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MS research reveals sight breakthrough

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The findings come from a recent study held by UC Riverside School of Medicine

Vision in patients with multiple sclerosis (MS) could be improved through the use of medication, a new study has found.

A mice study investigated the effect of indazole chloride (IndCl) on the pathology and function of the afferent visual pathway for the first time, which includes the eyes, optic nerve, and all brain structures responsible for receiving, transmitting, and processing visual information.

“IndCl has been previously shown in mice to reduce motor disability, increase myelination, and neuroprotection in the spinal cord and corpus callosum,” says Seema Tiwari-Woodruff, a professor of biomedical sciences at the UC Riverside School of Medicine and the study’s lead author.

“Its effects in the visual system, however, were not evaluated until now.

“Our study shows the optic nerve and optic tract, which undergo significant inflammation, demyelination, and axonal damage, are able to restore some function with IndCl treatment with successful attenuation in inflammation and an increase in remyelination.”

In MS, damage can often be caused to the optic nerve and other parts of the visual system, which results in around 50 per cent of patients with MS experiences optic neuritis – inflammatory demyelination of the optic nerve – prior to showing initial symptoms.

Almost all MS patients have impaired vision at some point during disease progression. Symptoms can include eye pain, blurred vision, and progressive vision loss that can lead to blindness, among other visual impairments.

The researchers used IndCl to assess the impact on demyelinating visual pathway axons. The treatment induced remyelination and mitigated some damage to the axons that resulted in partial functional improvement in vision.

The visual pathway in mice is similar to that in humans, say researchers. In the lab, Professor Tiwari-Woodruff and her research group first induced the mouse model of MS. They let the disease progress for about 60 days, and when the disease reached a peak between 15 and 21 days, they administered IndCl to half the mice.

At the end of the experiment, they performed functional assay to measure the visual electrical signal, and immunohistochemistry to examine the visual pathway.

The mice that received the drug showed improvement in myelination, with visual function improving by about 50%.

“Measuring visual function and recovery in the presence of novel therapies can be used to screen more effective therapies that will protect axons, stimulate axon remyelination, and prevent ongoing axon damage,” says Professor Tiwari-Woodruff.

Currently approved MS drugs reduce inflammation but do not prevent neurodegeneration or initiate remyelination. Further, they only partially prevent the onset of permanent disability in patients with MS.

“We treated the MS mice with IndCl at peak disease,” Professor Tiwari-Woodruff says.

“If the brain is highly diseased, some of the axons that could potentially restore visual function are too damaged and will not recover. There’s a point of no return.

“Our paper stresses that to acquire vision improvement, treatment must start early. Early treatment can recover 75%-80% of the original function.”

Tiwari-Woodruff stresses that although additional studies are required, the new findings show the dynamics of visual pathway dysfunction and disability in MS mice, along with the importance of early treatment to mitigate axon damage.

“There is a strong and urgent need to find a therapeutic candidate that restores neurological function in patients with MS,” Professor Tiwari-Woodruff adds.

“Therapeutics must target remyelination and prevent further axonal degeneration and neuronal loss. The good oestrogens, which have neuroprotective and immunomodulatory benefits, could be candidates for MS treatment.”

MS

“I found out I was pregnant shortly after my MS diagnosis”

It has been a whirlwind last few years for MS patient Annie, whose diagnosis, sparked from getting a fly stuck in her eye, came just weeks before her first pregnancy.

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MS diagnosis
Annie and her daughter Aubrey

A Multiple Sclerosis (MS) diagnosis is often a life changing event, with huge worries and concerns being overriding emotions for those who are told they have the condition.

This was exactly the case for 30-year-old Annie, who found out she had MS just weeks before she discovered she was pregnant with her first child.

For years she had been suffering with fatigue and tiredness, but despite spending hours doing her own research she could not work out what was causing it.

After numerous hospital visits, she was given a diagnosis of chronic fatigue syndrome, although Annie said she ‘never really felt like that was the correct diagnosis’ for her.

It would take a strange coincidence for her to eventually discover the problem, after she got a fly stuck in her eye in June 2020.

 

She experiences blurred vision for a few days following this, which led her to visit the options who referred her to John Radcliffe Hospital (JR) in Oxford.

An MRI scan was taken with doctors finally unveiling the MS, giving her the diagnosis a day later.

This would be a lot to take for most people, but Annie had an extra layer added to this shortly afterwards when she found out she was pregnant.

This led her to be concerned about what affect her diagnosis would have on her child.

“I did quite a bit of research myself and I spoke to my midwife,” she said. “I was also under care at the JR called Silver Star, which is for people with a high-risk pregnancy.

