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NEUR2201Multiple Sclerosis














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MSIntroduction


Multiple Sclerosis is widely known as MS, which is a disease that affects the Central Nervous System (CNS). The central nervous system is composed of the brain, the spinal cord and the optic nerve. About 2 500 000 people around the world have been diagnosed with it and 18 000 people in Australia are suffering from this uncontrollable disease.

The video above first broadcasted on CNN in 2008. It reveals a few of the many symptoms Multiple Sclerosis patients suffer from and introduces a drug found in their latest research. Up until now there is still no cure for MS, however there are a range of drugs and alternate types of treatments which can help to minimise symptoms of MS as well as the number of MS attacks.
The video is presenting a drug called Alemtuzumab, the scientific name for Campath. It is said to help patients by improving their symptoms as well as helping to reverse the disease process. However this drug is not suitable for people with advanced forms of MS and may cause some serious side effects.
With so many people dealing with this disease, in different forms and severity, we chose this video due to the interviews conducted and research, it provided a real sense of hope in helping deal with the hardships many people experience living with Multiple Sclerosis.



MSNeuroscientific Context



Immunopathenogenic Processes


Multiple Sclerosis is a disease characterised by its progressive and chronic axonal damage via demyelination throughout the central nervous system. The autoimmune attack of axons in the grey matter (and in particular the white matter) cause crippling global neurological deficits over time. MS is typically more prevalent in adolescence and generally has a relapsing/remitting progression after an initial onset of demyelination called Clinically Labelled Isolated (Gold & Wolinsky, 2011). The causation of MS is unknown, current theories speculate causal inferences from a complex interplay of environmental and hereditary predisposition or even viral pathogens causing a marked change in autoimmune response (Hemmer & Archelos, 2002). Due to the mysterious causation of the disease, early diagnosis may be difficult and in many cases only be achieved by the close analysis of patient behaviour (especially ataxia), physical abnormalities such as white matter lesions and inflammation and other symptomatic criterion such as severe fatigue and weakness of the lower extremities. It is important to note that multiple pathogens, which do not pertain to MS, may cause axonal demyelination and white matter lesions; hence a temporal analysis of the diseases progression is imperative (Gold & Wolinsky, 2011).


Auto-reactive myelin specific T cells, which are produced in the peripheral immune system, are triggered into attacking the body’s own CNS. Primarily, these cells are able to transcend through the blood brain barrier, which is comprised of tight, endothelial cells which selectively diffuse hydrophobic molecules and utilise active transport to carry molecules such as glucose. The T cells bind to the specialized capillary epithelial cells and produce chemicals such as tumour necrosis factor to pry open the blood brain barrier and enter the CNS to acutely attack its target, myelin on the axons in neurons in both the white matter and grey matter. Once inside the CNS, these T cells are able to recruit further CNS inflammatory antigens (Frohman, Racke & Raine, 2006; Wu & Alvarez, 2011).

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It is important to note that demyelination of the axon does not only result in a loss of conduction but also reduced excitability, reduced axonal support, destabilised membrane potentials of the axon and the redistribution of ion channels. Mechanisms for demyelination include toxins that are produced by the invading auto-immune cells. One such example is excitotoxicity, where excess glutamate stimulates the increase in AMPA and NMDA gate channel activation (Awad & Stüve, 2010). This causes an influx of calcium which destroys mitochondria in the oligodendrocyte. The oligodendrocyte is responsible for wrapping around axons and hence becoming myelin which vastly improves neuronal conduction. As the oligodendrocyte is damaged, the myelin also becomes damaged and is subsequently phagocytised by the astrocytes and marcrophages recruited by autoimmune T cells which originally crossed the blood brain barrier (Frohman, Racke & Raine, 2006).


multiple-sclerosis-and-stem-cell-treatment.jpg
figure 1: show how the damaged Myelin exposed nerve






MSTreatments



Medical Treatments


Immunotherapy, there are a range of drugs currently available for MS sufferers that focuses on controlling the immune response of the patient to preventing further damage to the myelin. There are a few different types of drugs that can do this:

Interferon beta-1a

Interferon beta-1a is derived from mammalian cells which are believed to have anti-inflammatory properties (Lawrence, 2000). Its effects on Multiple Sclerosis patients include reduced inflammation of the myelin which is a major problem causing lesions and plaques. It can also help maintain the quality of the blood brain barrier, preventing its break down which would lead to substances from the blood traveling to the brain which could be detrimental (Lawrence, 2000). Studies have shown that INFR beta-1a can result in an 18 to 36% reduction in relapses in patients. There are some adverse side effects such as flue like symptoms shortly after commencing the treatment, depression and anomalies in the blood. More severe effects include seizures and damage to liver function (Lawrence, 2008). Some commercial forms of this drug that are available are Avonex and Rebif.

