Protein engineering to design better enzyme replacement therapies for Fabry disease
| ISRCTN | ISRCTN14092141 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN14092141 |
| Integrated Research Application System (IRAS) | 340344 |
| Central Portfolio Management System (CPMS) | 63395 |
| Sponsor | University of Edinburgh |
| Funder | UK Research and Innovation |
- Submission date
- 31/03/2026
- Registration date
- 28/04/2026
- Last edited
- 07/05/2026
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Nutritional, Metabolic, Endocrine
Plain English summary of protocol
Background and study aims:
Lysosomal storage disorders (LSDs) are rare, inherited metabolic disorders causing life-threatening, progressive disease affecting many body systems. They are caused by mutations in genes which code for lysosomal enzymes, which break down large toxic molecules in the cell. When these enzymes don’t work properly these substances build up, causing damage to the heart, kidneys, blood vessels, muscles, brain and skeleton, depending on which enzyme is affected. Fabry disease is the most common LSD and causes nerve pain, strokes, and progressive heart and kidney disease.
Some LSDs can be treated with enzyme replacement therapy (ERT). This involves a weekly or fortnightly infusion treatment given directly into the vein. However, current treatments are only partly effective as they work less well than natural enzymes and cannot access certain body tissues. They also cause immune reactions, leading to severe allergic-type reactions, and further reduce the effectiveness of the treatment. Patients find these side effects and the frequency of the infusions a major burden.
We are using artificial intelligence-led protein design to help design new treatments for Fabry disease. These enzymes are designed to work more effectively and not cause immune reactions. They are designed to be better than current treatments so they can be given less often and work more effectively. The first stage of testing is to see whether they cause fewer immune reactions than existing treatments. We will do this by testing them in samples of patients' blood in the laboratory.
Who can participate?
Anyone with a confirmed diagnosis of Fabry disease who is over 16 years old and is not taking any regular immune-suppression medication (such as for a kidney or heart transplant). We are not able to enrol patients who have received experimental gene therapies for Fabry disease.
What does the study involve?
We would like you to donate an extra sample of blood and urine, usually taken at a single visit at the same time as your routine NHS clinic bloods. You can also choose to have a 24-hour ambulatory blood pressure and vascular stiffness monitor, which you take home and post back to us.
What are the possible benefits and risks of participating?
There are no direct benefits to taking part, but you will be contributing to research which may help improve treatments for people with Fabry disease.
There are no significant risks to taking part: blood tests may be uncomfortable and leave a small bruise but will be taken at the same time as your usual blood tests. The 24-hour ambulatory blood pressure cuff is inconvenient but should not be painful.
Where is the study run from?
The study is being run from the Clinical Research Centre at the University of Edinburgh (UK)
When is the study starting and how long is it expected to run for?
August 2024 to December 2026
Who is funding the study?
The study has been funded by the Engineering and Physical Sciences Research Council (EPSRC) (UK)
Who is the main contact?
Dr Eve Miller-Hodges, eve.miller-hodges@ed.ac.uk
Contact information
Public, Scientific, Principal investigator
BHF Centre for Cardiovascular Science
Queen's Medical Research Institute, University of Edinburgh
47 Little France Crescent
Edinburgh
EH16 4TJ
United Kingdom
 ORCID ID |
0000-0002-7687-5781 |
|---|---|
| Phone | +44 (0)7944685620 |
| eve.miller-hodges@ed.ac.uk |
Study information
| Primary study design | Observational |
|---|---|
| Observational study design | Cross sectional study |
| Scientific title | Intelligent De-immunization of Enzyme Replacement Therapies (IDERT) |
| Study acronym | IDERT |
| Study objectives | This study aims to test the immunogenicity of novel engineered enzymes against patient samples, in order to design better treatments for patients with Fabry disease |
| Ethics approval(s) |
Approved 04/06/2024, South West - Cornwall & Plymouth Research Ethics Committee (2 Redman Place, Stratford, London, E20 1JQ, United Kingdom; +44 (0)3071048071; cornwallandplymouth.rec@hra.nhs.uk), ref: 4/SW/0061 |
| Health condition(s) or problem(s) studied | Fabry disease |
| Methodology | Collection of blood and urine samples 24-hour non-invasive home measure of blood pressure and blood vessel function (optional) |
| Intervention type | Other |
| Primary outcome measure(s) |
Cross-reactivity of existing patient anti-drug antibodies to the new designed enzymes tested using enzyme-linked immunosorbent assays (ELISA) in patient sera and reported relative to wild-type enzyme and existing treatments at a single timepoint |
| Key secondary outcome measure(s) |
Associations between immune-reactivity to the new designed enzymes compared to the clinical phenotype of the patient (defined as classical or late onset); sex; prior treatment exposure (type of enzyme replacement therapy), plasma lyso-GB3 (measured using liquid chromatography tandem mass spectrometry) and ambulatory blood pressure and vascular stiffness (measured using Mobil-o-Graph NG 24hr ABPM System) at a single timepoint |
| Completion date | 30/12/2026 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Mixed |
| Lower age limit | 16 Years |
| Upper age limit | 100 Years |
| Sex | All |
| Target sample size at registration | 30 |
| Key inclusion criteria | 1. Diagnosis of Fabry disease (biochemical and/or genetic diagnosis) 2. Aged 16 years or over 3. Able to give informed consent 4. Not on immunosuppressive medications (e.g., previous transplant) which could impact immunogenicity 5. Never received gene-therapy for Fabry disease 6. No upper age limit |
| Key exclusion criteria | 1. On immunosuppressive medication (equivalent to >7.5 mg prednisolone daily) 2. Treated with gene therapy for Fabry Disease 3. Unable to give informed consent |
| Date of first enrolment | 01/08/2024 |
| Date of final enrolment | 30/12/2026 |
Locations
Countries of recruitment
- United Kingdom
- Scotland
Study participating centre
South Bridge
Edinburgh
EH8 9YL
Scotland
Results and Publications
| Individual participant data (IPD) Intention to share | Yes |
|---|---|
| IPD sharing plan | The datasets generated and/or analysed during this study will be de-identified and may be available for use in future ethically-approved studies, on request. |
Editorial Notes
07/05/2026: Internal review.
21/04/2026: Study's existence confirmed by the South West - Cornwall & Plymouth Research Ethics Committee.
