This week has been an interesting week. Donald Trump’s behaviour in the final throws of his term has been that of a desperate man. However, for some political leaders such as Kin Jong-un of North Korea, his actions might be re-affirming.
It feels as if the net is closing in on Donald Trump and there are growing calls for his resignation. Even his Twitter account has been removed in the fear that he may use the platform to further incite his 89 million followers. However, apparently there have been reports of him trying to open a new account under an assumed alias.
Meanwhile in December 2020 the rest of humanity passed an unusual milestone. We have reached a cross-over point where the sum of all our activities, which means our production of materials such as concrete, metal, glass, bricks and tarmac, is now greater than the entire mass (or biomass) of all living things put together. This is a truly remarkable fact.
This is according to research published in the weekly scientific journal ‘Nature’ in a study by researchers from the Weizmann Institute of Science in Israel. Even the amount of plastic we generate is larger in mass than all land and marine mammals. The researchers said they wanted to provide an objective and rigorous measure of the reality of the balance between man and nature.
On an even more obscure level and equally surprising it was also estimated last year the number of digital bits (as in computing) will overtake the number of atoms on Earth within 150 years. By 2170, according to research from Portsmouth University, the world will be ‘mostly computer simulated and dominated by digital bits and computer code’. The study estimated that there will be 133 quindecillion (133 followed by 48 zeroes) bits in existence – the same as the estimated number of atoms on the planet. How strange is that!
But research and science have brought new hope to what is currently a rather bleak landscape. Any good news is refreshing, and this does not just include the arthritis drug tocilizumab (the one that Boris couldn’t pronounce) that has been re-purposed to treat COVID-19. There have been positive scientific breakthroughs that provide new hope for millions of people living with multiple sclerosis. MS is a chronic condition that affects an estimated 2.5 million people worldwide.
The Uncertain Epidemiology of Multiple Sclerosis
It is important to remember that the pandemic has had a serious knock-on effect on funding for future medical research, with the cancellation of major fundraising events such as the London Marathon. The MS Society is set to lose some 30% of its income this year – around £10m – which means research both now and in the future will be affected. Any good news surrounding this condition is therefore especially welcome.
The epidemiology regarding MS is still surprisingly unclear. Latest research suggests that the proportion of women with Multiple Sclerosis is increasing and that roughly between two and three women have MS for every man with the condition. There are incongruities in the geographical distribution of MS. In general, the prevalence of MS increases as you travel further north or south from the equator. Those parts of Asia, Africa and America continents that lie on the equator have exceptionally low levels of MS, whilst countries at higher latitudes such as Canada and Scotland have particularly high rates. People living beyond the 40o latitude north or south of the equator are therefore far more likely to develop MS.
Geographical spread does not however tell the whole story as further studies also demonstrate that some ethnic groups have a much lower prevalence of MS, even though they might live in a country where MS is common. This is illustrated by the fact that ethnic groups such as Sami (roughly 80,000 people) of northern Scandinavia and the Inuits in Canada (65,000 people) have exceptionally low rates of MS. A similar pattern is observed amongst the Maoris of New Zealand.
What is Multiple Sclerosis?
So, what happens in MS? Most of us have at least some idea but Multiple Sclerosis quite literally means ‘many scars’ and this of course refers to the lesions which manifest in the central nervous system. The lesions are comprised mainly of dead nerve cells whose projections called axons have been stripped of their rich fatty protective covering ( a myelin sheath) that allows conduction of electrical nerve impulses. The body it would seem for reasons that remain a mystery makes a mistake and recognises the myelin for a more harmful substance and attacks it leading to lesion formation. The lack of electrical nerve impulses prevents signals from reaching their target organs or structures such as eyes or muscles or other body parts.
In the early stages, MS causes eye problems such as temporary loss of vision, difficulties with balance, dizziness, muscle spasms and tremors. In the longer term, nerves that have been stripped of their myelin degenerate, and it is the loss of these that leads to disability. MS is essentially a chronic disease that typically begins in early adulthood. Most people live with their condition throughout their lives although it may serve to reduce life expectancy by 10-15 years.
New Research Surrounding MS
It was previously thought that it was impossible to regenerate myelin, but a new body of research funded by the Multiple Sclerosis Society and undertaken by Cambridge University in 2020 in a Phase 2 trial demonstrated that, at least in theory, remyelination is possible. The study used brain scans to survey changes in patients who were in the early stages of the condition who were given a drug called bexarotene. Unfortunately the drug caused some potentially dangerous side effects (inflammation of the pancreas and raised blood lipid levels) but scans revealed that neurons regrew their myelin sheaths.
This clinical trial proved regeneration of the myelin sheath is possible. Sadly, the side effects of bexarotene are too severe making it inappropriate for submission into a Phase 3 trial. It has however given researchers a renewed momentum and new investigations using metformin (a common inexpensive diabetes medication) and clemastin (an antihistamine) are planned. It was demonstrated in 2019 that the combination of these two medications could stimulate remyelination using animal-based models. These results were published in the peer-reviewed scientific journal ‘Cell Stem Cell’.
Other investigations have also revealed that a combination of fasting and metformin can rejuvenate stem cells in the brain called oligodendrocytes (this was performed using animal-based models). These stem cells go on to develop into myelin-producing cells that remyelinate damaged nerves.
There is also encouraging news from other recent investigations. Trials are currently underway to assess if simvastatin, the cholesterol lowering drug, can slow progression of Multiple Sclerosis. It will involve 1,050 people with secondary progressive MS. It began in March 2017 and will take six years to complete. Another study published in the open access journal JCI Insight from Oregon Health & Science University in 2019 developed a synthetic compound sobetirome.
The researchers developed a derivative of sobetirome (Sob-AM2) that penetrates the blood brain barrier allowing access to the brain, enabling a tenfold increase in infiltration of the substance to the central nervous system. Sobetirome was developed as a synthetic molecule more than two decades ago, initially with an eye toward using it to lower cholesterol, but it has been repurposed and trialled for MS. Researchers have found that the treatment in mice not only triggered myelin repair, but they also measured substantial motor improvements.
MS affects 1 in 600 people in the UK, where about 100,000 people live with the condition so any progress is welcome. Susan Kohlhaas, the director of research at the Multiple Sclerosis Society, has been involved in the funding at Cambridge University. She comments: “We can see a future where nobody needs to worry about MS getting worse, or eventually needing a wheelchair, but for this to happen we need treatments that repair myelin. This research demonstrates myelin repair therapies are within our grasp, and we’re closer than ever to finding treatments for everyone living with MS.”