Treatments For Multiple Sclerosis Biology Essay

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Multiple sclerosis is disease which mostly affects young adults and twice the men, women gets affected, the exact cause is unknown but it is caused when the myelin covering nerve fibre gets damaged in CNS the basic movements in daily life gets effected, treatment for this disease is not permanent and all the present treatments and drugs such as interferon beta-1a, interferon beta-1b are disease modifying which controls the attack but cannot cure and corticosteroids are used to treat the relapses in severe cases, all these drugs have high side effects moderate efficacy, many new promising therapies like combinational therapy, novel oral drugs are in ongoing clinical trials which are hope for the people suffering with multiple sclerosis.

Multiple sclerosis (MS) is a chronic, disabling neurological disease that affects conduction of nerve impulses of the central nervous system integrated with the brain, spinal cord, optic nerves. Myelin sheet the fatty substance that protects the nerve fibers by surrounding it in the central nervous system is damaged. The exact cause is not known yet but it is considered as autoimmune disease by the doctors. The progress, severity, specific symptom of MS is unpredictable and different from one another. New hope to people affected by the MS is given by new treatment and advances in research. (1)

Types of MS

Though the damage of nerve is common in all the people suffering with MS, it is classified by the progress, severity and specific symptom in each individual by the researchers and doctors.

Primary Progressive Multiple Sclerosis (PPMS)

In this type of MS there are no well-defined attacks, the symptoms get continuously worsen from the beginning and there is little or no chances of recovery in 10% to 15% of people.

The aspects which distinguish primary progressive MS from others are

Primary progressive MS is mostly diagnosed at the age of 40.

It is developed approximately equal in men and women.

It usually leads to disability.

The response to treatment is poor, although studies are ongoing but no treatment has been helpful.

Relapsing-Remitting MS (RRMS)

In this type of MS people experience clearly defined attacks, these are periodic and called as relapses, which is followed by partial or complete recovery periods called as remitting , during which no disease progression occurs.

85% to 90% of people with MS suffer with relapsing-remitting type

Most people in early 20 will witness their first affects.

Twice than men, women suffer with this type of MS and most people will enter a secondary progressive phase of MS.

Secondary Progressive MS

After suffering with relapsing-remitting MS people develop secondary progressive MS.

In this type the symptoms get steady without relapses or remission, the translation to secondary progressive MS takes 10 to 20 years after relapsing remitting type is diagnosed.

It is unclear why the transformation occurs and why most people with incomplete recovery from relapsing-remitting generally convert to secondary progressive MS faster than others, less inflammation and slow degeneration of nerves.

Treatment for this type of MS is challenging as the progression occurs at different rate in each person and leads to disability.

Progressive relapsing MS

It is the least common MS of all in which relapses or attacks occur periodically but symptoms continue to progress in between relapses. It is rare and around 5% of people with MS have this form. (2)

Symptoms of multiple sclerosis 

As the nerve fibers that impulse to and from brain and spinal cord are damaged the symptoms vary in different people.

The most common symptoms are:

Visual problems

Inflammation of the optic nerve can cause optic neuritis to one eye, pain behind eyeball, loss of vision and colour blindness.

Muscle Spasms and spasticity

The muscles get contract tightly and painful (spasm) and muscles may also become stiff and resistant to movement (spasticity).

Cognitive problems

The thinking and learning processes such as remembering and learning new things gets affected for temporary or permanent, problems with attention and concentration slowed or confused speech occur. These symptoms occur when MS is severe.

Emotional Problems

People suffering with MS may be found laughing or crying for no reason and may experience depression or anxiety.

Fatigue and tiredness

The main symptom in people suffering with MS is extreme tiredness, which causes other problems with balance e, vision and concentration to get worse.

Bladder problem

The bladder may contract and behave overactive and underactive, which cause problem in urine flow.

Bowel problems

Often multiple sclerosis causes constipation and bowel incontinence. (3)

Diagnosis

Diagnosing multiple sclerosis is very though task as the symptoms vary from person to person and time to time in each individual and in some individuals no symptoms are shown, there is no single test can confirm the disease.

