Human cell based assays to study the immunopathology of the inflammatory neuropathies
Lead Research Organisation:
University of Oxford
Department Name: Clinical Neurosciences
Abstract
The inflammatory neuropathies occur when a person's immune system mistakenly attacks their own peripheral nerves. These nerves carry instructions to the muscles and sensations from the skin. When they are damaged weakness and numbness result. In severe cases a patient can lose their ability to walk, swallow and breathe. Guillain Barré syndrome (GBS) is the most common acute inflammatory neuropathy. It affects around 1200 people in the UK each year, and each of us has a 1 in 1000 chance of developing the disease during our lifetime. GBS tends to follow an infection such as a cold or tummy bug, and has recently been associated with the Zika virus. The disease comes on over a few days, but patients can require intensive care treatment for weeks, and often need to stay in hospital for months. About 1 in 20 people die during their illness, and many do not fully recover their previous level of function even years later. Chronic types of inflammatory neuropathy come on over longer periods (typically months), frequently relapse, and often require long term treatment with steroids, infusions or chemotherapy. Treatments for these diseases are only partly effective and have not improved in over 20 years. Part of the problem is that it is still not known exactly how the immune system damages nerves. Previously, researchers have used chemical tests and animals to try and detect and study antibodies which might be attacking the nerves. There are several reasons why these approaches could be misleading. Even if antibodies are detected, they may not bind to nerves in the human body. Even if they do, they may not injure the nerves. Animal nerves, processed tissue samples and extracted chemical are different to human nerves themselves.
Recently, scientists have learned how to generate stem cells from human skin. Stem cells have a special ability to turn into all of the different cell types in the body, including those of the nervous system. I have used stem cells to grow human peripheral nerve cells in dishes in the laboratory. These cells offer a great opportunity to improve the way we study the inflammatory neuropathies. They are from human rather than animal tissue, and form the structures found in normal nerves. They can also be produced in large numbers for multiple experiments without the need to use animals.
In the proposed study I will collect blood samples from patients with different neuropathies and apply these to the dishes of human nerve cells. I will be able to see if antibodies bind to the nerves and look at how the nerves are injured. I will look at different nerve cells alone in in combination, to see if and how some are protected from or sensitised to injury. Using specially coated magnetic beads, the chemical target being attacked by the antibody will be identified. The nerve cells can also be used to see the extent to which antibodies and patients' blood samples prevent or slow nerve regrowth.
The proposed study has a number of potential benefits. Understanding how the nerves are injured might help develop new treatments, and the nerve cell cultures would also be a useful way to test these treatments in future. Identifying antibodies would allow new blood tests to be developed to improve diagnosis. Detecting specific antibodies may also indicate that a particular treatment is more (or less) likely to be effective. The ability to detect whether blood samples continue to injure nerves or prevent repair after initial therapy might indicate that more intensive treatment should be given.
Recently, scientists have learned how to generate stem cells from human skin. Stem cells have a special ability to turn into all of the different cell types in the body, including those of the nervous system. I have used stem cells to grow human peripheral nerve cells in dishes in the laboratory. These cells offer a great opportunity to improve the way we study the inflammatory neuropathies. They are from human rather than animal tissue, and form the structures found in normal nerves. They can also be produced in large numbers for multiple experiments without the need to use animals.
In the proposed study I will collect blood samples from patients with different neuropathies and apply these to the dishes of human nerve cells. I will be able to see if antibodies bind to the nerves and look at how the nerves are injured. I will look at different nerve cells alone in in combination, to see if and how some are protected from or sensitised to injury. Using specially coated magnetic beads, the chemical target being attacked by the antibody will be identified. The nerve cells can also be used to see the extent to which antibodies and patients' blood samples prevent or slow nerve regrowth.