Alemtuzumab (Lemtrada or Campath)

Most commonly used to treat patients with leukemia, it has been sown in recent studies that Alemtuzumab, when implemented early in the progression of MS, can reduce damage to the myelin and may even reverse the diseases effects (Jones, 2010). The drug is a monoclonal antibody that works by targeting CD52 proteins that are on the surface lymphocytes preventing them from attacking the myelin in the central nervous system (Jones, 2010). Alemtuzumab may also have some anti-inflammatory effects (Jones, 2010). The improvement of the drug is most effective for those who have relapsing-remitting MS and only if it is treated early enough. Alemtuzumab also has negative side effects for the patient, commonly resulting in autoimmune diseases such as thyroid disorders, infections and immune thrombocylopemic purpura (Cossburn, 2011). The drug is still being clinically tested for its effectiveness in treating Ms.

Alemtuzumab vs. Interferon beta-1a

Studies have compared the effectiveness of these two drugs in treating Multiple Sclerosis. Alemtuzumab has shown to reduce disability far more successfully than INFR beta-1a, which in some cases has increased disability, the results have shown an increase in brain size for those who had taken Alemtuzumab as for the patients who were treated with INFR beta-1a there was, in some cases, had a slight decrease in brain size, these results were seen over a period of 36 months (Coles, 2008) (see figure 2.). The main comparison for these two drugs has been carried out by the CAMMS trial investigators who tested Alemtuzumab, using 3 groups of patients, each given a different treatment, one receiving 12mg of Alemtuzumab and another receiving 24mg. The third group received INFR beta-1a (Coles, 2008). The multiple sclerosis patients used for the study had relapsing-remitting MS in its early stage. The Alemtuzumab therapy had to be discontinued part way into the study due to some patients developing immune thrombocylopemic purpura which resulted in one death, INFR beta-1a was still continued. The results obtained showed that Alemtuzumab was more effective than INFR beta-1a, having a higher rate of reducing disability by 26.2% compared with INFR beta-1a 9%, the different doses of Alemtuzumab showed no difference in results.. Alemtuzumab also had
a lower relapse rate, however is associated with autoimmune diseases (Cossburn, 2011).


alemtuzumab_ms.jpg
Figure 2. Relapse rate of disease comapred with INFR beta-1a and Alemtuzumab

Alternate therapies


Based off of information obtained from MS Australia (MS Society), there are a range of alternate therapies available that may reduce the symptoms of ms, however many of them are not scientifically proven and are recommended based on the individuals openness to these therapies. There is a wide variety of therapies available that include acupuncture, massage, yoga, meditation and some other subtle approaches.

Acupuncture is formed from ancient Chinese medicine. It is believed that by inserting special acupuncture needles into specific points on the body allows to clear chi (energy of life) blockages. For MS sufferers it's used to reduce muscle spasms and pain which help manage the symptoms. It is not known, scientifically, how acupuncture works, however it is still an effecting treatment.

Massage is a good tool to sooth and relax muscles due to the vast amount of nerve endings that are contained within the skin which helps relieve symptoms.

Yoga is another useful therapy for alleviating symptoms. It focuses on body positing and breathing. The poses cause gentle stretching of muscles which reduce stiffness. Overall yoga reduces stress and tension, often through meditation. Mediation is used to relax and de-stress the patient by "clearing ones mind". It has been observed that during meditation the brain produces alpha waves causing a relaxation of the nervous system.

Other alternate approaches that try to alleviate MS symptoms include removing mercury dental fillings due to the idea that mercury poisoning in the body can cause MS symptoms. There is also Hyperbaric Oxygen Therapy and, with no proven benefit so far, Nutritional approaches such as change in diet and use of vitamin supplements.


MSCritical Analysis



This broadcast item is a report originally from ITN, Independent Television News, but broadcast on CNN, a 24 hour US cable cable news program. Both watermarks of ITN and CNN are on the video.

The purpose of this segment is to show breaking news in the research of the treatment of Multiple Sclerosis to bring good news and how it can affect those living with the symptoms and help them with their everyday lives.

This video was broadcast more than two years ago, therefore current medical research has excelled since then. The drug mentioned in this video still has not been approved as a drug used to treat MS patients and is still being tested. Its prospects maybe replaced in the future by other drugs that are found to be more effective with less side effects.

Renowned medical editor Lawrence McGinty, ITN Medical Director has reported this segment. His reputation as a reporter is extensive and analytical on a broad range of issues such as science, medical and environmental issues. Holding the "anonymous looking liquid" in his fingers he states that it "seems to be the first drug", noting that it is not certain that this drug is not the definite solution.

