What Happens When Great Scientists Get Diagnosed With Rare Diseases?

by Doug Wylie

In December 2015 after spending two months at St George’s Neurology Department and undergoing numerous blood tests, MRIs, PET and CT scans, three lumbar punctures and finally a brain biopsy operation– I was eventually diagnosed with an even rarer form of an already rare disease called isolated neuro sarcoidosis. No, I hadn’t heard of it either!

Previously I was a very healthy and active 37-year-old male having played rugby most of my life and recently took up rowing at Imperial College London where I was finishing up my research PhD on novel single cell biology micro delivery technologies using lasers and microfluidics (more about that later!)

Despite being in the best shape of my life and having kept up with guys half my age in the rowing club, I started to get ill. It happened gradually at first, what felt like a stomach bug and the odd very mild wobble while running or walking. However within about two months I was basically in bed 20 hours a day, suffering from nausea, headaches, double vision, shaking in my right leg and more severe balance problems and dizziness.

Once in hospital things got worse and it soon became obvious that I had something very unusual with the MRIs showing lesions in my cerebellum and brainstem. Although the nausea eventually went away my eyes started having a condition called nystagmus where the pupils oscillate back and forth uncontrollably. Imagine shaking your head back and forth for about 10 months, whilst at the same time having double vision dizziness and severe ataxia and shaking not to mention being in a wheelchair for anything more than ten metres! Recently my speech has also become impaired due to the inflammation in my cerebellum spreading to the neurons that control the nerves to the muscles around my mouth. But, somewhat ironically, even though I talk slower I can still use speech to text software to write this page as my usually fast (and sometimes hard to understand Northern Irish accent) seemingly has become easier for the software to decipher!

This disease has left me both severely physically and sensorally disabled much more than even I thought imaginable however the mind is still strong, at least for now! I am still a scientist first and foremost and luckily have had more than 15 years experience in both academia and industry across multiple disciplines from physics and experimental biophysics to working as a molecular and cellular biologist in America to surface chemistry, laser-based optical microscopy and microfluidics as part of my research PhD at Imperial College in London.

This unusual but extremely useful background has allowed me direct and indirect access to cutting age research techniques and methodologies not to mention some very smart and well-connected people! Having this unique combination can be applied directly to neuro sarcoidosis research. The science and technology already exists to both find the cause and develop a cure for this and other related sarcoidosis diseases. We just need to focus our energies and better fund both research and public awareness towards this lesser-known but often debilitating disease. This is where the potentially game changing combination of you and BRAINNS come into play.

Sarcoidosis itself is a rare disease of unknown origin and has no cure. It can affect any organ, most commonly in the lungs and in even rarer cases the brain and central nervous system. It is thought to be an auto inflammatory/autoimmune disease and is diagnosed by the identification of what is called non-necrotising granulomatous inflammation in a tissue biopsy sample. These small grain like granulomas can be seen under the microscope and are basically immune cells forming a protective or destructive (depending on how you look at it) casing around a mixture of healthy cells and perhaps cells containing an unknown infectious trigger such as mycobacteria. Because healthy tissue gets destroyed in the granulomas which also cause inflammation in the surrounding tissue it is classed as an auto immune disease. If we can find (and we will as long as we look hard enough) the cause(s) through our various techniques such as immunohistochemistry, mass spectrometry, next generation sequencing and microscopy then better tailored treatment and a cure(s) will be much easier and quicker to develop. Instead of 10 to 15 years we are looking at potentially 3 to 5. As I have already said the science and technology exists right now we just have to pull our resources and make use of it.

On this note my consultant neurologist at the Royal free Dr Desmond Kidd is one of the few neuro sarcoidosis experts in the UK. He has managed to gather one of the largest patient sample groups with over 200 neuro sarcoidosis and about 25 isolated neuro sarcoidosis, with around 35 actual brain biopsy tissue samples (25 isolated and 10 general neuro sarcoidosis). He is starting his recently approved research and has generously allowed me access to the 35 brain tissue samples. Through his connections at the Royal free and UCL and my connections at Imperial we potentially have both the expertise and facilities already available to do the cutting age research necessary. The goal is to get more official government funding in terms of approved research proposals as well as public funding for additional or preliminary testing on a few samples to optimise the various protocols and methods needed. Money will of course also go to raising public awareness through social media, newspaper adverts and journalist pieces etc.

I also have potentially a very cool idea regarding using modern image analysis software on more powerful recently developed 7 Tesla MRI machines in order to make a more reliable and confident clinical diagnosis of neuro and especially isolated neuro sarcoidosis. Current 3 Tesla MRIs cannot resolve the subtle differences between inflammation related to for example multiple sclerosis versus neuro sarcoidosis patients. Indeed neuro sarcoidosis is often called the great mimicker. Often an invasive and expensive brain biopsy is required to prove the presence of the granulomas. If this can be more accurately and reliably proven by newer MRI and imaging software then a diagnosis can be given much quicker and more confidently saving both the patient the worry of having to go through a brain operation and saving the NHS hundreds of thousands if not millions of pounds a year on unnecessary brain biopsies and longer pre-diagnosis bed occupation times. An initial investigative study into 7T MRIs of MS versus NS patients will be relatively easy and quick to set up and run and is the sort of research where your donations toward BRAINNS will have the most impact.

This disease affects everyone differently depending on where exactly the granulomas are. Unfortunately in my case the granulomas are localised mainly in my cerebellum and have already caused permanent damage and significant loss of neurons, hence the extremely debilitating symptoms despite the relatively small volume of damage. The cerebellum is densely packed with different types of neurons and has the same amount of cells as the rest of the brain but only a 10^th of the volume. Basically every cell counts. A good analogy would be that of a supercar having dirty or missing spark plugs in its engine. Everything else is fine but because of the missing and dirty spark plugs the car barely sputters along no matter what you do. The only way is to clean and replace the spark plugs. This is of course much easier to do in a car than the human brain but as I keep saying the science and technology already exist.

If I was physically able to go in the lab I would do the research myself. Research is what I do, or at least did, for a living and I loved it and was pretty good at it J. Unfortunately this is no longer possible but the mind is still strong and as long as I can communicate my ideas to the right people and use my laptop effectively I believe that I can still play a big part in finding a cause and developing a cure and hence better treatment options for this difficult disease.

A lot of this research and future findings could be applied to other autoimmune and neurological conditions as a lot of autoimmune disorders are similar in pathological and biological terms. It’s just that different organs and tissues are affected hence the multitude of different names for the diseases but the underlying mechanisms are often very similar.

With your help I believe we can greatly speed up the process of discovery and towards developing a cure.

2016 has most certainly been an annus horribilis and there were some dark times were I didn’t think I was physically capable of carrying on. Thankfully I am not alone and have the most amazing wife, family, friends and colleagues who have been there to share and lighten the burden. I couldn’t do this without them and especially my wonderful wife Gail. I honestly do not know what I would do without her. She is and will always be my rock. I have leaned on her shoulders far more often than a husband should and hopefully one day in the not too distant future she can lean on mine again, only this time without me falling over!

Despite having a severe physical disability as long as the mind is strong and you have the right support network it is surprising what can still be achieved.

Learn. Share. Give: https://www.justgiving.com/crowdfunding/douglas-wylie