diversity of the funded projects. Successful results from these studies will greatly accelerate the development of new treatments for people with progressive MS.”
Dr Clare Walton, Head of Research at the MS Society – a funding Alliance member – adds: “We believe we can stop MS. And by finding out what drives MS progression, these projects will bring us one step closer to finding treatments for everyone.”
MS Trust expands two support programmes
The specialist MS nurse and advanced MS champion programmes are enabling more patients to access much-needed support
Two vital programmes to support people living with multiple sclerosis are broadening their reach in response to the increasing need from people with MS across the country, which has been exacerbated by the pandemic and the knock-on effect of a shortage of community resources and growing waiting lists.
The specialist MS nurse and advanced MS champion programmes, operated by the MS Trust, are both growing to help meet demand for people with MS who need greater support – something which has increased significantly during the pandemic, with support being scaled back or stopped for many amidst mounting pressure on NHS resources.
The MS nurse programme – which provides the NHS with a support package, including funding 80 per cent of the nurse’s role for the first 15 months in post – has recently moved into the Walton Centre in Liverpool to provide care across North Wales, with three more nurse roles planned across the UK this year.
The charity is currently undertaking its biannual survey of MS services nationally, assessing the landscape of support and the changes seen since 2018.
“We have three nurses planned for this year, with a basic plan of six over the next two years, and to scale up the programme in response to the need,” says Paru Naik, director of health professionals programmes at the MS Trust.
“In our survey, we will look at what’s happened, what services are no longer there, what the support is looking like. We’ll analyse the results and work out where there is the most unmet need and the least resource.
“Every person with MS should have access to an MS nurse as and when they need it, and you can identify the difference between having and not having access to that support.
“There are so many issues that people with MS face and the MS nurses help them navigate the situation, helping them to find the right resources and how to access them whilst working closely with neurologist and allied health professionals to ensure access to treatment and support.”
The advanced MS champion initiative, which delivers guidance to people with more advanced MS in navigating the health system and accessing resources, has also seen its value proven after a successful pilot in six sites across the UK.
The work to date with the advanced MS champions, who may be from either a nursing or therapy background, has enabled support to continue for this particularly vulnerable group of people, which is proving increasingly vital in meeting demand amidst ongoing backlogs.
“People with advanced MS can get easily lost in the system and end up going round in circles with little or no access to specialist MS care” says Paru.
“The waiting list increases are having a huge impact and there isn’t always the access to NHS resources. There are 130 people diagnosed with MS every week in the UK, and 40,000 with advancing MS who are not on any drugs, many of whom don’t have access to the acute sector.”
While both programmes had to be paused during the pandemic due to resource issues – both within frontline healthcare and the MS Trust, where its enquiry line became a hugely effective resource during times of lockdown – the charity is now stepping up to support specialist services at a time when it has never been more needed.
During the past 18 months, it was the MS Trust’s virtual support which proved invaluable for those who needed its support, with the increase in demand for its services necessitating rapid development of its enquiry line. The charity was able to access funding from the National Lottery Community Fund to support its scale-up, with 83p in every pound of its income coming from fundraising and no Government support being received.
“Frontline services were being re-deployed and it was very difficult for us to engage with health professionals at that time,” says Paru.
“We recognised people with MS needed a different kind of support, so deployed our own resources to help meet demand for our enquiry line.
“We always knew our two programmes were going to be re-started, they’re real USPs for us and we know only too well how vital they are for people with MS, but at that time it was a question of resource.
“We were suddenly inundated with enquiries, the vast majority of which were COVID-related, so we diverted our energy into how we could create a resource both we and health professionals could direct people to.
“Our website was also a priority, and we started to add online content based around COVID, includes videos, blogs and personal stories, to help support people remotely.
“This all happened as we were moving to work from home, with around 50 per cent of our team going on furlough leave, but the transition felt seamless. We recognised the need people with MS had for our support and we’re really proud of how we met that.”
Having relied on virtual means of communication during the pandemic, the MS Trust team are now returning to the office and are resuming face to face contact but will be following a blended approach of both going forward.
“Virtual will be right for some but not for others – for some, things will have been missed and lost, and it’s important we address that at the earliest opportunity,” says Paru.
“Multiple sclerosis is such a varied disease, no two people have the same set of symptoms. This is why specially trained nurses and therapists are so vital to people who live with MS.”
