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Groundbreaking research into MS could enable development of new treatments

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The research comes from the MS Society Edinburgh Centre for MS Research

The types of nerve cells which are lost through developing Multiple Sclerosis (MS) have been identified for the first time, in a breakthrough which could yield the development of new nerve-protecting treatments.

In a new study, researchers found that the inhibitory interneurons are lost in people who have MS.

Previously, it was only known that myelin, the protective coating around nerves, is damaged in MS – but pinpointing the selective loss of specific nerve cells has now been established.

The research, from the MS Society Edinburgh Centre for MS Research, could now lead to steps forward in the development of treatments to help protect the nerves most at risk.

Using brain tissue samples from the MS Society Tissue Bank, Professor Anna Williams and her team found a dramatic reduction in the number of inhibitory interneurons in tissue from people who had been living with MS, compared to people without the condition.

Another type of neuron – stimulating neurons – remained the same, even in people who had MS for decades.

Current treatments for MS target the immune system and reduce damage to the myelin, but by identifying how to replace lost myelin and protect nerves is the goal for researchers – and has been brought closer by this research.

“Our research has shown that a specific type of neuron, called an inhibitory interneuron, is damaged in people with MS,” says Professor Williams, who led the study.

“This is really important because, in the search for new treatments, it focuses our efforts on trying to stop the damage and death of these special cells.

“Our next step is to convert this knowledge into new treatments that protect nerves and prevent neurodegeneration – and ultimately disability – in people living with MS.”

The research team also generated a new mouse model of myelin damage, which showed the same selective loss of inhibitory neurons seen in humans – showing that myelin damage leads directly to nerve damage.

Researchers will now be able to test new treatments in the mice to see if they can prevent the inhibitory neurons from being damaged. This will help develop new treatments to protect nerves in MS.

Dr Lida Zoupi, who worked on this study, says: “In our mouse model, we show that demyelination directly leads to neurodegeneration, answering a long-standing debate between MS researchers in the process.

“By confirming this, we have a vital new insight into the mechanisms behind neurodegeneration, which could potentially be used as a model for the development of neuroprotective treatments.”

The research was hailed as a vital step in the ongoing efforts to understand MS and develop treatments as a result.

“We’ve made huge progress in finding treatments that target the immune system, but many people living with MS still don’t have access to effective treatments,” says Dr Emma Gray, assistant director of research at the MS Society.

“We believe this study represents a vital step in our mission to stop MS.

“Work like this, which is based at our Edinburgh Centre and used samples from the MS Society Tissue Bank, shows just how important charity funded research is to the overall research landscape, and we’re proud to have made it possible.”

MS

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.”

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MS

New research assesses impact of medication on MS symptom

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The Kessler Foundation are leading the research

The effect of medication Tysabri on cognitive fatigue in people with multiple sclerosis (MS) is to be analysed in a new research study.

The study will look at how the medication, also known as natalizumab, impacts cognitive fatigue in individuals with relapsing and remitting MS.

Most people living with MS report symptoms of cognitive fatigue, which can adversely affect their ability to perform activities in their everyday lives.

Statistics show that over 40 per cent consider such fatigue their most troubling symptom.

However, despite its impact, there are few treatment options, with none of the widely-used interventions used to slow progression of physical symptoms proven to treat cognitive fatigue.

In this study, led by the Kessler Foundation, the potential efficacy of Tysabri in alleviating cognitive fatigue among those with MS will be explored, in what could have transformational effects for people with the condition.

“Using this rigorous study design, we will add to our understanding of the neural mechanisms associated with Tysabri therapy,” says Dr John DeLuca, who is leading the study.

“We expect to draw firm conclusions about the effect of Tysabri on cognitive fatigue, which may be an important step toward expanding the options for treating this disabling symptom.”

The latest neuroimaging techniques are being used in the project, resulting in the identification and validation of a physiological biomarker, which will be used in determining the outcomes of this study.

The biomarker defines the brain activity patterns associated with cognitive fatigue, according to Dr DeLuca, senior vice president of Research and Training at Kessler Foundation.

