Tag: Auto immune disease

Constraints of my MS

Constraints of my MS

At the moment I feel I am doing very well with the acceptance of my MS.

Unfortunately this is such an unpredictable disease which I think makes it impossible to say that I have accepted every part of it.

Not many people know a lot about MS, I know I didn’t before I was told I have it.

I’ll explain a little about my MS. I say ‘my’ MS because not one person who has it is the same as another. We are all completely unique with our MS although the symptoms that we all have can be similar.

Now I am going to talk about one certain topic here but for you to understand I will have to go into detail about other symptoms which I will explain briefly with the aid of:

PAIN

Pain is only one of my symptoms!

This is probably one of the biggest things I have had to and still am learning to cope with!

Why do I have pain?

Pain

More than half of all people with multiple sclerosis will experience pain symptoms at some stage.

Pain can be defined as unpleasant sensory experiences. In MS this may encompass both ‘painful’ feelings and also altered sensations such as pins and needles, numbness, or crawling, burning feelings (known as dysaesthesia).

No two people will experience pain in the same way; it is very subjective and is best described by the person experiencing it.

Types of pain

There are two broadly recognised types of pain in MS:

Neuropathic pain

Also known as nerve pain, this is thought that this arises as a direct result of the damaged to the covering of nerves interfering with the normal transmission of information to the brain. However, the origin of most nerve pain is not fully understood. Examples of neuropathic pain include trigeminal neuralgia, an intense painful sensations in the face, and Lhermittes sign, sensations like electric shocks in the neck and spine.

Musculoskeletal pain

Also known as nociceptive pain. Nociceptors are pain receptors found throughout the body that respond to injury and inflammation. They send messages to the brain that are perceived as pain, usually in the joints or muscles. This type of pain is not directly related to MS, but may be worsened by it; for example, musculoskeletal pain can arise as the result of spasms or abnormal pressure on the muscles and joints due to changes in posture, typically in the back or hips.

Yes I take medication for it!

I’ve tried many different types of tablets, I’ve even tried holistic medicine like acupuncture which I find brilliant for relaxation but unfortunately the effect has never lasted long enough for me to use it as a regular way to self-control the pain.

So instead I have opted to continue with my cocktail of medication such as Pregabalin, Nortriptyline & Duloxetine

If you have clicked on the link for Duloxetine you will notice it is taken for depression, that’s a whole different topic which I’m sure I’ll speak about at some point!

So with my lovely cocktail of super strong neuropathic pain meds can you guess what my next biggest problem is with my MS?…..

Innovative research tool pinpoints potential therapies for multiple sclerosis

Shared on Facebook yesterday by an inspirational Mega Special lady & 5 x Paralympic medalist! Stephanie Millward.

I haven’t read this yet but I bet it is great news! Anything that will repair the nervous system must be amazing for us!!!

 

http://medicalxpress.com/news/2014-07-tool-potential-therapies-multiple-sclerosis.html

Innovative research tool pinpoints potential therapies for multiple sclerosis

by Pete Farley
multiple sclerosis
Demyelination by MS. The CD68 colored tissue shows several macrophages in the area of the lesion. Original scale 1:100. Credit: Marvin 101/Wikipedia
Using a novel screening platform to rapidly evaluate the cellular effects of 1,000 chemical compounds, a team led by UC San Francisco scientists has identified eight drugs that may stimulate nervous system repair in multiple sclerosis (MS).

All eight compounds have previously been approved by the U.S. Food and Drug Administration (FDA) for the treatment of other conditions. One of the most promising agents is an antihistamine, though the scientists caution that MS patients should not use the drug until clinical trials have established whether it can safely and effectively treat MS, and if it does, what the proper dosages and treatment regimens would be. Because of the drug’s emergence as a clear front-runner in the new study, a Phase 2 clinical trial to evaluate its effectiveness in MS is already underway at UCSF.

“A major unmet need in the development of therapeutics for repair in MS has been the ability to screen compounds in a high-throughput manner,” said Jonah Chan, PhD, the Debbie and Andy Rachleff Distinguished Professor of Neurology at UCSF and senior author of the new study. “Through a great deal of serendipity, combined with the hard work of outstanding students and colleagues, we have been able to address this need, and I am happy that we are already testing one compound in the clinic.”

The new research was published online July 6, 2014 in Nature Medicine.

