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  • Writer's pictureSBE VIT

Demyelination to Remyelination




Modern era witnesses greater challenges to human community in the form of fishy, emerging diseases. Though, the existing list is very vast with complex terminologies, one of the most deadly diseases posing a huge threat to the human community is Multiple Sclerosis.


According to a study published in the journal Neurology in 2019, Multiple Sclerosis is estimated to affect more than 1 million people in the U.S. and more than 2.5 million people worldwide in the near future. The exact reasons why Multiple Sclerosis is in limelight of this article is that it is a deadly autoimmune disorder for which diagnosis and causes still remain as unsolved mysteries.

In scientific and factual terms, Multiple Sclerosis is a long-lasting disease that affects the brain, spinal cord and the optic nerves of the eyes and can cause problems with the vision, balance, muscle control and basic body functions. The symptoms vary from person to person and treatments are devised based on the symptoms’ severity. The pathetic damage induced by Multiple Sclerosis is that the brain refrains from sending accurate signals for maintaining body’s metabolism. Despite the challenges mentioned above, it is also evident that there are other health conditions whose symptoms mimic that of Multiple Sclerosis and lead to greater possibility of misdiagnosis.


The major target for Multiple Sclerosis is myelin which is a fatty substance that covers the nerves in the brain and the spinal cord. Thus, myelin is an insulating material that wraps the axons with support cells called oligodendrocytes (a type of glial cells). The major purpose of myelin is to provide appropriate insulation for efficient transmission of electrical signals through the axon of the neuron (just like the plastic wrapping for our electrical wires). Without myelin, the nerves get damaged resulting in failure of signal communication. It is also predicted that the chances of developing Multiple Sclerosis also increases with pre-existing autoimmune conditions such as inflammatory bowel disease, thyroid disease and type-1 diabetes.


Doubts were also raised in context to triggering of Multiple Sclerosis by two viruses of the herpes family. These were raised due to similarities in the proteins found in the spinal fluid of a person infected with Multiple Sclerosis and the person affected by a neural disease caused by the virus. According to recent surveys and studies, nearly 85% of the cases have developed Relapsing-Remitting Multiple Sclerosis wherein the patients start revealing symptoms in their early 20s. After that they have attack of symptoms (Relapses) followed by periodic recoveries ranging from days to years (Remissions). After years of struggle with relapsing-remitting multiple sclerosis, the patients develop Secondary Progressive Multiple Sclerosis. In this type, the symptoms approach a steady march without relapses and remissions. This stage is witnessed usually after 10-20 years of struggle with relapsing-remitting Multiple Sclerosis. The eventual deadly type of multiple sclerosis is the Primary Progressive Multiple Sclerosis where the disease gets worsened with no well-defined symptoms (relapses) and with little or no remissions. This is also referred to as progressive relapsing multiple sclerosis.


Diagnosis:


With recent advancements in Science and technology, present-day situation witnesses great inventions in tools for diagnosis. The list includes:

  • Magnetic Resonance Imaging (MRI): helps to detect changes in the brain and spinal cord like signs of inflammation.

  • Lumbar Puncture: Also referred to as spinal tap, it checks the fluid of the spinal column. It helps to detect the proteins and related substances that serve as the signs of the disease.

  • Evoked Potentials: These are electric nerve tests that serve as confirmation for whether multiple sclerosis had affected parts of the brain responsible for vision, hearing and sense of touch.

Remarkable breakthroughs have also occurred for treating Multiple sclerosis.

Disease Modifying Drugs:


These work by curbing the immune system so that the Demyelination (destruction of myelin) is prevented. Some of the notable drugs are:

  • Beta-interferons (Interferon beta-1a (Avonex, Rebif), Interferon beta-1b (Betaseron, extavia), Peginterferon beta-1a (Plegridy))

  • Cladribrine (Mavenclad)

  • Dimethyl fumarate (Tecfidera)

  • Diroximelfumarate(Vumerity)

  • Fingolimod (Gilenya)

The treating flares also include intake of steroids. The high-dose steroids are injected intravenously or orally. However, they will not slow down the course of the disease. Alternatively, plasma exchange can be employed in case of failure in response to steroids. After plasma separation from blood, the cells are mixed with a protein solution and then injected back into the body.


Remyelination:


One of the most recent efforts taken by the scientific community to treat Multiple sclerosis is the concept of Remyelination.

Scientists are working on ways to nudge immature oligodendrocytes to become mature, myelin producing cells. Scientists work with micro-pillar arrays to test various suspected compounds that will help oligodendrocytes to grow and wrap around the cones in the same way they wrap around the axons. Scientists have identified a cluster Kappa-Opioid Receptor (KOR) as a therapeutic target for oligodendrocyte remyelination. Through this, scientists had an opportunity to provide insight into the cell autonomous mechanisms for remyelination.

The identified KOR antagonists were validated in purified rat oligodendroglial cultures to promote oligodendrocyte differentiation and remyelination. The compound U-50488 proved to be very effective for differentiation and myelination. The U-50488 treatment accelerated the kinetics of remyelination in vivo after focal demyelination with Lysolecithin. This method provides a promising future for treating Multiple sclerosis.


Thus, a disease that was once viewed with a perspective of impossible remission has started giving greater hopes to patients!


- written by S U Vandhana

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