“I asked a lot of questions just really regarding my baby and if it would affect her in any way and I was reassured that there’s really a minimal chance that it can be passed on.

“That was my main concern but I also looked at if I would get more symptoms, but it seemed from the research and speaking to people that actually MS symptoms seem to stop when you’re pregnant because of your hormones.

“So I actually really enjoyed it, I had quite a nice pregnancy.”

Thankfully there were no issues during her pregnancy and she gave birth to a healthy baby girl named Aubrey in April.

However for this reason she did not want to start any form of treatment until after this and was worried that symptoms would start soon after.

Annie admitted her diagnosis was a shock as she did not know much about MS nor did she know anyone who had it.

However she was determined to not let it change anything.

“When I found out initially, that day was quite shocking,” Annie said. “But I’m quite a practical person so I just got on with it, that was where I was at.

“Since I’d had this for years and it’s not changed who I am or affected me massively, it’s just a thing I have.

“I didn’t want it to define who I was or be an excuse for not doing things. In the future it might be more of an issue and hold me back a little bit more, but at the moment it’s just one of those things that I can’t change.

“I’ve got so I might as well just live with it. I’ve told my close friends and family about my diagnosis, but I don’t feel like the world needs to know.”

Annie’s positive outlook is what has allowed her to continue her life to live her life and she has certainly not let it stop her doing anything.

She was midway through her Masters degree when she was given her diagnosis, but she managed to finish that and continues to work full-time as a human resources advisor.

This was challenging for her when it came to things like long periods of concentration or trying to view data, but as mentioned previously Annie never wanted MS to be an excuse for anything.

Currently she says she has not had many issues with the condition, saying the tiredness felt by many is something she is used to now.

However she has been receiving help from the MS Trust, which was her first destination when she wanted to learn more about it.

“I went to the MS Trust and the MS Society’s websites because that was the most reliable information.

“When I was first diagnosed I didn’t know anyone with MS so it was a good place to start some research and actually understand what it was and how it could affect me.

“After a diagnosis you might go online and look at a website that’s not hugely reliable and it’s always the worst case scenario that you read about.

“But things like its forums and having people that are actually going through the same stuff, it was good to look at.”

Looking to the future Annie says she would love to eventually give back to the MS Trust, suggesting she could attempt to climb Mount Kilimanjaro in a fundraising effort.

At the moment however she is just looking to live life normally.

Having just turned two months, Aubrey is healthy and has had no issues impacting her from her mother’s MS.

Annie confessed looking after her daughter keeps her busy but she wouldn’t have had it any other way.

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MS

Pioneering MS research supported with £1.2m in grants

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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.”

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MS

‘Effective MS treatments should be available for everyone with MS, wherever they live in the UK’

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A medication for people with relapsing MS has been denied recommendation for NHS use England and Wales, despite it gaining approval from Scottish regulators earlier this year. 

Ozanimod, or Zeposia, is a disease modifying therapy which is taken as a tablet and traps immune T-cells in the body’s lymph nodes.

In a two-year clinical trial, it was shown to reduce relapses in those with active relapsing remitting MS by around 38 per cent, compared to beta interferon, an existing MS treatment.

However, the National Institute for Health and Care Excellence (NICE) has decided not to recommend it for people with relapsing MS on the NHS in England and Wales, confirming its provisional decision from January – despite the fact it was given approval by the Scottish Medicines Consortium (SMC).

Following a final review of evidence, including that from charities, NICE found that ozanimod was not cost effective enough to be recommended for use on the NHS. NICE considered that ozanimod’s effect on disability progression was uncertain.

MS charities have spoken of their disappointment at the decision, particularly given its approval for use in Scotland. 

“It’s disappointing that NICE has made this final decision not to recommend ozanimod as a treatment for relapsing multiple sclerosis in England,” says Fredi Cavander-Attwood, policy manager at the MS Society. 

“Oral treatments, like ozanimod, are limited and not allowing people this option could deny them a convenient way to manage MS symptoms.

“This rejection also highlights the inequities in access to treatments around the UK, as people living with MS in Scotland were granted access to ozanimod in February. 

“Effective MS treatments should be made available for everyone living with MS, regardless of where they live in the UK.”

In March 2020, ozanimod was licensed by the European Medicines Agency (EMA) to treat people with relapsing MS who have active disease.

Scotland is now the only nation in the UK to approve ozanimod, with 15 disease modifying therapies now available on the NHS in the country. The NICE decision applies to England and Wales, with decisions from the body reviewed by the government in Northern Ireland but are generally adopted. 

 

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