The decision to focus on compounds already approved by the FDA was driven by study co-author Stephen L. Hauser, MD, the Robert A. Fishman Professor and chair of the Department of Neurology at UCSF. As founder and director of UCSF’s interdisciplinary MS Research Group, Hauser has championed efforts to translate insights from basic neuroscience research into new therapies as quickly as possible. The new study is an exemplar of that strategy: only 14 months have elapsed since the team performed the first drug screen, and the Phase 2 trial is already at its halfway point.

Co-author Ari Green, MD, Debbie and Andy Rachleff Distinguished Professor of Neurology, is principal investigator on the Phase 2 trial at UCSF, which is known as the ReBUILD trial. According to Green, the trial was expedited by the FDA’s granting of a New Drug Application exemption, which allows clinical researchers to study drugs in conditions for which they were not originally approved. The trial is still enrolling MS patients and is expected to be completed by the end of 2014.

In MS, the immune system goes awry and attacks myelin, a fatty sheath covering the thin nerve-cell extensions called axons that transmit signals in the brain. Much like the plastic covering on electrical wiring, myelin provides insulation that is crucial to quick, efficient communication among neurons. Poor neural conduction leads to the range of progressively worsening symptoms of MS. Myelin degeneration damages axons and ultimately causes nerve cells to die off.

Myelin is formed by specialized cells called oligodendrocytes, which wrap themselves around axons in multiple layers. This wrapping process, known as myelination, has generally been studied in combined cultures of neurons and oligodendrocytes, and until recently it was widely believed that axons provide some chemical signal to oligodendrocytes that initiates myelination.

But in 2012, Chan and colleagues published studies showing that oligodendrocytes will myelinate synthetic “nanofibers” of approximately the same diameter as axons. Though this work showed that it was possible to study myelination in oligodendrocytes alone, the configuration of the fibers used in the experiments made it difficult to automate the detection and quantification of myelination, which are essential criteria to efficiently screen drugs that might stimulate remyelination to treat MS.

To address these problems, Chan’s research group designed a new system based around precisely fabricated conical “micropillars.” Each micropillar is only a few thousandths of an inch thick at its base, and 10,000 of them can fit within a 5-millimeter-square “well.” Chan’s team created plates of 96 micropillar wells and loaded up each well with 40,000 oligodendrocyte precursor cells (OPCs), the cells from which oligodendrocytes are derived in the brain and spinal cord.

OPCs do not always differentiate into myelin-forming oligodendrocytes, so the research team tagged the cells with fluorescent markers that would glow green if the cells remained OPCs, and glow red if they had become oligodendrocytes.

The group then systematically applied 1,000 compounds from a library of FDA-approved drugs to the wells with an automated screening platform. Using a confocal microscope to view the slides from below, the researchers could quickly determine from the color of the cells if they had differentiated into oligodendrocytes, and could also calculate how thoroughly any oligodendrocytes had wrapped the micropillars—from beneath the micropillars, myelination is seen in cross-section, and quantifying it is much like counting tree rings.

In 2013, Chan was the inaugural winner of the Barancik Prize for Innovation in MS Research from the National Multiple Sclerosis Society for his work on the new platform, which is known as BIMA (Binary Indicant for Myelination Using Micropillar Arrays).

The vast majority of the compounds tested with the BIMA platform in the new study killed the OPCs or were not beneficial to their development, and many prompted the OPCs to proliferate without transforming to oligodendrocytes. But eight drugs stood out on two counts: they successfully prompted OPCs to differentiate into oligodendrocytes, and the resulting  robustly wrapped the micropillars with layers of myelin.

Remarkably, all eight drugs share a common mechanism of action: they each block a particular receptor—called the muscarinic receptor—on a subset of OPCs that respond to the neurotransmitter acetylcholine.

The antihistamine clemastine was the most effective of all 1,000 compounds tested in promoting both oligodendrocyte production and myelination. The drug exerts some of its anti-allergy effects by blocking the actions of histamine in mucous membranes, but the drug also has an “off-target” effect, blocking muscarinic receptors in the brain and elsewhere in the body.

“It is imperative that we exploit and utilize the power of our screening platform to search for additional compounds, but another next step is to identify the receptor targets of these anti-muscarinic drugs so we can develop therapeutic compounds with minimal side effects,” said Chan. “There are five different muscarinic receptors expressed in the nervous system, and a major question is whether the effects we observed are the result of blocking a single receptor or a combination of multiple receptors. Understanding the molecular mechanisms responsible for oligodendrocyte differentiation and myelination will provide valuable insight into the repair process and guide the development of new effective therapeutics for remyelination.”

