This week’s blog was written by Remarez Sheehan, a 4th year medical student from the University of Oxford. Remarez entered The 2020 Student Voice Prize and was shortlisted for the brilliant essay “Seeking similarities in difference: How COVID-19 has highlighted the dual importance of individual experience and unifying commonality in rare disease research.”
Read Remarez’s essay below and be sure to enter The 2021 Student Voice Prize when it returns this Autumn!
Hello, my name is Remi and I’m currently a 4th year medical student at the University of Oxford. I’m quite extroverted and love speaking with different types of people, which is what drew me to medicine in the first place.
Indeed, one of the main aspects of The Student Voice Prize I enjoyed was getting to know AL and learning about the unique difficulties faced by those with rare diseases. As a medical student looking from the outside, there is always a ceiling to our understanding regarding the actual experience of a disease – especially rare ones – and it is because of people like AL, who share their personal stories and invite us into their lives, that we can hope to become empathetic and patient-centred clinicians.
A key lesson I have taken away from the experience is that those with rare diseases are so much more than case reports or interesting footnotes in a textbook, and instead represent some of the most resilient and kind members of society. It is our responsibility as healthcare workers to ensure all patients feel heard and respected, and the work of Findacure and Medics for Rare Diseases is a great step towards that.
Seeking similarities in difference: How COVID-19 has highlighted the dual importance of individual experience and unifying commonality in rare disease research.
The COVID-19 pandemic has had a far-reaching impact across all aspects of life, quite literally changing the way we interact and perhaps even the way we think. That said, not all areas have been impacted to the same degree, with some groups and sectors simply lacking the logistical reserve to maintain normal operations in the context of a pandemic.
Rare disease research (RDR) is a prime example; except here the impact of the pandemic is exacerbated by the unsatisfactory level of ‘normal’ operations that have long preceded COVID-19. To elaborate, raising awareness and funds for rare diseases has always been an issue, and where research has taken place clinical translatability has often been limited. Altogether, this has significantly strained RDR and highlighted weaknesses that we, as current or future clinicians, must address if we are to improve the lives and wellbeing of those living with rare disease.
With the help and insight afforded to me by a discussion with AL, who lives with a rare condition called Hereditary Spastic Paraplegia (HSP), I will outline how COVID-19 has impacted RDR and, more productively, will suggest how its robustness may be improved. At the same time, I hope to raise awareness for HSP and become more empathetic to the health inequality faced by those with rare diseases.
What is HSP?
HSP encompasses a heterogenous group of neurodegenerative disorders characterised by progressive spasticity and subsequent paralysis of the lower limbs. It’s important to recognise that, aside from this hallmark feature, there are a wide variety of symptoms someone with HSP may experience. For example, AL described incontinence, pain, fatigue and depression. In essence, no two individuals with HSP will necessarily have the same experience.
A large part of this variation may be explained by the over 80 subtypes of HSP that have been described thus far, based on the presence of different spastic paraplegia gene (SPG) variants. This may also account for the lack of progress made in developing therapies capable of pausing, reversing or preventing the neurodegeneration and preserving mobility. Instead, those with HSP are offered any of a long-list of non-HSP-specific treatments for symptoms, such as muscle relaxants like baclofen and physiotherapy.
How has COVID-19 impacted RDR?
The impact of COVID-19 on RDR can be thought in terms of i) researcher and lab availability, ii) participant engagement and iii) fundraising and awareness:
Perhaps the most apparent and immediate consequence of COVID-19 on RDR in the UK (and elsewhere) was the forced closure of labs and pausing of their operations during lockdown. Most significantly, this has stalled countless clinical trials aiming to determine the safety and effectiveness of therapies for rare diseases– many of which will not have effective existing therapies. Sadly, this will delay successful therapies reaching those in need and- in the worse cases- may lead to fatalities where individuals can no longer access life-saving experimental treatment as part of a clinical trial. Even where research is allowed to restart, it is likely that academic clinicians will need to spend more of their time doing routine clinic rather than RDR. Accompanying reduced research hours, a shortage of participants may arise following the requirement of clinical sites to pause trial recruitment.
Although top-down outreach from drug companies and research bodies tends to be the main method of recruitment for more common diseases, I would argue that it is bottom-up engagement from those with rare diseases that drives research within this domain. In part, this is due to a scarcity of available data and eligible participants, which make recruitment drives less effective because the target is less clear. Given this, it is important to consider how COVID-19 may have affected participant engagement and recruitment in RDR from the perspective of potential participants.