To confirm the disease series of test are conducted.

Several strategies are used to determine disease in a person, evidence of damage of at least two separate areas in CNS and the damage occurred at least one month interval can be confirm.

(MRI) Magnetic resonance imaging scan

MRI scan is a painless procedure usually done for 10 to 30 minutes and shows the detailed image of the brain and spinal cord by which the damage or scaring of myelin in CNS can be known.

Evoked potentials test

In this test electrodes are placed on the patient's head, and monitor the brain waves responding to the patients hearing and vision. It shows if the brain is getting messages at longer time.

Cerebrospinal fluid Analyses

Sample of cerebrospinal fluid from spinal tap is analyzed to detect the levels of proteins in immune system and presence of oligoclonal bands, which indicate an immune response with CNS in 90- 95% of people with MS. As these bands are present in other diseases it cannot be relied as positive.(1)

Treatment

Development of therapies of MS

Jean-Martin charcot , was the first person to find the definite links between the symptoms of MS and pathological changes seen in post-mortem sample and described it as sclerosis.(4)

Corticosteroids were the first drugs tried to treat the relapses symptom in 1960's followed by variety of immune suppressing agents like cyclophosphamide, cyuclosporine, azathioprine, methotrexate and glatiramer acetate. (5) These drugs were not effective to reducing the symptoms but made useful platform for the developing tools for further studies in immunomodulation and explored the development of non-invasive monitoring methods in 1980's.(4)

The Launch of Magnet resonance imaging (MRI) made easy to visualise the brain and spinal cord to quantify the lesions in people suffering with MS. (4) Ian Young had predicted the value and suggested that MRI technique will help to measure the condition of MS and tried to evaluate the therapeutic regimens effect on MS.(6) In 1986 Robert Grossmann improved the MRI technique and discovered gadolinium enhancement as a marker of inflammation to detect the newly formed lesions.(7) And MRI technique was established for monitoring disease prognosis in clinical trials.

Interferons have been used in the history of developing drugs for the studies of man preceded animal studies. Interferon gamma can provoke accurate exacerbation of multiple sclerosis was found in early clinical trials, but was not show much important in treatment because of severe side effects, then interferon beta came in light as they can inhibit interferon gamma and they were well tolerated compared to interferon alpha. The importance of interferon beta came to publication in 1993 and was started to use as therapy, and was introduced in the form of interferon beta -1b in USA as the first proven effective therapy for relapsing remitting MS (8,9), and showed that they can be used for the treatment of secondary progressive MS in a study conducted in Europe(10).

New ways of finding therapies

The studies in the treatment of MS was challenging as many promising agents failed in the experimental treatments. But the classification of MS in to different forms played important effect in clinical trials conducted for MS. The trials were included blinding, randomisation, and selection of subjects made better outcome. (11).

Present day treatments

The present day treatments are managed to give individually or combined to the patents for effective results. They are classified and given as per the symptoms of the patents to reduce the symptoms or to modify the disease course.

1. Disease modifying agents.

Disease modify agents reduce the progression of the disease activity in people relapsing from MS and people with SPMS disease.

FDA approved drugs for modifying disease course

Interferon beta-1a is avlable in different names like Avonex, Rebif.

Interferon beta-1b is avlable as Betaseron, Extavia.

And mitoxantrone as Novantrone, fingolimod as Gilenya are used

2. Treating Exacerbation

When the disease is sever and attack last for more than 25 hours to week and impacting the ability to do basic functions then high dose of Corticosteroids are used to decrease the inflammation.

Corticosteroids used for treating MS

methylprednisolone (Solu-Medrol),

dexamethasone (Decadron)

3. Managing symptoms

Symptoms of MS are different at time to time in one person and vary in each individual from mild to severe and they are managed mostly by strategies by proper medication, rehabitation of speech/language and using assistive devices.

Complementary and Alternative ways of treating MS

Many complementary and alternative ways are used by many people suffering with MS like dietary supplements, acupuncture, yoga which is from different traditions. These ways or medications do not have any scientific studies but still many people believe in them.(1)

All the present day drugs have high side effects and moderate efficacy, they are all disease modifying drugs and are not adorable by patents as they are injections, which causes pain. So patients are hoping for novel drugs which can give them better results.

