News articles in recent weeks have talked about repurposed drugs being used to treat COVID-19 patients including drugs used for MS. We explore why existing MS drugs might be used for COVID-19.

white blood cells

There are currently around 150 drugs being trialled in different countries, aiming to establish if they are effective against the novel coronavirus (COVID-19).  Most are repurposed drugs, that is, they are existing drugs used to treat other conditions such as malaria, ebola and multiple sclerosis, now being tested in patients with COVID-19.

Why re-purpose drugs?

Novel drug development is slow and impractical, particularly in a pandemic.  An alternative approach is to repurpose existing drugs - these drugs will already have proven themselves to be safe in early testing, meaning they can be fast-tracked straight into the final stages of clinical development.  There are other benefits in terms of cost, particularly if the drug is off-patent, and ease of production if the drug is already on the market.

Examples of this happening with MS drugs include ibudilast (an asthma drug), metformin (a diabetes drug)  and cancer drugs such as cladribine an mitoxantrone.

There are currently three categories of drugs being investigated to treat COVID-19:

  1. Antiviral drugs, targeting the coronavirus and its ability to survive and replicate inside the body
  2. Antibodies that target the virus; taken from survivors' blood or made in a lab
  3. Drugs that calm the immune system (severe Covid-19 is thought to be caused by patients' immune systems over-reacting and damaging the body) – these are the ones similar to MS drugs

Inflammatory response

A simple inflammatory response — the innate immune system — is your body's first line of defence. Your immune system is a network of organs, cells and tissues.  Infection-fighting white blood cells (leukocytes) find and destroy substances and micro-organisms that the body recognises as a threat.

MS is considered to be an auto-immune disorder, where the body’s immune system mistakenly considers itself to be a threat and mounts an inflammatory attack against the target tissue (in this case the myelin sheath surrounding many nerve cells).

COVID-19 also illicits an inflammatory response – the virus persisting in the body can cause significant damage to the lungs and blood vessels and may lead to inflammatory over-reaction in the most severe cases. As mentioned above, aa part of a healthy immune response, white blood cells recognise the virus. They release chemicals called cytokines that attract other immune cells to the site of an infection. These are activated so that they can kill cells infected with the virus. But if too many cytokines are released in a short period, cells not infected by virus may also be killed – causing damage to healthy tissue. In patients with severe COVID-19, cytokine levels are far higher than in patients with mild disease.

Steroids (dexamethasone)

The use of dexamethasone, a steroid, has been a significant breakthrough in the fight against coronavirus.

The UK's Recovery trial showed dexamethasone cut the risk of death by a third for patients on ventilators and by a fifth for those on oxygen. 2,104 patients received this drug by mouth or injection and were compared to 4,321 who received standard care alone.

Dexamethasone is a steroid that dampens down the inflammatory response in the body. It does this by preventing infection-fighting white blood cells from travelling to the area of damage in your body. (This is why you are more prone to infection while taking steroids). It is commonly used for eye inflammation and to decrease swelling associated with tumours in the spine. It is also used in  some autoimmune diseases.

Crucially it is also low cost, meaning that it could be used widely around the world. However, the drug does not appear to have any benefit in people with milder symptoms. Steroid therapy dampens the immune response in general, and is rather a crude instrument, attempting to fine-tune a very complex machine (the immune system).  Newer treatments are emerging that can target and block specific cytokines involved in these harmful responses.

Steroids like these are used to treat acute MS symptoms – dexamethasone was  originally approved by the U.S. Food and Drug Administration in 1958 for the treatment of acute relapses in MS. It is believed that it works by an anti-inflammatory mechanism and it works as an immunosuppressor.

Interferon beta

Interferon beta is an MS DMT being repurposed for COVID 19 patients. Interferon beta is a protein that the body normally makes to dampen down inflammation (broadly known as a cytokine).

The UK company Synairgen is delivering the drug directly to Covid-19 patients' lungs using a nebuliser. Interferon beta was one of the first DMTs for MS, available since the mid-1990s and delivered by injection (unlike nebulisers, as used in the study above).

Initial findings suggest that the treatment significantly reduced the odds of a patient in hospital developing severe disease, but larger clinical trials are now needed.  The double-blind trial involved 101 volunteers who had been admitted for treatment at nine UK hospitals for Covid-19 infections. There was also research in 2004 into interferon beta and SARS (another novel coronavirus).

According to the study, the risk of developing severe COVID-19 symptoms that required ventilation or caused death during the treatment period of 16 days was reduced by 79 percent for patients in the interferon group, compared to those who received placebo.

The company also reported that patients who received this drug were more than twice as likely to recover within the course of the treatment period compared to those receiving placebo. The measure of breathlessness was also “markedly reduced”.

Interestingly, the UK Recovery trial is now recruiting a trial for Low-dose Dexamethasone, another steroid which has also been used to treat MS, so watch this space.

What does this mean?

Both the drugs mentioned are connected to the inflammatory response and the immune system,  felt to be responsible for causing the damage of severe COVID-19 and in MS. From a scientific perspective, it is interesting and exciting to see the speed at which some of this research is progressing, with such impressive results. However this does not mean that any particular MS drug will be beneficial in treating COVID-19, and it’s important to remember these drugs do not stop you contracting COVID-19, rather it is for treating people who are severely unwell with the virus.

MS & COVID-19

COVID-19 infection is more likely to occur, and more likely to have serious consequences, in people with compromised immune systems. All MS disease-modifying therapies affect the immune system, to varying degrees.  Interferon beta 1a and 1b do not significantly increase the risk of systemic viral infections.

Research into MS and COVID-19 is ongoing.  More research is needed into whether people with MS are more vulnerable to contracting the virus, but it is not currently felt that MS alone increases your risk of developing COVID-19 or a more severe course of the disease .  This is felt to be influenced by whether you are taking steroids or DMTs which may be immunosuppressive and how the body reacts to COVID-19 if you are living with more advanced forms of MS.

Please consider joining a study gathering data so we can find out more https://platform.qmenta.com/covid19_ms_patient

Other anti-inflammatory strategies

As you will know from the Overcoming MS program, vitamin D plays an important role in modulating the immune and inflammation system so there have been discussions about vitamin D and it’s effect on preventing or treating COVID-19.  At present, there is some evidence to suggest that lower levels of vitamin D are associated with a more severe course of COVID-19, but further research is needed.  In the meantime, there is absolutely no reason to stop taking your OMS recommended vitamin D doses; it may very well prove to be even more important in the coming months, both for us and our friends and families.

Reviewed by Medical Advisor Dr Jonathan White


References:

  1. https://pharma.nridigital.com/pharma_jun20/repurposing_drugs_covid-19
  2. http://chemocare.com/chemotherapy/drug-info/dexamethasone.aspx
  3. https://multiplesclerosisnewstoday.com/decadron-dexamethasone
  4. https://www.recoverytrial.net/news/low-cost-dexamethasone-reduces-death-by-up-to-one-third-in-hospitalised-patients-with-severe-respiratory-complications-of-covid-19
  5. https://www.synairgen.com/wp-content/uploads/2020/07/200720-Synairgen-announces-positive-results-from-trial-of-SNG001-in-hospitalised-COVID-19-patients.pdf
  6. https://coronavirusexplained.ukri.org/en/article/cad0012/
COVID-19
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