 Explore further: ‘Master switch’ for myelination in human brain stem cells is identified

More information: Micropillar arrays as a high-throughput screening platform for therapeutics in multiple sclerosis, Nature Medicine, www.nature.com/nm/journal/vaop… nt/full/nm.3618.html

 

Understanding Multiple Sclerosis

http://raconteur.net/healthcare/ms-medical

 

UNDERSTANDING MULTIPLE SCLEROSIS
Danny Buckland explains multiple sclerosis in plain language, and outlines treatments on offer and in development

WHAT IS MS?

Multiple sclerosis (MS) is a neurological condition that damages the central nervous system. The body’s immune system attacks and degrades a fatty tissue coating, called myelin, that surrounds and protects the nerve fibres of the brain and spinal cord.

The term refers to the multiple areas of tissue hardening (sclerosis) that disrupt signals from the brain to all parts of the body.

The MS Society sums up the impact by likening the body’s central nervous system to the electrical supply in a home. If the wiring is faulty, lights flicker, the TV jumps channels and computers freeze. In MS, the appliances are different parts of the body that can malfunction causing pain, discomfort and disability.

Relapsing and remitting MS strikes in cycles that can be days, weeks or months apart and, although the patient can make a good recovery, each relapse can take its toll on the myelin sheath. At this stage, MS is an inflammatory condition. Over time, the majority of these patients will reach the progressive phase, which is known as secondary progressive MS, which is dominated by accumulating and irreversible disability. Some 15 per cent of people have progressive disease from the outset.

Although not fatal, it can weaken the immune system and people can die from complications related to MS. Symptoms include mental and physical fatigue, visual problems, difficulties with speech and swallowing, cognitive impairment, balance and co-ordination issues, along with muscle stiffness and pain. No two cases are the same and symptoms can vary in duration and intensity making life unpredictable.

Scientists cannot say with certainty why someone gets MS, but viruses in childhood or adolescence, a lack of vitamin D and smoking have been identified as potential triggers, and the root cause is likely to be a combination of genetic and environmental factors. It is not hereditary, but there is a heightening of risk among family members.

“We do not know for sure what causes MS, but it is a dog that keeps biting in different places at different times,” says Dr Eli Silber, a consultant neurologist and MS specialist at King’s College Hospital, London.

The random nature of its strike pattern makes it difficult for clinicians to target and, although it is manageable, MS has a major, long-term impact on lives.

MS was first described clinically in 1868, but therapy progress was slow until 20 years ago when magnetic resonance imaging (MRI) techniques allowed more accurate and swifter diagnoses, and disease-modifying treatments (DMTs) cut relapses by 30 per cent.

 

RELAPSE AND REMITTING MS

The lifeline for MS patients has been a suite of disease-modifying treatments (DMTs) taken as tablets or injections, which help neutralise the harmful cells at work during a relapse, and shore up the central nervous system to reduce the level and effect of attacks.

They are not a cure but, combined with symptom management treatments, which deal with a range of symptoms from tiredness to bladder problems, first-line treatments can reduce relapses by up to 50 per cent.

Newer drug therapies can have even better results, but they are harder for patients to get on the NHS as they are given as second-line treatments.

Patients can also boost their defensive arsenal with alternative therapies, such as acupuncture, massage, yoga, meditation and physiotherapy. Vitamin D supplements are recommended by some physicians, but as yet have not been shown to change the course of the disease.

The bleak landscape for MS patients began to change with the introduction of beta interferon in the late-1990s, an injection given every other day that lessened inflammation, although it did have flu-like side effects.

The number and potency of DMTs has continued to grow and among them are Fingolimod (Gilenya), Natalizumab (Tysabri) and Alemtuzumab (Lemtrada).

Gilenya, a daily tablet, works by binding to the surface of white blood cells in the immune system, trapping them in lymph nodes, hampering their ability to attack the central nervous system. It is generally given to patients who have failed on first-line therapies and can cut relapses by more than 50 per cent.

Tysabri, a monoclonal antibody taken as a monthly infusion, sticks to molecules on certain immune cells and stops them getting through the blood-brain barrier. It is a key treatment for more aggressive relapses.

Lemtrada, which was made available in England and Wales on the NHS in April, is given as a course of infusions annually. It kills off the cells in the immune system that mistakenly attack the myelin. When new cells are generated, they are thought to be free from the rogue element. The drug, developed by the University of Cambridge and Genzyme, resulted in far fewer relapses than in study subjects on beta-interferon injections in clinical trials.

Another great encouragement is the discovery that the brain can repair itself in remission by creating new myelin to boosts nerve protection. But the challenge is to accelerate the process for effective relapse damage repair.

