The National Prion Clinic (NPC) is the national referral centre for prion disease and is part of the University College London Hospitals NHS Foundation Trust (UCLH). It is funded by the NHS to provide diagnosis and care for patients with, or suspected to have, any form of human prion disease (Creutzfeldt-Jakob disease, CJD). The clinic is integrally linked with the MRC Prion Unit at the Institute of Neurology, a Postgraduate Research Institute of University College London. The NPC provides diagnosis and care for all forms of prion disease (inherited, iatrogenic, sporadic and variant CJD). We aim to review new patients within a week of referral. The NPC also plays a key role in facilitating research to promote early diagnosis and the development of potential therapies.
The following sections provide information on prion disease, the services we offer and research into prion disease (CJD).
Prions cause lethal neurodegen-erative diseases in mammals and are composed of multichain assemblies of misfolded host-encoded cellular prion protein (PrP). A common polymorphism at codon 129 of the PrP gene (PRNP), where either methionine (M) or valine (V) is encoded, affects the susceptibility to prion disease, as well as the incubation period1 and clinical phenotype of prion disease.
The MRC Prion Unit has been conducting a long-term clinical study on prion diseases in the UK as part of its research to develop effective treatments for these conditions. In the course of this research, we perform detailed studies on brain samples where patients and their families consent to donate tissue for our research. Recently, we looked at eight patients who had developed CJD after treatment with growth hormone. Surprisingly, we found that four had significant or severe changes in their brains normally seen in Alzheimer’s disease (AD) which are very rarely seen in patients of this age group.
National Prion Clinic describe a new form of inherited prion disease that causes diarrhoea
Prion diseases usually cause problems with balance and thinking skills due to damage in the brain and other parts of the central nervous system. They are caused by a normal body protein, called the prion protein, changing shape, depositing in brain tissue, and becoming toxic to nerve cells (Background to Prion Disease). The National Prion Clinic team now report the investigation of a new disease in a single large family, caused by a gene mutation. This gene mutation makes a short version of the prion protein and uncouples it from attachment to the surface of cells. The newly identified prion disease is unusual because the symptoms start with diarrhea. The symptoms typically commence when patients are in their thirties, and then over the next 10 years the symptoms gradually progress and involve loss of sensation in the feet, and low blood pressure on standing. It is only 20 years later that problems with thinking skills start. Deposits of abnormal prion protein were found throughout the body, for example, in the gut, nerves, heart, and lungs. Doctors should now be aware that if they have a patient with unexplained diarrhea and signs of a neuropathy it’s worth checking the prion protein gene for abnormalities.
National Prion Clinic develop a new way to measure progression in prion disease: the MRC Scale
The National Prion Clinic team have developed a rating scale for prion diseases, that will have major implications in future treatment trials. In a paper published in the top neurological scientific journal Brain, the team describe a precise way to track how patients with prion disease are progressing.
The use of the MRC Prion Disease Rating Scale or “MRC Scale” in short form, in the National Monitoring Prion Cohort has revealed there are three distinct patterns of change: 1. slow progression associated with genetic forms of disease, 2. rapid progression associated with any form of the disease, and 3. a proportion of patients that survive in a comatose state sometimes for prolonged periods of time.
The paper is based on follow-on work from a MRC funded clinical trial PRION-1 (2004-2007), using the anti-malarial drug – quinacrine, which concluded that there was a need for a definitive prion disease rating scale. The PRION-1 study raised lots of questions, in particular about how to measure the progress of patients through the disease. Some rating scales we have used in the past were poor at measuring patient progression, though questions about every-day activities seemed to match clinical reality. The new rating scale is based on interviews with 71 families, we’ve taken into account the experience of the disease from the perspective of patients, their relatives and carers to find out what are the important symptoms of the disease. Questions focus on speech, memory, continence, mobility and self-care, which are all important aspects of how the disease impacts on families. We appreciate and acknowledge the contribution of carers and relatives to this research work.
The Science and Technology Committee held an oral evidence session on variant Creutzfeldt-Jakob Disease (vCJD) and the ongoing risk it poses to the UK at which Prof. John Collinge gave evidence.
Briefing note for patients, carers and health professionals