The proposed study has a number of potential benefits. Understanding how the nerves are injured might help develop new treatments, and the nerve cell cultures would also be a useful way to test these treatments in future. Identifying antibodies would allow new blood tests to be developed to improve diagnosis. Detecting specific antibodies may also indicate that a particular treatment is more (or less) likely to be effective. The ability to detect whether blood samples continue to injure nerves or prevent repair after initial therapy might indicate that more intensive treatment should be given.
Technical Summary
The inflammatory neuropathies are significant causes of morbidity and mortality with sub-optimal diagnostic algorithms, biomarkers and treatments. Previous research has relied heavily on solid phase assays and animal models, with limited success. The proposed study aims to extend understanding of inflammatory neuropathy pathogenesis, improve diagnostic assays, and better guide future treatment decisions. This objective will be achieved by identifying pathogenic mechanisms and antibodies using human induced pluripotent stem cell (hiPSC) derived sensory neurons, spinal motor neurons, Schwann cells and myelinating co-cultures. The topographical pattern of antibody binding will then be assessed without a priori specification of putative molecular targets. Pathological processes and regeneration will be studied over longer time periods than is possible in other systems. Co-cultures will allow assessment of the deleterious effects of patient derived serum on axo-glial interactions and myelination. Factors modulating or protecting from injury, such as antibody internalisation, and complement activation and regulation, will be evaluated. Antigen targets will be identified by immunoprecipitation and mass spectrometry. Detected antibody specificities and neuropathological activity will then be linked back to key clinical features such as prognosis and the response to particular treatments. Specific hypotheses that will be addressed in the proposed research are; i) comparing sensory and motor neurons, and control and disease-associated cells, will identify reasons for the selective and regional sensitivity of specific peripheral nerve tissue to immune mediated injury, ii) cell based assays will offer improved diagnostic sensitivity and specificity, iii) patients whose serum show persistent neuropathic potential in culture are likely to continue to progress and/or recover more slowly, providing a biomarker to identify those most likely to benefit from additional treatment.
Planned Impact
Who will benefit from this research?
The research will benefit my professional development, and also provide post-doctoral training in stem cell, immunological and peripheral nerve research for another individual. Other beneficiaries of this work will be investigators working in related fields, but also those with interests in a range of other areas, such as;
a) other researchers studying immune mediated neuropathies
b) investigators studying other neurological and non-neurological antibody mediated, or potentially antibody mediated, diseases
c) scientists interested in other neuropathies, including those which are genetically mediated
d) researchers looking at the biology of peripheral nerves, their repair processes, and strategies for enhancing these
e) those studying other non-antibody lectin-glycolipid interactions (eg. bacterial toxins and sialic-acid binding immunoreceptors)
Within the commercial sector potential beneficiaries include;
a) companies developing diagnostic immunoassays
b) pharmaceutical companies developing
i. new immunotherapies
ii. neuroprotective agents in a more general sense
iii. agents promoting nerve repair/regeneration
Within the health service and amongst regulators, potential beneficiaries include;
a) those involved in the planning of neurology inpatient and neurorehabilitation provisions
b) those involved in approving and rationing expensive treatments (eg. intravenous immunoglobulin (IVIg))
Charitable beneficiaries include;
a) The GBS and Associated Inflammatory Neuropathies (GAIN) charity
Ultimately, neuropathy patients will also benefit.
How will they benefit from this research?