Brain molecule ‘wake ups’ cells that could help tackle MS
An immunological molecule called fractalkine can boost the production of brain cells that produce myelin, a key factor in diseases such as MS, a study shows.
Myelin is an insulating layer around nerves that is gradually worn away by inflammation in multiple sclerosis and similar diseases.
Without this layer, the nerve impulses that travel through the body are slowed, causing neurological problems.
Though there are therapies that manage symptoms or attempt to slow the progression of neurodegenerative diseases, effective treatments would require restoring lost myelin.
Finding methods to kick the myelination process into high gear is a crucial step in the quest for treatment.
The study was carried out by University of Alberta researchers.
Anastassia Voronova (pictured) of Department of Medical Genetics, explains that neural stem cells produce a variety of brain cells, including oligodendrocytes, a type of cell in the central nervous system and peripheral nervous system. Oligodendrocytes are the only brain cells that produce myelin.
“During development, these neural stem cells build the brain. In the adult brain, part of the reason they exist is to replenish damaged or lost cells, including oligodendrocytes,” she said.
“However, especially in humans, replacement of oligodendrocytes is very inefficient. The goal of my lab is to identify molecules that are capable of ‘waking up’ those neural stem cells we all have in our brain to replenish those oligodendrocytes.”
Voronova’s study showed that fractalkine — a molecule previously thought to have a role only in the immune system — noticeably stimulated the transformation of neural stem cells into oligodendrocytes.
“The [fractalkine] molecule and receptor work together to elicit a signalling cascade inside of the cell,” said Voronova.
“This is a really interesting era to be doing this science in. I think we’re just starting to appreciate the full spectrum of what these oligodendrocytes can do.”
Voronova’s team is now investigating the remyelination capacity of fractalkine in a mouse model of MS. Voronova also plans to examine whether fractalkine could affect myelination in other neurodegenerative disorders.
She added that the immunological nature of fractalkine could also be important for future drug development, as MS and neurodegenerative disorders have a strong immune component.
“Myelin is diminished in a variety of neurodegenerative disorders, which makes the idea of enhancing oligodendrocyte production, and therefore repair of the myelin, so exciting.”
MS and depression ‘increase risk of death and vascular problems’
Depression is common in people with multiple sclerosis (MS), and a new study shows that people with both conditions may be more likely to die over the next decade than people with just one or neither condition.
The study also found that people with MS and depression have an increased risk of developing vascular disease such as heart attack and stroke.
“These findings underscore the importance of identifying depression in people with MS as well as monitoring for other risk factors for heart disease and stroke,” said study author Dr Raffaele Palladino, of Imperial College London.
“Future studies need to be conducted to look at whether treating depression in people with MS could reduce the risk of vascular disease as well as death over time.”
The study involved 12,251 people with MS and 72,572 people who did not have MS. Researchers looked at medical records to see who developed vascular disease or died over a period of 10 years.
At the start of the study, 21 per cent of the people with MS had depression and nine per cent of the people without MS had depression.
The researchers found that people with both MS and depression had a mortality rate from any cause of 10.3 cases per 100,000 person-years.
Person-years take into account the number of people in a study as well as the amount of time spent in the study. The mortality rate for people with MS without depression was 10.6, for people who had depression without MS it was 3.6 and for people with neither condition it was 2.5.
Once researchers adjusted for other factors that could affect the risk of death such as smoking and diabetes, they found that people with both conditions were more than five times more likely to die during the next decade than people with neither condition.
People with MS without depression were nearly four times more likely to die than people with neither condition and people with depression without MS were nearly twice as likely to die.
For the risk of vascular disease, the rate for people with both MS and depression was 2.4 cases per 100,000 person-years; 1.2 for people with MS without depression; 1.3 for people with depression without MS; and 0.7 for people with neither condition.
After adjusting for other factors, researchers found that people with both conditions were more than three times as likely to develop vascular disease as people with neither condition.
“When we looked at the risk of death, we found that the joint effect of MS plus depression equaled more than the effect for each individual factor alone—in other words, the two conditions had a synergistic effect,” Dr Palladino said.
“A total of 14 per cent of the effect on mortality rate could be attributed to the interaction between these two conditions.”
A limitation of the study was that researchers did not have information on risk factors such as body mass index (BMI), which could affect the risk of vascular disease and death.
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