I would argue that a key determinant of an individual’s decision to partake in research depends on their involvement with local/national representative organisations (e.g. HSP support group (HSPSG)3). Among other things, these organisations provide information about existing and ongoing research and act as a platform for informed and willing participants to get involved with relevant research projects and trials. How, then, has COVID-19 changed engagement with representative groups?
On one hand, the implementation of lockdown and social distancing measures places a barrier on physical face-to-face events and meetings. Paradoxically, this may have actually widened participation within rare disease groups because of the remote nature of electronic meetings, which overcome geographical and mobility barriers, and can increase connectivity among members. This consideration would be particularly relevant for rare diseases characterised by immobility, like HSP. Indeed, AL informed me that there has been increasing attendance in the HSPSG e-meetings since the start of lockdown and, excitingly, the group had even hosted their annual general meeting online.
Ultimately, COVID-19’s overall effect on group participation and research engagement in this period will depend on how many are willing to embrace technology and partake in meetings from their homes. Where accessibility isn’t an issue, it is also important to consider the effect of COVID-19 on global mental health and social motivation. Those with rare disease have been particularly affected by COVID-19, with one survey in Hong Kong finding that 79% of 272 people with rare diseases felt that their mental health had been negatively impacted2. Certainly, this could negatively influence engagement in RDR.
COVID-19 has placed a disproportionately large strain on RDR due to its reliance on public awareness and charity for funding, rather than having a more reliable income stream from larger funding bodies. For the greater part of a year national and international attention has been consumed by COVID-19, subsequently bumping other medical issues (e.g. cancer treatments) down the list of priorities which, I’m afraid to say, has left rare diseases like HSP at the bottom of the pile. The human impact of this is exemplified by the Pirovolakis family in Canada, whose fundraising effort to afford experimental gene therapy for a rare HSP variant (SPG50) their son carries has been stalled by COVID-19, particularly heart-breaking given the time-dependent and progressive nature of SPG504. A central concern here is that research will not be able to restart even if the labs are open because of inadequate funds.
What lessons can be learned?
COVID-19 has made it clear that RDR is not adequately resilient to external disruption, and suggests a change of approach may be necessary. Talking to AL about their thoughts on HSP research, an important point that came up was the feeling that sometimes the research may be too narrow in its approach, inadequately attending to the wider wellbeing and narrative of those to which it pertains. Put simply: how can we aim to treat a population we do not understand?
A likely solution to this problem would be to increase the use of natural histories and quality of life assessments in RDR.
Natural histories reflect a person’s long-term experience of their rare disease, including the progression and evolution of their symptoms. Incorporating natural histories should align research aims with population needs, central to which is the best quality of life possible. Natural histories also increase the availability of data by including historical (living or deceased) controls in active clinical trials5. Encouragingly, the implementation of natural history registries seems to be on the rise: in particular, the SPATAX network launched two international registries for SPG11 and SPG15 earlier this year6. Aside from the benefits to research, a major benefit of these registries is the voice it gives to those with rare diseases, along with the opportunity to share and compare their experiences with each other.
Elsewhere, a narrow research framework focuses too much on the differences within and between rare diseases. While rare diseases are rare, phenotypes across domain-related disorders (e.g. those involving neurodegeneration) may be more common. Thus, by looking for similarities we might hope to optimise research efficiency; pooling resources and mindpower into a common problem with the end-goal of a therapy applicable to a larger group. The potential of this type of approach is well demonstrated by the Crosby group in Exeter, whose lateral thinking allowed them to use a finding in a relatively rare HSP subtype, SPG5, to inform and target experiments in related subtypes and conditions. Essentially, their
characterisation of the SPG5 mutation led them to the breakthrough that a disturbance to fat processing is a common signature of motoneuron disorders7. This discovery is likely to influence testing and focus interventions across all of these disorders, thereby maximising clinical translatability.
To summarise, the impact of COVID-19 has been to slow and delay RDR because in captivating global attention, rare diseases and their importance have fallen out of people’s minds. While COVID-19 will eventually settle (touch wood!), its lessons should not be overlooked: RDR needs to utilise a broader, more personable approach, which attends to individual narratives and commonalities between them. As for ourselves, we should all do more to raise the banner of rare diseases, offering support to organisations like HSPSG in whatever ways (big or small) that we can.