I will gain personal experience in leading an independent research programme, and managing other staff. I will supervise a post-doctoral researcher, who will themselves gain experience of stem cell, peripheral nerve and neuroimmunological research. We will also both benefit from exposure to the wider programme of research activity within the department. My continued involvement in inflammatory neuropathy research will allow me to continue to provide up to date expert medical advice to the GAIN charity. The specific research proposed addresses some questions which have been relatively neglected to date - namely, what factors modulate antibody-antigen interactions within the living membrane, and what sensitises or protects nerves from antibody mediated injury? It will also result in fully humanised assay platforms which should offer enhanced sensitivity and specificity for detecting disease associated antibodies and assessing neuropathological effects. The development and subsequent clinical application of serological tests may improve diagnosis and prognostication, reduce the need for invasive tests such as nerve biopsy, allow the selection of patients who will benefit from treatments such as IVIg, avoid the need for a treatment trial in those who will not benefit, or provide impetus to initiate or escalate treatment in others. The research focus on factors modulating antibody mediated injury may suggest new strategies for abrogating this. The use of human cultures as a model system for inflammatory neuropathies offers a more cost effective way of trialling new immunomodulatory or neuroprotective therapies, unreliant on experimental animals. The efficiency and cost-effectiveness of screening such therapies would be improved. Furthermore, the core methodology could be used to enhance understanding of other causes of neuropathy. It would provide genetic neuropathy researchers with a relevant platform in which to assess the pathogenic mechanisms and importance of detected mutations, something which is not easily assessed by sequencing data alone. The cell based assays would provide a powerful tool for researchers to study some of the process of peripheral nerve regeneration and allow multiple strategies for enhancing this to be evaluated in parallel.
The research will benefit my professional development, and also provide post-doctoral training in stem cell, immunological and peripheral nerve research for another individual. Other beneficiaries of this work will be investigators working in related fields, but also those with interests in a range of other areas, such as;
a) other researchers studying immune mediated neuropathies
b) investigators studying other neurological and non-neurological antibody mediated, or potentially antibody mediated, diseases
c) scientists interested in other neuropathies, including those which are genetically mediated
d) researchers looking at the biology of peripheral nerves, their repair processes, and strategies for enhancing these
e) those studying other non-antibody lectin-glycolipid interactions (eg. bacterial toxins and sialic-acid binding immunoreceptors)
Within the commercial sector potential beneficiaries include;
a) companies developing diagnostic immunoassays
b) pharmaceutical companies developing
i. new immunotherapies
ii. neuroprotective agents in a more general sense
iii. agents promoting nerve repair/regeneration
Within the health service and amongst regulators, potential beneficiaries include;
a) those involved in the planning of neurology inpatient and neurorehabilitation provisions
b) those involved in approving and rationing expensive treatments (eg. intravenous immunoglobulin (IVIg))
Charitable beneficiaries include;
a) The GBS and Associated Inflammatory Neuropathies (GAIN) charity
Ultimately, neuropathy patients will also benefit.
How will they benefit from this research?
I will gain personal experience in leading an independent research programme, and managing other staff. I will supervise a post-doctoral researcher, who will themselves gain experience of stem cell, peripheral nerve and neuroimmunological research. We will also both benefit from exposure to the wider programme of research activity within the department. My continued involvement in inflammatory neuropathy research will allow me to continue to provide up to date expert medical advice to the GAIN charity. The specific research proposed addresses some questions which have been relatively neglected to date - namely, what factors modulate antibody-antigen interactions within the living membrane, and what sensitises or protects nerves from antibody mediated injury? It will also result in fully humanised assay platforms which should offer enhanced sensitivity and specificity for detecting disease associated antibodies and assessing neuropathological effects. The development and subsequent clinical application of serological tests may improve diagnosis and prognostication, reduce the need for invasive tests such as nerve biopsy, allow the selection of patients who will benefit from treatments such as IVIg, avoid the need for a treatment trial in those who will not benefit, or provide impetus to initiate or escalate treatment in others. The research focus on factors modulating antibody mediated injury may suggest new strategies for abrogating this. The use of human cultures as a model system for inflammatory neuropathies offers a more cost effective way of trialling new immunomodulatory or neuroprotective therapies, unreliant on experimental animals. The efficiency and cost-effectiveness of screening such therapies would be improved. Furthermore, the core methodology could be used to enhance understanding of other causes of neuropathy. It would provide genetic neuropathy researchers with a relevant platform in which to assess the pathogenic mechanisms and importance of detected mutations, something which is not easily assessed by sequencing data alone. The cell based assays would provide a powerful tool for researchers to study some of the process of peripheral nerve regeneration and allow multiple strategies for enhancing this to be evaluated in parallel.
