Imperial are fighting these four rare diseases you may never have heard of

For Rare Disease Day 2018, Imperial researchers bring attention to four uncommon conditions, highlighting the importance of rare disease research.

The last day of February is marked as Rare Disease Day - an annual call to arms to raise awareness of the 7,000 known rare diseases. In Europe, a rare disease is defined as a disease or condition affecting fewer than five in 10,000 of the general population.  

The landscape of rare diseases is complex: most rare diseases are genetic (around 80%), some occur seemingly randomly, some are incurable, some have no known cause, and some have an incidence of one in a 1,000,000. Researchers in this field are faced with the challenge that rare diseases are less likely to receive funding and the awareness required to accelerate research.

Here are four rare diseases - some which you might be hearing about for the first time - that some of our academics are dedicated to researching, in the hope of uncovering improved treatment and cures.

1. Sarcoidosis

Sarcoidosis is an uncommon condition with an annual incidence of seven cases per 100,000 in the UK and no known cause. It is characterised by small patches of red and swollen tissue. Usually occurring in patients between 30-50 years of age, sarcoidosis commonly affects the lungs, lymph nodes, the eyes, the joints, and less commonly, the brain and the heart. It can also cause blood calcium levels to be raised and a big problem is the symptom of fatigue. The disease can be diagnosed by a chest X-ray, as well as by the stage of severity.

One of the challenges that face patients who have a rare disease is that sometimes diagnosis can be delayed because healthcare practitioners may be less familiar with the disease. The treatments for this disease often involve many different specialities given it is a multisystem disorder and so coordination of patient care is vital. Cardiac sarcoidosis is a good example of this and can be very serious, so timely diagnosis and expert treatment is essential.

Research in this area is so important to understand the underlying cause, the genetic influences on the disease, its presentation and course, but also research into how to diagnose sarcoidosis rapidly - ideally with a single blood test. This way, more patients would be identified and earlier. Whilst sarcoidosis is uncommon, when it does occur it can have a huge impact on a younger person's life and helping this group is a hugely rewarding area to work in as a specialist. 

I was motivated to become a specialist in a rare disease because there are many questions still to be answered and patients value seeing someone who has experience in treating the many faces of the disease. 

Dr Melissa Wickremasinghe is an Honorary Senior Lecturer at the National Heart and Lung Institute and Trust Lead for Interstitial Lung diseases and Sarcoidosis at Imperial College Healthcare NHS Trust.

2. Friedreich's ataxia

Friedreich's ataxia is an inherited disease that affects between one in 30,000 and one in 50,000 people in the UK. Patients normally present with clumsiness, lack of coordination and slurred speech in childhood - these symptoms gradually get worse until they are frequently confined to a wheelchair by early adulthood. Patients have an increased incidence of diabetes and often develop heart disease which leads to a reduced lifespan.

Friedreich's ataxia is currently incurable and, although rare with an incidence rate of one in 50,000 people, it affects a large number of people worldwide. At present, the main forms of therapy are supportive and do not affect the disease process itself. This is frustrating for both patient, carers and clinicians, as despite our efforts there is a relentless progression and the patients frequently become highly dependent on others.

However, recent research initiated in our lab has shown that the expansion of a DNA sequence (GAA) that causes the disease can close down a gene  - called Frataxin - and switch it off. By understanding how the Frataxin gene is closed down (resulting in the disease), we and others have shown that we can switch the Frataxin gene back on again using a vitamin called nicotinamide. Known as an 'epigenetic' modifier, nicotinamide targets the proteins that abnormally switch off the Frataxin gene.

This work was done in cells from patients, transgenic mice and more recently in patients. The results are promising in that we showed that we could switch on the Frataxin gene in a proof-of-concept study in patients. A further trial to test whether this treatment can halt the disease in its tracks, or even reverse some of the symptoms, is planned for the near future and will involve several centres across Europe.

Professor Richard Festenstein is a Clinical Professor of Molecular Medicine at the Department of Medicine.

3. Choriocarcinoma 

Choriocarcinoma is a rare and aggressive form of gestational trophoblastic disease (GTD) - a cancer brought on during or after pregnancy. It can develop several years after pregnancy and often after a molar pregnancy - where abnormal cells grow in the womb instead of a healthy foetus. Globally, 18,000 women are diagnosed every year with cancerous forms of GTD. Most of these women are cured with chemotherapy or surgery but up to five per cent die having not responded to treatment.

I was recently involved in a clinical trial to test whether an immunotherapy drug called pembrolizumab - used successfully to treat lung cancer - could be used to cure GTD in women who did not respond to conventional treatments like chemotherapy and surgery.

The results of our early-stage study, published in the Lancet, have confirmed our hypothesis and it has widespread implications on how we treat this disease in the UK and around the world. This treatment may well take us very close to our target of 100 per cent cure rate. We have only treated a small number of patients so far with pembrolizumab, but NHS England has agreed on provisional funding to treat more cases of cancerous GTD with it for the next two years at Charing Cross and Weston Park Hospital (Sheffield) - the only two hospitals in the country that treat the condition.

We will carry out further studies to see whether pembrolizumab impacts subsequent fertility. This is important as many of our patients want to have children after they are cured of GTD. If we find that pembrolizumab does not affect fertility then it is possible this therapy could be used to treat all high-risk cases of GTD.

Michael Seckl is Professor of Molecular Cancer Medicine at the Department of Surgery and Cancer

This was originally published in Pulse Magazine and is republished here with permission from Imperial College Healthcare NHS Trust.

4. Herpes simplex encephalitis

In a nutshell, encephalitis refers to the inflammation of the brain. Up until recently it was thought that encephalitis was simply either a viral or bacterial infection. However, in 2005 research described a new version of the disease: auto-immune or 'anti-NMDAR encephalitis', which is caused by antibodies that attack the brain tissue. In all its forms, encephalitis is incredibly rare: herpes simplex encephalitis (HSE), for instance, affects approximately one in 1,000,000 children. Although there are clear treatment routes available, viral encephalitis is incredibly destructive. The virus can cause irreversible damage in the brain, which will continue to impact upon a patient's quality of life well after their short-term recovery from the disease itself. 

One of the key aims of my research is to understand the risk factors associated with encephalitis in all its forms: why is that one person should be predisposed to developing this life-threatening disease, and 999,999 others not? Does the reason exist in our genes? This is a particularly important question to ask in the context of looking at the relationship between these different forms of the disease.

We know that there are people who have been diagnosed with anti-NMDAR encephalitis who previously had HSE.  If this is the case that suffering from HSE might mean it's more likely that you'll develop anti-NMDAR, then at the very least this offers us another point of intervention. If we know this particular subset of patients are at-risk, we can try and halt the progression of the disease, or at a minimum catch what is happening within the body, as it happens.

There is plenty of work left to do in raising the profile of the disease, but awareness incentives have the potential to help us answer some of the pressing questions. By raising awareness, people suffering from encephalitis - and their family and friends - will have more of an inclination to learn about the disease and help with ongoing research. 

Dr Vanessa Sancho-Shimizu is a Senior Research Fellow in the Division of Infectious Diseases, Department of Medicine.