The invitation to apply for a research grant (scientific or clinical) in the field of Gaucher disease appears in Gaucher News and our website. All applications are externally refereed and peer reviewed. All peer reviewed applications are presented to the board of Directors for final approval.
People with Gaucher and some of their family members carry the GBA gene. There is a slighter higher chance of developing Parkinson’s in later life if you carry this genetic alteration, but this is still a very low risk and most people do not develop Parkinson’s.
The research team at the Royal Free Hospital and University College London, led by Professors Anthony Schapira, Atul Mehta and Derralynn Hughes have over the last 6 years been investigating variation in the GBA gene and what it can tell us about Parkinson’s. The research team is currently observing associated patterns of movement, memory, sleep, mood and sense of smell using an online study portal. The aim is to intervene much earlier before the movement symptoms associated with Parkinson’s ever develop and to protect the nerve cells in the brain.
With the generosity of time and help of people with Gaucher, their research has now led to a phase II drug trial of Ambroxol, a drug traditionally used as a respiratory medication which has been showing very promising neuroprotective qualities.
Recruitment started last year in 2016 on the RAPSODI study. So far over 200 people with Gaucher disease and their families have done the online portal, mainly from the Lysosomal Storage Disorders Unit at the Royal Free in London. People are now being invited to take part from the other centres around the country. The study takes about 45 minutes to do on your computer or laptop at home and then some postal tests.
You can visit the study portal to see more about the research www.rapsodi.org.uk. If you would like to take part or learn more, please contact Dr Marco Toffoli at rapsodi@ucl.com
The National GAUCHERITE Project (Gaucher disease Investigative Therapy Evaluation) is an on-going wide-scale observational ‘cohort’ study of Gaucher disease in the UK. This project has been principally funded as the first, and so far only, genetic disorder included in the Medical Research Council’s burgeoning Stratified Medicine research portfolio.
We are exploring the outcomes of treatments and quality-of-life benefits with multivariate disease stratification to define distinct types of disease behaviour. This approach is now believed to be one of the best means of tailoring treatments in particular patients with particular therapies. It also should lead to greater understanding and accurate prediction of disease behaviour and inform better decisions about treatment.
Our participants with Gaucher disease (aged 5 years and over) attend the eight National Specialist Centres for the advanced treatment and monitoring of Gaucher disease. As of December 2016, and now in its last year of funding from the MRC, 209 patients including 17 children have enrolled. This is a wonderful testament to the engagement of the whole community who already contribute hugely to research efforts across the UK and abroad.
GAUCHERITE involves the collection, assembly and collation of detailed clinical and pathological information. This includes historical and present outcomes from serial DEXA and other radiological imaging, as well as haematological, biochemical and genetic data in the ultra-deep characterization of UK patients recorded with all medication. The Programme is also curating a single bespoke Biobank, holding deep-frozen plasma, sera, frozen blood cells DNA and other diverse clinical material, for further research.
The project includes two special research strands for paediatric and adult patients. The first is the osseous which involves bone problems and the skeleton including multiple myeloma. The second is the neurological strand involving Parkinsonism and also many ill-understood clinical aspects of the neurological effects of Gaucher disease (so-called ‘type 3’) affecting adults and children.
This is now a time for taking stock of all the (fully anonymized) information we have collected in a special dedicated and easy to use data resource designed especially for GAUCHERITE to provide information for public release. With this in mind, the next step will be a formal interim analysis – funding for which is being currently sought from one of our supporting companies who have signed collaborative agreements with the MRC.
In the light of the findings and the critical importance of the future outcomes of the programme, there is no doubt that the project will have lasting value in directing future therapeutic initiatives for the benefit of all patients. To this effect, we are looking to the future to maintain the database and the services of our excellent clinical manager and Clinical Research Fellows as well as the resource of blood cells and other material in the Biobank in Oxford. Everyone at every level – service directors, nurses, doctors, secretaries, clerks, database managers and handlers, radiologists and scientists – has done a fantastic job despite the terrible pressures currently in the NHS.
It is striking that we have had the fullest engagement at our research away day and at the management consortium meetings from first-rate and senior representatives of the biopharmaceutical industry. The presence of Actelion, Sanofi Genzyme and Shire at consortium meetings has been a model of collaboration and disinterested scientific behaviour at every level; our industrial collaborators have given constructive assistance freely with an excellent following at each of many meetings up and down the country. So far little money has changed hands – but know-how and ideas have been generously shared to the huge benefit of the work!
While we have some way to go, massive strides have been made: at least 80% of the UK patient population is signed up with nearly all the children too. We are pleased to say that we have managed recently to find some funds to maintain continuity through key clinical research staff – if not yet for complete ‘future-proofing’. This has come from the Biomedical Research Centres of the National Institute for Health Research in the NHS and needs to be expanded.
In 2009 the Association gave a small grant to the Department of Haematology at the Royal Free Hospital, London, to purchase some viral vectors for use in gene therapy research in Type II Gaucher disease.
On purchasing the vectors, the department injected these into foetal and neonatal mice and found that they could deliver a marker gene very efficiently to the central and peripheral nervous system. This is an important finding because in Type II (neuronopathic) Gaucher disease the damage to the nervous system is impossible to treat using enzyme replacement therapy.
Based on preliminary results, the team applied to the UK Medical Research Council to do more extensive studies, initially with marker genes, but then using a gene therapy vector for glucocerebrosidase to treat a mouse model of Type II Gaucher disease.
The Medical Research Council has awarded them a grant of £470,000 to perform this work. This will pay for Dr Ahad Rahim to concentrate his activities on gene therapy for Type II Gaucher disease for three years. The team is extremely excited to be embarking upon these studies, particularly given the fast pace at which preclinical and clinical gene therapy is moving. For example, earlier this year, an incurable mouse model of the disease spinal muscular atrophy was completely cured by neonatal injection of a similar gene therapy vector which they are planning to use.
