What causes multiple sclerosis?

To be able to create a genome that will help cure multiple sclerosis we need to be able to understand what causes it, this will allow us to understand what we are trying to prevent. Once we have an idea of what causes it we can make our genome personalised to target that one factor rather than trial and error.

An immune response damages the nerve fibres that send messages to and from the brain. It isn’t known what actually stimulates this immune response in the first place but scientists believe that it is the combination of a lot of different factors combined including environmental, infectious and genetic factors.

Environmental response

  • Scientists have realised that MS mostly affects areas that are further from the equator so are researching into possible variations in lifestyle that may cause this. Evidence has suggested that a person’s exposure to vitamin D from the sun plays an important role in them developing MS. People who live close to the equator come into contact with sunlight during most of the year this means that their body makes their own vitamin D naturally supporting the immune system, this could be the reason why they are more protected against MS than people who live further from the equator.
  • Studies have shown that the more a person smokes the higher risk they have of developing multiple sclerosis and a higher rate at which the MS will evolve.

Infectious response

  • It is quite possible that some sort of infectious agent may have a part in triggering MS. A lot of these different agents have been investigated to determine if they have a part in the development of multiple sclerosis yet no definite proof has been gained to confirm it.

Genetic response

  • It is believed that if your close family have MS your chance of developing MS will increase drastically, this is because some families have been found where there is more than one person with MS
  • Also, recent research has shown that populations with certain genes in common have high MS rates within them
  • A common theory developed states that a person will be born with a genetic predisposition to react with some sort of environmental agent when they come into contact with this environmental agent it causes a response from the immune system leading to MS

 

Many people say that only the genetic factor causes MS however recent research has shown that even the identical twin of someone (They share really similar genes) only has a 1 in 4 chance of developing MS meaning there are other factors that are involved in triggering the disease.

This means that it would be hard to develop a genome to target MS as so many factors come into play so rather than thinking of a way to stop the initial immune response it would make more sense to stop the response from getting past the myelin to the nerves in some way.

 

References;

http://www.webmd.boots.com/a-to-z-guides/multiple-sclerosis-causes

http://www.nationalmssociety.org/What-is-MS/What-Causes-MS

http://www.nhs.uk/Conditions/Multiple-sclerosis/Pages/Causes.aspx

 

By Sonia and Riya

What is MS?

Multiple sclerosis (MS) is the most common neurological disease. About one in a 1,000 people are affected.

MS is a disease that targets the central nervous system- brain and spinal cord. Messages from the brain travel down the spinal cord and to muscles in the body and limbs. Messages also travel back to the brain up to the spinal cord. These messages are sent along the nerves as electrical impulses. Some tell muscles to move and control how they work together. Other nerves alert the brain to sensations such as pain and temperature.

Nerves are protected by a fatty, insulating substance called myelin. People with MS have damaged myelin. This causes electrical impulses to be blocked in different parts of the brain, spinal cord and nerves. This “insulation” breaks down in the process of demyelination so that the associated neuron becomes dysfunctional. This process can occur anywhere in the nervous system.

Why this demyelination occurs is more of a puzzle. What we do know for sure is that MS is an autoimmune disease that, for some reason, our body fails to recognise the myelin as its own and so starts destroying it.

There seem to be two main broad types of a pattern of lesions: a form that affects the spine and is usually associated with a greater physical disability and a form that affects the brain and leads to a greater cognitive impairment.

The early symptoms of MS occur when nerves are unable to carry their signals effectively. These include:

  • Weakness of limbs especially of legs
  • Numbness and “pins and needles”
  • Loss of balance
  • Loss of vision
  • Severe fatigue

Other common early symptoms include optic neuritis (inflammation of the optic nerve leading to blurred vision, loss of acuity and pain), double vision and urgency to urinate.

There are also prominent effects on memory with an impaired ability to learn and recall and more rapid forgetting with interference, with recognition less affected than recall. MS patients also have disturbances of mood. Depression is common with MS patients and suicide risk is up by 15%.

Patients with advanced cases may be dependent on a wheelchair or special seating system, produce staccato and slurred speech that may be very difficult to understand, have abnormal eye movements, upper limb weakness and ataxia, severe spastic paraplegia with spasms, and sensory loss, and be double incontinent. They may be completely dependent for all their physical care.

Unlike other diseases the symptoms of MS are unpredictable, they are different for every person with the disease. In mild cases, a person may just have intense tiredness or in severe cases become paralysed.

 

Reference:

– Need to know Multiple Sclerosis, Alexander Burnfield, 2004, page 6,7,16,17, 18,19 

– Introduction to Neuropsychology second edition, J. Graham Beaumont, 2008, page 160-162

 

By Sonia and Riya 

Why did we choose MS?

MS is one of the most common neurological disorders and currently has no cure so we decided MS might be an appropriate genetic disorder to focus on. It’s estimated that there are more than 100,000 people diagnosed with MS in the UK. If we find a cure for MS it would reduce the amount of people going to the hospital for treatment and it will improve the quality of life of many. MS is an autoimmune disorder so the body starts seeing healthy body cells as foreign and starts attacking them. MS specifically targets the lining of the nerves called the myelin sheath, which causes damage to the underlying neuron. This can slow the electrical messages being sent across the nerves and have a lot of negative implications on the body. We were thinking of producing a genome which can somehow produce a constant supply of myelin to the nerves which replaces the myelin broken down by the immune system. If a constant supply of myelin is delivered then the underlying neuron will be protected and this will prevent the patients’ symptoms from worsening and will hopefully cure patients on the long run. So as a group, we decided that this was the path to go for as we had so many different ideas for genomes for MS, and everyone took an active interest leading to a mutual agreement in committing to MS.