People |
ORCID iD |
Simon Rinaldi (Principal Investigator / Fellow) |
Publications
Arends S
(2022)
Electrodiagnosis of Guillain-Barre syndrome in the International GBS Outcome Study: Differences in methods and reference values.
in Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology
Clark AJ
(2017)
Co-cultures with stem cell-derived human sensory neurons reveal regulators of peripheral myelination.
in Brain : a journal of neurology
Davies AJ
(2019)
Natural Killer Cells Degenerate Intact Sensory Afferents following Nerve Injury.
in Cell
Davies AJ
(2023)
Guillain-Barré Syndrome Following Zika Virus Infection Is Associated With a Diverse Spectrum of Peripheral Nerve Reactive Antibodies.
in Neurology(R) neuroimmunology & neuroinflammation
Davies AJ
(2020)
Immunoadsorption and Plasma Exchange in Seropositive and Seronegative Immune-Mediated Neuropathies.
in Journal of clinical medicine
Davies AJ
(2020)
Cytotoxic Immunity in Peripheral Nerve Injury and Pain.
in Frontiers in neuroscience
Davies Alexander
(2020)
Zika virus infection raises antibodies against multiple peripheral nerve antigens
in JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM
Davies Alexander
(2021)
Myelinated, human stem cell-derived sensory neurons for screening for the presence of peripheral nerve-reactive autoantibodies in patient sera
in JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM
Description | Member of commissioning review board for rituximab in anti-MAG neuropathy |
Geographic Reach | National |
Policy Influence Type | Contribution to a national consultation/review |
Impact | Rituximab now improved fro treatment of anti-MAG neuropathy |
Description | Neuropathy referral guide for GPs |
Geographic Reach | Local/Municipal/Regional |
Policy Influence Type | Influenced training of practitioners or researchers |
Description | New NHSE commissioning policy - Rituximab therapy for the treatment of nodal/paranodal antibody positive inflammatory/autoimmune neuropathy in adults and postpubescent children |
Geographic Reach | National |
Policy Influence Type | Contribution to a national consultation/review |
Impact | Effective medicine made accessible to patients. |
URL | https://www.england.nhs.uk/publication/rituximab-therapy-for-the-treatment-of-nodal-paranodal-antibo... |
Description | Submitted application for commissioning of rituximab in IgG4-mediated CIDP |
Geographic Reach | National |
Policy Influence Type | Contribution to a national consultation/review |
Description | ABN Research Training Fellowship (as supervisor to Dr Stephen Keddie) |
Amount | £218,094 (GBP) |
Organisation | Association of British Neurologists (ABN) |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 08/2017 |
End | 08/2020 |
Description | Benson Fellowship (as supervisor to Dr Janev Fehmi) |
Amount | $313,661 (USD) |
Organisation | GBS/CIDP Foundation International |
Sector | Charity/Non Profit |
Country | United States |
Start | 02/2019 |
End | 02/2022 |
Description | COVID-19 Research Response Fund - A study to establish the frequency and mechanism of COVID-19- related inflammatory neuropathies |
Amount | £93,106 (GBP) |
Organisation | University of Oxford |
Sector | Academic/University |
Country | United Kingdom |
Start | 07/2020 |
End | 08/2022 |
Description | Guarantors of Brain Pre-Doctoral Fellowship (as supervisor to Dr Janev Fehmi) |
Amount | £60,000 (GBP) |
Organisation | Guarantors of Brain |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 08/2018 |
End | 02/2019 |
Description | Identifying, characterising and evaluating antibodies in Guillain-Barré syndrome |
Amount | £436,465 (GBP) |
Funding ID | MR/X003922/1 |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 11/2022 |
End | 11/2025 |
Description | John Fell Fund - Zika infection and autoimmune peripheral neuropathy |
Amount | £7,500 (GBP) |
Organisation | University of Oxford |
Sector | Academic/University |
Country | United Kingdom |
Start | 06/2018 |
End | 05/2019 |
Description | Little Princess Trust Project Grants - Reducing neurotoxicity of immunotherapies by glycan modification of monoclonal antibodies |
Amount | £33,854 (GBP) |
Funding ID | 2021BLPT19 |
Organisation | Little Princess Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 04/2022 |
