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  • Yasemin Cole

Reimagining Approaches to Healthcare Amidst a Rare Disease Crisis

One of the many things the Covid-19 pandemic taught us is that chaos and uncertainty will ensue if emergency structural systems are not in place in advance. Three years after Covid-19 began spreading worldwide, we still grapple with its aftershocks in medicine. In the UK, the NHS has seen the most dramatic effects, as an already overburdened system was forced to shift priorities from chronic and preventative care to infectious disease response and back again. Research has shown that cancer care has not kept pace in these three years. A study by Cancer Research UK illuminated these staggering effects: the overall number of individuals participating in cancer screening tests decreased by 15% from 2019 to 2021. Individuals seen by a specialist within 14 days decreased from higher than 93% (prior to May 2020) to 78.8%. The healthcare crisis persists to this day and will likely worsen due to cuts to healthcare and research funding as the UK continues to reimagine life after Brexit.

In the realm of rare diseases, there is a pressing need to innovate diagnostic and prognostic tests, given the already long wait times and delays in care. Despite being considered uncommon, rare diseases are estimated to afflict around 10% of the population, which is the same prevalence as asthma or diabetes in the US. In total, this equates to a sizeable percentage of patients who require specialised care. Patients with rare diseases and cancers have felt this strain acutely, as delays in their clinical care have exacerbated their own personal crises. What if diagnosis and prognosis for rare diseases and cancers could be quick, allowing more time for treatment? What if, for instance, there was a simple cancer test similar to the routine blood tests that already exist for glucose or cholesterol levels? And, moreover, what if this test was low-cost, had high sensitivity/specificity, and could translate quickly from the lab into the clinic? That’s the type of technology my lab and I are working on. Historically, this type of diagnostic test has been used for blood cancer, but in the past decade scientists have aimed to apply this approach to other cancers.

"Despite being considered uncommon, rare diseases are estimated to afflict around 10% of the population, which is the same prevalence of asthma or diabetes in the US. In total, this equates to a sizeable percentage of patients who require specialised care."

One such type of rare disease is pheochromocytoma and paraganglioma (PPGL) syndrome, in which patients with a single inherited genetic mutation may develop cancers throughout their bodies. When these cancers may develop is unknown. Unfortunately, we also do not have sensitive clinical markers to know whether this kind of tumour will be benign or malignant. We often learn that an individual has cancer after they report insidious symptoms, like panic attacks, high blood pressure, or palpitations. In some cases we learn of the tumours too late and the disease may no longer be curable. My lab is aiming to produce a test that could detect whether cancer is likely to metastasise before patients have symptoms.

During my PhD under the supervision of Dr Ruth Casey and Professor Eamonn Maher, I am collecting plasma samples from patients at Addenbrooke’s Hospital who have PPGL syndrome. Patients may be undergoing treatment for a tumour, have had a past tumour, or are undergoing asymptomatic surveillance because they harbour a genetic variant that predisposes them to PPGL development over their lifetime. By prospectively collecting blood samples, we hope to identify tumour- and/or gene-specific molecules that can be tracked over time during a patient's clinical course. This patient population is unique because their cellular metabolism (e.g. breaking down glucose in cells) is impacted. Therefore, we predict that we can detect abnormal substances (i.e. metabolites) in the blood that are associated with the genetic mutation. This could lead to early diagnosis and treatment.

A diagram showing PPGL patients being sampled at various points before, during, and after genetic diagnosis, surgery, radiotherapy, and cancer diagnosis. The bottom panel of the figure is a schematic showing blood samples separated into plasma and RBCs, followed by analysis in a liquid chromatography/mass spectroscopy machine which displays a graph of "Intensity" against "m/z".
The top panel illustrates patients recruited into the blood study and when blood samples are collected (red boxes). The lower panel indicates how blood samples are analysed in the laboratory: starting with a sample from a patient, followed by blood processing to extract the acellular component of the blood (called plasma), and finally metabolite identity and discovery on a liquid chromatography/mass spectroscopy machine. Photo credit: Yasemin Cole.

Given the current demands on the NHS healthcare system, patients with rare diseases bear the largest burden. Their diagnoses require consistent speciality care and clinical surveillance. Over the past few years, rare disease patients have experienced long wait times for critical tests, including genetic sequencing and annual imaging. We hope our blood test may help identify patients whose tumours are recurring or progressing, enabling triage of patients needing focused clinical attention.

Confronting an infectious disease pandemic over the last three years has reinforced that prevention and detection are paramount in medicine. The NHS is increasingly stretched as funding is restricted and clinical demands increase. Services for patients with rare cancers are especially struggling, as the management of these chronic conditions is dependent on a fully functional medical system. My colleagues and I imagine a future where we can turn a simple blood test into a precision diagnostics tool for patients with PPGL syndromes and individuals with other rare diseases. While further research and larger sample sizes are imperative to fully implement these results and roll out clinical-grade tests, we are hopeful that we can help tackle the rare disease crisis in medicine.


Yasemin Cole [2020] is a PhD student studying hereditary cancer syndromes and genomics in the Department of Medical Genetics.

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