 

By Sonia and Riya

Research- what genetic disease to choose

This blog post includes a summary of the different genetic disorders our group discussed in an attempt to finalise one disorder that we can focus on properly. We all had many different ideas but these are some of the main ones that we felt were in need of some sort of cure the most.

Synaesthesia- Synesthesia is a condition where a sensation in one of the senses, such as hearing, triggers a sensation in another, such as taste. It intertwines the senses, so a seeing certain object could stimulate a certain taste.

Lysosomal storage diseases – Inherited metabolic diseases that are characterised by the irregular build-up of a lot of different toxic materials in the body’s cells as a result of enzyme deficiencies. It has an effect on different parts of the body including the skeleton, brain heart etc. No approved treatment for lysosomal storage disease even though there are many clinical trials.

Mitochondrial disease- Mitochondria in the cells are not producing enough energy. Different people are affected differently by it as the combinations of the mitochondria working and not working will differ.  Will affect body parts that require the highest amount of energy (have the highest mitochondria demand) like the kidney, liver, brain, heart and therefore can result in a lack of muscle coordination, poor growth, learning disabilities, organ failure.

Alstrom syndrome- Rare genetic condition that affects the main systems of the body, caused by mutations of a single gene which is automatically recessive. Mutated genes should be received from both parents to show symptoms, one gene from one parent shouldn’t affect a person. It is characterised in many ways including an Increase in loss of sight and hearing, heart disease, type 2 diabetes and short stature. There is no specific treatment.

Hyperinsulinemia- When someone has hyperinsulinemia they usually have more insulin in their blood compared to normal people. This results in people having a problem controlling their blood sugar, meaning that the pancreas is forced into secreting larger amounts of insulin to keep the blood sugar normal. With hyperinsulinemia people develop diabetes, weight gain, high triglyceride levels and atherosclerosis (this is when the arteries harden). It is caused by insulin resistance.

Multiple sclerosis- Neurological condition which targets the nerves in the body causing the nervous system to work abnormally. MS has a lot of different symptoms but no two people with MS will have the exact same set of symptoms. They include; fatigue, lack of muscle coordination, vision problems, bowel problem and vision problems. Treatments include physiotherapy, prescribed drugs and change in diet.

Steatosis- This is when a lot of different fat (lipids and triglycerides) accumulates in the liver which can lead to liver failure. Usually, the liver will repair itself when old liver cells are damaged however when there is constant damage to the liver e.g. if too much fat is built up permanent scarring takes place. There are two types of fatty liver; alcohol-related fatty liver and non-alcoholic fatty liver. It has no properly associated symptoms, however, it may result in experiencing liver inflammation, enlarged liver, weight loss and abdominal pain.

Leigh syndrome- Neurological disorder that affects babies during the first years of their life, causes children to die at an early age due to respiratory failure. Results in loss of moving abilities and intellectual abilities. There is a way around it, 3 people fertility technique in which the faulty gene is removed and is replaced with one from a healthy donor, however, this has a lot of ethical issues.

Fibromyalgia- Long term condition that amplifies painful sensations all over the body. It does this by altering the way your brain receives pain signals. People with fibromyalgia also feel fatigue, have memory issues and mood swing most of the time. It is thought to be caused by abnormal levels of chemicals in the brain and abnormal functioning of the nervous system which then can’t process pain messages carried in the body. Thought to be triggered by a stressful event.

References:

http://www.nhs.uk/conditions/synaesthesia/Pages/Introduction.aspx

https://rarediseases.org/rare-diseases/lysosomal-storage-disorders/

https://ghr.nlm.nih.gov/condition/alstrom-syndrome

https://en.wikipedia.org/wiki/Alstrom_syndrome

http://www.diabetes.co.uk/hyperinsulinemia.html

https://www.mssociety.org.uk/what-is-ms

http://denversdietdoctor.com/wp-content/uploads/2015/08/kraft-hyperinsulinemia-patterns.jpg https://patient.info/doctor/steatohepatitis-and-steatosis-fatty-liver

http://www.healthline.com/health/fatty-liver#causes3

https://ghr.nlm.nih.gov/condition/leigh-syndrome

http://www.nhs.uk/Conditions/Fibromyalgia/Pages/Introduction.aspx

 

By Sonia and Riya

Introductory blog

Hello,
We are a group of young year 12 students, interested in pursuing a career in the medical field. We have a passion for helping other people and thus why we are participating in this genome project, in attempt to help find a possible cure for a genetic disorder.
In the following blogs, we will be documenting our journey showing, the research we put into deciding what genetic disorder we should choose, why we will choose that specific disorder, and overall steps that will lead us to develop our genome to contradict the disorder. Our genome will be designed to improve the quality of life for people by acting as a cure and these blogs will portray our thought processes along the way.
By Sonia and Riya