End | 04/2023 |
Description | Vera Down - Cloning neuropathy-related human monoclonal antibodies to develop precision immunotherapies |
Amount | £65,000 (GBP) |
Organisation | British Medical Association (BMA) |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 09/2022 |
End | 09/2025 |
Title | Cloning of neuropathy associated human antibodies |
Description | ASCs secreting a particular Ig class can be enriched by first bulk-sorting ASCs from whole PBMCs by sequential CD3-/CD19+/CD20low/- and CD38high/CD27high gating for single cell sorting. If previous experiments demonstrate that B cells with the specificity of interest are not detected in the circulating ASC pool and are instead contained within a more immature B-cell population, then gating and sorting strategies will be adjusted as appropriate. Furthermore, with a known target and biotin-tagged antigen "bait", it is possible to substantially enrich the frequency of sorted cells which display the antibody specificity and auto-reactivity of interest. Whichever strategy is used, purified cells will be single-cell sorted into individual wells of single-cell PCR plates and clonally expanded in culture. Reverse-transcriptase (RT) PCR will then be employed to generate cDNA from mRNA, using a mix of primers designed to amplify all possible variable (V) region antibody genes. Nested PCR will subsequently be used to amplify the heavy and light-chain V genes in order to facilitate sequencing. This in turn will inform the cloning PCR, in which V-family specific primers are used to further amplify the DNA, and place the VDJ-heavy and VJ-light sequences in frame with the constant-region sequences in the cloning/expression vectors, typically by use of sequence and ligation independent cloning (SLIC). In this way separate heavy and light-chain containing vectors can be produced, transformed, and co-transfected to drive complete antibody production. Sequence data from the PCR products will be used to establish the VH and VL germline references, providing information about the original immunoglobulin class, subclass, and light-chain isotype (kappa or lambda). Complementarity-determining (CDR3) sequences and percentage homology to germline will also be evaluated to assess the role of somatic hypermutation in producing antibodies with these affinities. For large-scale production, antibodies in culture supernatants from co-transfected cells will be protein A/G purified and concentrated as required. Antibody specificities will be confirmed using a combination of ELISA, live-transfected cell, myelinating co-culture and tissue-based assays. |
Type Of Material | Antibody |
Year Produced | 2019 |
Provided To Others? | No |
Impact | Will begin to be realised over the coming year. |
Title | Nodal / paranoidal antibody testing using transfected cell based assay |
Description | 1. HEK293 (Human embryonic kidney) cells in 10% FBS (fetal bovine serum) in DMEM (Dulbecco modified Eagle culture medium) are plated on Poly-L-Lysine-coated coverslips in 24 multiwell culture plates (Greiner Cellstar ?) and incubated for 24 hours at 37?C 2. At ~80% confluence HEK cells were singly transfected with DNA plasmids encoding either NF155 or NF186, or co-transfected with CNTN1/Caspr (Courtesy of Lus Querol), using JetPEI? Transfection reagent (Polyplus transfection) 3. After 48 hours cells incubated for 1 hour at room temperature with patient sera. Sera (1:100), with chicken anti-neurofascin antibody** (R&D Systems AF 3235) (1:1000) was diluted in DMEM/HEPES/1%BSA* for incubation with all neurofascin transfected cells; Sera (1:40) in DMEM/HEPES/1%BSA for incubation with all CNTN/Caspr transfected cells 4. These were washed with 3 changes of DMEM/HEPES then fixed with 4% paraformaldehyde in PBS (phosphate-buffered saline) for 5 mins, before washing in PBS 5. Coverslips were then incubated with Secondary antibodies for 45 minutes at room temperature in the dark: a. Goat anti-chicken IgY (H+L) Alexa Fluor 546 (Thermo Fisher Scientific) b. F(ab')2-Goat anti-human IgG Fc Alexa Fluor 488 (Thermo Fisher Scientific) 6. Finally they were washed with DMEM/HEPES and PBS, then incubated with DAPI (4',6-diamidino-2-phenylindole) (1:50000) for 5 mins at room temperature in the dark 7. Coverslips were imaged immediately after |