MS specialist Dr Eli Silber emphasises the importance of specialist MS nurses in supporting patients with psychological issues.

 

PRIMARY AND SECONDARY PROGRESSIVE MS

Around 80 per cent of people with relapsing and remitting MS will develop the progressive form of the condition, which is where the neurodegeneration hits a downward trajectory.

There are no licensed treatments for this stage. Disease-modifying treatments (DMTs) have been trialed, but have shown only flickers of hope. The lack of effective treatments has galvanised global action and the Progressive MS Alliance, a collaboration of MS organisations, is connecting scientific programmes and awarding grants to boost research.

“There has been such an explosion of new and exciting anti-relapse DMTs that the scientific and research community can now focus more on progressive MS which we just don’t understand,” says Jeremy Chataway, a consultant neurologist at the Queen’s Square MS Centre, the National Hospital for Neurology and Neurosurgery, University College London. “There is now a global focus to this problem. We first need to slow the progression by putting in repair drugs and re-myelinating.”

Dr Chataway offered recent hope with his phase II interim results on the use of a high dose of a statin, published in The Lancet, which showed a “favourable effect on the rate of brain shrinkage” in patients taking 80mg of simvastatin, double the normal dose used to treat high cholesterol.

“It was very encouraging and exciting. We need further trials, but it is a very good step in the right direction,” he says.

Dr Chataway is running the £2.7-million MS-SMART trial that will evaluate three promising drugs in 440 patients at 15 centres in England and Scotland. The trial, funded by the Medical Research Council and the MS Society, is being run jointly with Professor Siddharthan Chandran at Edinburgh University.

Collaboration between King’s College and Imperial College London is using stem cells to test the potential of Fingolimod and Tysabri on progressive MS.

A small Phase II study by Biogen Idec, published in the journal Neurology, had recorded promise in Tysabri, reducing inflammation in progressive patients.

“A lot of the research has been in the early anti-inflammatory areas of MS,” says MS specialist Dr Eli Silber. “There needs to be more for the degenerative progressive side of the disease where we have been less successful at slowing down the process.”

Professor Chandran, who is pioneering research into how the brain can repair itself, describes progressive MS patients as “the lost tribe of MS” because of the absence of any DMTs for this phase of the disease that ultimately affects the majority of sufferers. “This is the great unmet need but there are some potential wins,” he says.

 

THE FUTURE OF MS

MS has emerged out of the dark ages and is now a “pathfinder” disease whose research could accelerate treatments for dementia, Parkinson’s disease, Huntington’s and motor neurone disease.

Solutions for the degenerative type of MS could be transferrable across other conditions, says Professor Siddharthan Chandran, director of the Centre for Clinical Brain Sciences and clinical director of the Anne Rowling Regenerative Neurology Clinic, University of Edinburgh.

It was thought that damage to the myelin was irreversible, but studies have shown the brain actually starts laying down new myelin during remission.

“It is nothing to do with doctors, it is a natural event,” says Professor Chandran. “We grew up being taught that, unlike the liver, skin and gut, for example, the brain could not repair itself, so the logic was that following injury you had no ability to repair. However, recent identification of brain stem cells challenges these assumptions.

“An example of brain stem cells in action is the laying down of new myelin which in turn is protective of damaged nerves. The problem is that it does not do it sufficiently, so our challenge is to supplement and enhance it by finding the cues to promote and accelerate brain stem cell mediated repair. The idea would then be to prescribe drugs that will mobilise your own or endogenous brain stem cells to repair the damage caused by MS.

“An alternative approach is to make human brain stem cells in a ‘dish’ in the lab and then parachute these into the injured MS brain. My view is that mobilising our own brain stem cells using drugs is likely to be the future and most cost-effective method to promote repair in MS.”

He adds: “In the next five to ten years, there will be huge advances in therapeutic trials where you are testing drugs predicted to promote the brain’s own capacity to repair itself.

“I don’t want to fuel false hope, but I am optimistic we will make inroads in the medium term which will give us a window into progressive MS as well as other degenerative disease including the dementias.”

The buoyant research field includes more than 6,000 patients being enrolled on clinical trials into progressive MS over the next five years. And an early-stage study at the University of Utah in the United States has shown that treatment with human stem cells can enable mice crippled with a form of MS to walk again.

“Everyone is trying their best to see if we can get a chink of light,” concludes consultant neurologist Dr Jeremy Chataway. “It would be good to have something, even if it’s not much to start with.”
Written by Danny Buckland
Award-winning health journalist, he writes for national newspapers and magazines, and blogs about health innovation and technology.