Prospective treatments

There are many drugs in the clinical trials stage which can give a better support to improve the symptom of the people suffering with multiple sclerosis.

Combination therapy

All the present available drugs are well tolerated but the effect of the drugs are for very limited period. The strategies for better efficacy are being made one of which is combination therapy. Several results of combination therapy have been published recently and many are still ongoing.(12)

Combinational therapy in treating many other chronic diseases like cancer, immune disorders like rheumatoid arthritis and hypertension have been proved very effective (13). The study on combined therapy of methotrexate and adalimumab for rheumatoid arthritis has made the therapy stranded for rheumatoid and for other tissue damaged conditions. (14) .studies in combination therapy using corticosteroids have been made, they have large impact on immunological conditions and as corticosteroids are used to treat in recovery of relapse condition MS the combination of them to treat MS will be very effective. (15)(16)

The combinational therapy is very intresting and shows positive hope for MS patents but the studies has to more specific to know the inter-action of the drugs which are been combined to treat as the they may have long delay effects.

New oral drugs

Many promising oral drugs are in trial stages which have potential to treat people with MS more effective than the present drugs

Fingolimod

Fingolimod is a oral drug with a novel mechanism, which is currently in a phase III study, in phase II study, half year of the study in 281 patients with RRMS given orally with doses of 1.25.and 5 mg reduced inflammatory activity significantly when measured by MRI and clinical relapses. The reduction in activity showed 80% compared to patients on placebo, and showed 50% in 6-moth annualized relapses rate at two doses 0.35-0.36 compared to 0.77 with placebo. (17) The placebo controlled subjects entered the dose dose-blinded for 18-months phase and subjects treated with fingolimod were continued with treatment. The common side effects were dose dependent transient arrhythmias in a hour of first dose, increased arterial blood pressure and breathing problems.

The positive results made fingolimod in to further studies as an oral treatment option with assessing the afficacy for dose of 1.25 mg and alower dose of 0.5 mg in currently ongoing Phase III studies. (17)

Fumaric acid

The mechanism of action of fumaric acid (FA) is and how it exerts its effects is no known but it helps to deviate the induction of immune, by the deviation of interferon gamma producing autoantigen-specific Th 1 cells into an Interleukin-4 dominated Th2 phenotype. (18)(19)

Fumaric acid's most common adverse effect in Phase I clinical trial were flushing, pruitus, gastrointestinal disturbance, myalgia, dizziness and headache.

Study in 257 RRMS patients with placebo controlled double blind, randomised phase II was conducted, the first year study was planed in two phases, a 24-week,double-blind, placebo-controlled, to know safety and efficacy and followed by 24 week, dose blind, safety extension phase. The subjects who recived placebo has been given active drug in second phase, a 69% reduction in mean number of lesions has been found in patents given 240 mg TID of FA compared to patents given placebo, And 48% reduction showed when measured in MRI. Although the study was not evaluate the effects of FA but it showed the efficacy in end points to treat annualized relapses rate .(20)

The most common adverse effects were headache, diarrhoea, upper abdominal pain and hot flush.

Some more promising drugs like cladribine, teriflunomide, laquinimod are in undergoing studies, but the fate of these drugs mainly depends on the safety profile to make in to first line of drugs.

Conclusion

Multiple sclerosis is disease with varying symptoms in each individual patient. It is an inflammatory disorder of brain and spinal cord in which lymphocytic infiltration leads to damage of myelin. The diagnosis of multiple sclerosis is a though task and has to be confirmed by conducting series of test. After many studies and research for treating has been done and still many studies are ongoing to treat MS, all the present day treatments and drugs are not for permanent cure and they are disease modifying drugs which controls or delay the attacks but they do not cure the disease, they are all injections which are not adorable by patients. They have moderate efficacy which last for very less time and have more side effects. Many promising therapies like combinational therapy oral drugs are under study which can make changes to present situation of the disease and give more effective treatment and fewer side effects and easy to admin.

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