Type Of Material | Technology assay or reagent |
Year Produced | 2018 |
Provided To Others? | Yes |
Impact | Testing of samples from >300 patients. Identification has impacted on treatment and improved clinical outcomes. |
Title | Bio-SPIN |
Description | A clinico-serological database of acute and chronic inflammatory neuropathy patients. |
Type Of Material | Database/Collection of data |
Year Produced | 2018 |
Provided To Others? | No |
Impact | Additional identification of link between CNTN1 antibodies and nephrotic syndrome. Source of PBMCs for human antibody cloning. |
Description | Dr Alistair Easton (Southampton), Dr Ben Davies (Oxford) - anti-GD2 antibody neurotoxicity and modification through glyco-engineering |
Organisation | University of Oxford |
Department | Department of Chemistry |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Assessing anti-GD2 antibodies and their deglycosylated forms for peripheral nerve toxicity. |
Collaborator Contribution | AE - provision of unmodified antibody, assessment of anti-tumour effects. BD - modification of antibody. |
Impact | Data generation ongoing Abstract in JPNS and poster presentation at PNS 2018 (Baltimore) |
Start Year | 2017 |
Description | Dr Alistair Easton (Southampton), Dr Ben Davies (Oxford) - anti-GD2 antibody neurotoxicity and modification through glyco-engineering |
Organisation | University of Southampton |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Assessing anti-GD2 antibodies and their deglycosylated forms for peripheral nerve toxicity. |
Collaborator Contribution | AE - provision of unmodified antibody, assessment of anti-tumour effects. BD - modification of antibody. |
Impact | Data generation ongoing Abstract in JPNS and poster presentation at PNS 2018 (Baltimore) |
Start Year | 2017 |
Description | Dr David Bennett - Myelinating co-cultures |
Organisation | University of Oxford |
Department | Nuffield Department of Clinical Neurosciences |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Provision of monoconal antibodies and serum samples for use in myelinating co-culture / cell based assays. NF155 sera used to specifically identify NF155 at paranodes Use of cultures for antibody detection and pathogenesis studies |
Collaborator Contribution | Technical support for dorsal root ganglion and sensory neuron induced pluripotent stem cell myelinating co-cultures. |
Impact | Brain paper 2017 (Clark) Figures using this technique will from part of CNTN1 and Zika papers in preparation |
Start Year | 2013 |
Description | Dr Luis Querol - NF155 / CNTN / CASPR studies |
Organisation | University College Hospital |
Country | United Kingdom |
Sector | Hospitals |
PI Contribution | Use of NF155 and CASPR serum in myelinating co-cultures. CBA for antibody detection Contribution of DNA samples from CNTN1 +ve patients to HLA study Co-ordination of CNTN1 +ve CIDP / nephrotic cohort |
Collaborator Contribution | Provision of NF155 and CASPR positive sera. |
Impact | CNTN1 / nephrotic abstract and poster at PNS 2018 3 abstracts submitted to PNS 2019 (Genoa) - publications to follow |
Start Year | 2016 |
Description | Hugh Willison / Luis Querol - Zika-GBS |
Organisation | University of Glasgow |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Analysis of Zika-GBS sera and controls over myelinating co-cultures |
Collaborator Contribution | Collection and distribution of sera and clinical data Parallel analysis on glycoarray and primary cells |
Impact | Data being collected and analysed for future publicaiton Abstract submitted to PNS meeting (Genoa, 2019) |
Start Year | 2018 |
Title | Therapeutic Rituximab in CIDP (The TRIC Trial) |
