Research Grants

Dr Diane Ritchie ‘Investigating the presence and replication potential of prion protein aggregates in preparations of human pituitary-derived growth hormone (hGH) that are implicated in UK cases of iatrogenic CJD’

Creutzfeldt-Jakob disease (CJD) is a fatal brain disease caused by an abnormal and infectious form of the prion protein (also known as prions), which replicates and forms aggregates in the brain. CJD most commonly occurs in individuals sporadically. However, some forms of CJD are inherited, and others can be acquired via transmission from other humans, or in some cases from animals. Iatrogenic CJD (iCJD) is caused by the accidental patient-to-patient spread of infectious prions through specific medical or surgical treatments.  The commonest cause of iCJD in the UK is treatment with cadaveric human pituitary-derived growth hormone (hGH) which had become contaminated with prions, presumably from deceased individuals with CJD.  In 1985, the first case of iCJD in a hGH recipient was reported, resulting in an immediate ban in the use of hGH in the UK.  Until the introduction of this ban, over 1,800 patients in the UK had received hGH treatment. These patients were duly informed they were at increased risk of developing CJD.  Since 1985, 80 cases of iCJD in recipients of hGH have been reported in the UK, and this number continues to increase with time. While treatment with hGH contaminated with prions is the presumed cause of iCJD in these patients, the presence of prion protein aggregates in the hGH preparations used to treat these patients has not been investigated.

Our study will investigate for the first time a unique and extensive archive of hGH preparations for the presence of prions.  Samples will be analysed using two highly sensitive methods based on different principles for amplifying and detecting prion aggregates.

This study will establish whether prions can be detected in the batches of hGH, and whether the presence of detectable prions relates to current information on which batches were most likely to have resulted in iCJD in the recipient patients. A public health aspect of this study is that this information may allow us to reassess the number of patients that remain at risk of developing iCJD. This study will also deepen our general understanding of the UK iCJD epidemic, the susceptibility of hGH preparation  methods to prion contamination, and the molecular basis of person-to-person prion transmission.

Research update at 2023 FSM: https://www.youtube.com/watch?v=uWot-3US7us&list=PLOr7SrmKCbiBq5KFO541bCC3N6f8nVHOy&index=3

Dr Alexander Peden ‘Using hsPMCA to analyse cerebrospinal fluid samples from patients with an unconfirmed diagnosis of sporadic CJD to search for possible missed cases of variant CJD’

Prion diseases are rare but devastating neurodegenerative diseases that always result in the death of the patient. Most cases of prion disease occur spontaneously, but some cases are inherited, and some are caused by transmission from other humans or animals. For instance, vCJD in humans was most likely caused by contaminated meat, following an epidemic of BSE in cattle in the 1990s.

Unfortunately, we are a long way from a cure for prion diseases, but an important step towards treatment is to understand the mechanisms of these diseases and to detect and diagnose the subtypes that are known to exist.

The only way to confirm diagnosis is by autopsy examination, and the rate of autopsies has been declining in the UK. However, a very powerful molecular technique called RT-QuIC can be used to analyse cerebrospinal fluid from patients. This is very good at detecting the spontaneous forms of prion disease (sporadic CJD), but it cannot detect other subtypes including vCJD. Fortunately, our lab has developed another molecular technique, called hsPMCA, that can detect vCJD in CSF samples

We want to see if we can use hsPMCA to rule out the possibility of missed vCJD cases, and to see if hsPMCA can be used going forward, to look at CSF samples for patients where we are unsure of the diagnosis. This will reassure us that we are doing everything possible to detect and diagnose all cases and subtypes of prion disease.

Research introduction at 2023 FSM: https://www.youtube.com/watch?v=n4aYwEKi0uI&list=PLOr7SrmKCbiBq5KFO541bCC3N6f8nVHOy&index=4

Dr Edgar Chan ‘Evaluation of single-session ACT to support those living at-risk of Prion disease.’

Living at-risk of prion disease can cause significant psychological burden, regardless of the decision to undergo testing and its results. A small study recently showed that symptoms of anxiety and depression was equally high in at-risk individuals who did not undergo testing, mutation carriers, and noncarriers (Schwartz et al., 2019). This is also reflected in what we have observed in our clinical experience at the NPC. Prolonged psychological difficulties can have a pervasive impact on well-being and quality of life, everyday functioning, work productivity, relationship with others, as well as physical health. There is currently little to no research addressing how to support patients psychologically to cope with living at risk.

This project will be the first to address this concern using a randomised control methodology. If deemed effective, this novel intervention will improve psychological outcomes for those living at risk of prion disease and provide evidence on how to support future patients. Moreover, it may have a broader, systemic impact by teaching those at risk of prion disease more effective coping strategies which can then be passed on generationally. In addition, the single-session group workshop format may prove to be a feasible and cost-effective approach and has the potential to inform practice in a range of other patient groups across NHS services.

Research introduction 2023 FSM: https://www.youtube.com/watch?v=mRYWvYIDXWQ&list=PLOr7SrmKCbiBq5KFO541bCC3N6f8nVHOy&index=5

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