He interviews a number of people to investigate further into the drug, how it affects people and what it is actually doing for people with Multiple Sclerosis. The beginning of the video goes straight to a woman describing her symptoms as a patient of Multiple Sclerosis. This allows people watching at home, who may suffer from similar symptoms, to relate and therefore engage the audience to further watch the video in hope of a treatment. Following the woman's interview, and how successful she was with the drug, there are diagrams to help demonstrate the effect of Alemtuzumab. This diagram is further explained and confirmed by an interview with Professor Alastair Compston from Cambridge University. Cambridge University is one of the top ranking universities in the world with a high reputation. With this interview, viewers at home would more likely to believe this information from a reputable person. The woman that was interviewed in the beginning was an older woman, so the segment interviewed a second woman, this time a younger woman demonstrating that Multiple Sclerosis can affect people in a wide range of ages. Towards the end of the video, McGinty states that "it's not a cure, but it's "early days" and that it could give a "brighter future".

Since CNN is a 24 hour news program, and this segment the target audience for this particular video would come under the people who watch this show during the middle of the day, more specific towards older people who stay at home. This information would then be relayed to relatives or friends that are currently diagnosed with Multiple Sclerosis. There is an aspect of this video that must be taken with caution for viewers at home who wish to be informed, which is that the segment is biased, portraying a positive image for Alemtuzumab. From the research that has been conducted, there has been strong support for the effectiveness of the drug, but also strong evidence that the drug can cause severe side effects in the for of autoimmune diseases, which is only implied subtly once during the program. This negative side to the drug must be acknowledged and taken seriously as it can have drastic consequences in some cases.

This video was broadcast more than two years ago, therefore current medical research has excelled since then. The drug mentioned in this video may have been overridden with more advanced and newer technologies which may help to treat Multiple Sclerosis.




MSResearch Strategy



Neuroscience is such a broad subject which involves many interesting aspects, and therefore it is difficult to pick one topic as a group to work with. After many discussions about what topic we should work with, our group decided to do research on Multiple Sclerosis, as we all heard of this disease but none of us knew what the disease was and what harm it caused to the patients.


We all went out and searched for an interesting media item that talked about the disease, when the deadline was near we had to decide on an item, so we originally picked a YouTube video which is a documentary about the treatments of MS in general, however a few days after we got the approval from Dr Vickery we found that the video had been removed and we no longer had access to it, so we quickly resolved this problem by finding a similar video which talked about the new drug called Alemtuzumab. Once again we sought approval and it was granted to us. This time we didn’t want the same thing to happen so we downloaded the video for safe keeping.


We decided to pick this particular video as it was more a news report which set out to inform people of this new finding. The video was posted in 2008, which at the time this drug was still on trial; therefore we wanted to see if it had been approved in the past three years. We chose this news segment rather than an advertisement from another drug company as it contains interviews of people from the field of research rather than just amateurs.

References



Awad, A.M. & Stüve, O. (2010). Immunopathogenisis of Multiple Sclerosis. New Insights and Therapeutic Implications. Continuum Life Long Learning in Neurology. 5. 166-180.

Coles, A. J. (2008) Alemtuzumab vs. Interferon beta-1a in early multiple sclerosis, New England Journal of Medicine, vol.359(17), p.1786-1801.

Cossburn, M. (2011) Autoimmune disease after Alemtuzumab treatment for multiple sclerosis in a multicenter cohort, Neurology, vol. 77(6), p.573-579.


Frohman, E. M., Racke M. K. & Raine, C. S. (2006). Multiple sclerosis–the

plaque and its pathogenesis. New England Journal of Medicine. 354. 942–

955.

Gold, R., & Wolinsky, J. S. (2011). Pathophysiology of multiple sclerosis and the
place of teriflunomide. Acta Neurologica Scandinavica. 124. 75 – 78.


Hemmer, B., Archelos, J. J. & Hartung, H. (2002). New Concepts in the Immunopathogenisis of Multiple Sclerosis. Nature Reviews Neuroscience. 4. 291-301.

Jones, J. L. (2010) Improvement in disability after Alemtuzumab treatment of multiple sclerosis is associated with neuroprotective autoimmunity, Brain, vol.133(8), p.2232-2247.


Lawrence, D. (2000) Intramuscular Interferon Beta-1A Therapy Initiated during a First Demyelinating Event in Multiple Sclerosis, New England Journal of Medicine, vol. 343, p.898-904.

Information obtained from MS Societywho obatined their information from The Better Health Channel (2001). MS Society also used information from: Sibley, W. A. (1996) Theraputic claims in Multiple Sclerosis, International Multiple Sclerosis Societies 4th edition.

Wu, G. F. & Alvarez, E. (2011).The Immunopathophysiology
of Multiple Sclerosis. Neurologic Clinics 29. 2. 257.

Figure 2. obtained from: http://ryo1m.cocolog-nifty.com/blog/2008/10/alemtuzumab-in-.html

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