Description | Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a condition in which a person's immune system mistakenly attacks and damages their nerves. Sufferers typically lose their strength and balance. This often makes simple day-to-day tasks difficult or even impossible. Current treatments can be effective, but many patients do not recover fully. Most require long-term therapy. This often means monthly attendance at hospital for infusions of a blood product known as intravenous immunoglobulin. This treatment can temporarily prevent the immune system from damaging nerves, but does not address the underlying cause of the problem. In contrast, rituximab is a medicine which targets and destroys the immune cells thought to be important in causing CIDP. This treatment has already been used in small numbers of CIDP patients. It can be very effective, with some patients going into remission for many years after a pair of infusions given 2 weeks apart. However, the evidence is currently not felt to be strong enough for rituximab to be approved by NICE for use in the UK for CIDP treatment. We therefore intend to set up the first clinical trial to find out whether rituximab is clinically effective, safe and cost effective in CIDP. We have already assessed whether such a trial would be of interest to patients with CIDP and their treating doctors, what trial design would be acceptable, and what potential benefits would be most important to them. We did this by sending out an information sheet and questionnaire to CIDP patients registered on the GAIN (Guillain-Barré syndrome and Associated Inflammatory Neuropathies) charity database. 31/40 respondents (77.5%) indicated they would be willing to be involved in a trial of rituximab. They told us that an improved ability to carry out certain day-to-day tasks, followed by an ability to reduce or stop existing therapies, would be the most important benefits to assess. Patients also told us that a trial design where they would definitely receive rituximab at some point would make them more likely to sign up. We have now additionally asked some patients for feedback on the more detailed trial protocol and this summary. We will also involve patients in the production of trial information sheets and consent forms. Informed by existing patient involvement, we have designed a trial which looks at whether rituximab leads to either an improved ability to carry out certain day-to-day tasks or allows existing treatments to be stopped (or both). Day-to-day abilities will be measured by a questionnaire-based scale which has been specifically designed for and validated by CIDP patients. This scale is also more sensitive for detecting meaningful improvement or worsening in CIDP than other measures used in the past. Patients who initially receive the "dummy drug" (placebo) but then re-deteriorate when their existing treatment is again interrupted will also receive rituximab. This trial is likely to influence the treatment of CIDP patients around the world. If effective, rituximab would reduce attendances at hospital, reduce the use of scarce immunoglobulin resources, reduce drug costs, and improve patients' quality of life. The results will be published in international scientific journals, brought to the attention of the media via a press release, and communicated to patients via the UK GAIN and international CIDP charities. |
Type | Therapeutic Intervention - Drug |
Current Stage Of Development | Refinement. Clinical |
Year Development Stage Completed | 2019 |
Development Status | Actively seeking support |
Impact | Creation of a wider CIDP disease database and bio-bank. Improving the care and outcome of patients with CIDP. |
Title | UK diagnostic testing of nodal/paranodal antibodies |
Description | i set up diagnostic testing for nodal/paranodal antibodies within the UK and our lab has since testing over 700 samples. |
Type | Diagnostic Tool - Non-Imaging |
Current Stage Of Development | Small-scale adoption |
Year Development Stage Completed | 2019 |
Development Status | Under active development/distribution |
Impact | Has also had a positive impact on research. |
Description | Brain Diaries - Public Engagement Event - Oxford March 2017 |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | 2 days of interactive activities looking at the tactile senses aimed at children. |
Year(s) Of Engagement Activity | 2017 |
URL | http://www.oum.ox.ac.uk/braindiaries/ |
Description | Stroyville - Breaking the silence |
Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | Documentary on inflammatory neuropathy on which I appeared and acted as medical advisor. |
Year(s) Of Engagement Activity | 2019,2020,2021 |
URL | https://www.bbc.co.uk/news/business-54961058 |