“The biomarker enables us to objectively study disease-modifying therapies for MS such as Tysabri for their effects on cognitive fatigue,” he says.

The study will compare ten healthy controls with 15 individuals with MS who are planning to start Tysabri treatment.

During the initial six months of treatment, researchers will use functional MRI to measure the brain activation associated with cognitive fatigue induced by performing a cognitively challenging task.

They will also look at changes in the timing of the onset of cognitive fatigue as treatment progresses through the study, which is titled ‘Biomarker for Cognitive Fatigue using Functional Imaging in Multiple Sclerosis’.

It marks the latest major study from Kessler Foundation, a global leader in rehabilitation research that seeks to improve cognition, mobility and long-term outcomes, including employment, for people with neurological disabilities caused by diseases and injuries of the brain and spinal cord.

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MS Trust increases provision to support patients and the NHS

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The MS Trust is the only charity which provides additional specialist MS nurses into the NHS

Dedicated support for people living with Multiple Sclerosis (MS) is set to be increased through the addition of more specialist nurses and champions into the NHS and major investment in the development of an advice line.

The MS Trust is the only charity which provides additional specialist MS nurses into the NHS, and while it was forced to pause the initiative at the outbreak of the COVID-19 pandemic, it is now set to resume its NHS Specialist Nurse Programme with plans to create five additional roles.

The nurses are recruited and trained by the charity, in conjunction with local NHS partners, and are directed into areas with the greatest pressure on MS resources. The seven existing roles are majority funded by the MS Trust for the first 15 months, with the NHS then funding the positions once the positive impact of their roles is proven.

The charity is also set to further develop its pioneering MS Champions project, which has seen six people working within the NHS to provide signposting and guidance to some of the 40,000 people nationally who have advanced MS.

Early findings from the pilot scheme suggest each Champion delivers a saving of £150,000 per year to the NHS through relieving pressure on GP and A&E visits, and the MS Trust is targeting the addition of a further three roles.

Significant investment has also been made in the Trust’s enquiry line, which saw a surge in enquiries during the pandemic amidst resources being cut back elsewhere. Supported by National Lottery funding, the charity has been able to significantly upgrade its telephone system to develop the capacity of its service.

“Last year was a bit like walking through treacle. Now we’re out of the treacle and are building and future proofing what we do,” says David Martin, CEO of The MS Trust.

The charity, which helps more than 10,000 people with MS every year, is a key partner of the NHS through its funding of specialist MS nurses and champions.

“Our nurse programme has become well established, we have provided seven so far and we are seeing the difference they can make. MS nurses may ordinarily work with around 300 people, whether that is through face-to-face, telephone support or drug monitoring, but in some areas that will be over 1,000,” says David.

“Through our intervention to help recruit, train, fund and mentor a new nurse, that can help ease pressure significantly. It is my personal hope that we will add five more nurses, which would make a huge difference to the lives of so many people living with MS.”

The Trust’s MS Champions project is the only scheme of its kind and is also set to be extended after early indications of its success.

“Through appropriate support, signposting and guidance, we are saving the NHS hundreds of thousands of pounds, but are also crucially making a huge difference to people’s lives. This is why I work for The MS Trust, so we can create projects which make an impact like this,” says David.

And alongside supplying resources directly to the NHS, The MS Trust’s enquiry line is another significant asset, which has seen recent investment in its development. Demand for the service grew hugely during the pandemic, meaning the charity had to adapt quickly.

“We’re not a massive charity, we have a team of 30, but back in February we decided people were really going to need us via our enquiry line, so we put our resources into that,” recalls David.

“We have received more calls over the past year than ever before, April was our busiest month ever. Our phone system was very 20th Century, so it wasn’t a case of flicking a switch and resorting to home working, our team worked extremely hard to adapt.

“But through being able to secure National Lottery funding, we now have a whole new service. Our users won’t notice a difference, but for us internally, it’s geared up capacity and helped our team greatly. We are set up now for whatever the future holds.”

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