NEPHSTROM is a research project which is exploring the use of stem cells to treat diabetic kidney disease. The project is funded by the European Union’s Horizon 2020 programme, and includes partners from Ireland, Germany, the Netherlands, Italy, the UK and Belgium.
The disease: diabetic kidney disease (DKD) is a complication of diabetes. With the rise in diabetes world-wide, the incidence of DKD is increasing rapidly. In 2010, 634,000 EU citizens died from diabetes and its co-morbidities; 10-20% of these died from DKD.
DKD is the leading cause of end-stage renal disease (ESRD) in the EU and US; about 40% of all ESRD patients die within 5 years. DKD is also closely linked to other diseases (co-morbidities), including cardio-vascular disease, and hypertension (high blood pressure), and with poor outcomes for patients with these diseases.
DKD is further linked to other complications of diabetes, including retinopathy (leading to blindness) and neuropathy (leading to chronic pain).
- Diabetes –> DKD –> ESRD –> death
- DKD + CVD/Hypertension –> poor outcomes
The cost: DKD and ESRD represent an enormous burden on healthcare systems and national economies; costs range from $20,000 per year for early-stage DKD to $80,000 per year for patients on dialysis. Overall, some 13.4% of all US Medicare costs are linked to this disease.
No cure: there is currently no effective cure for chronic kidney disease. A range of drugs are used to manage the disease; for a significant number of patients this does not suffice, and they progress to dialysis or (where feasible) kidney transplant.
NEPHSTROM: In NEPHSTROM, we are exploring the use of stem cells to treat DKD, aiming to slow the progression of the disease and to maintain the health and quality of life of the patients.
Why do we think this is a good idea?: In a previous project (the FP7-funded REDDSTAR), we found that stem cell treatment had positive impacts on DKD in a mouse model, and that it benefited several important components, including Glomerular Filtration Rate, urine albumin secretion, glomerulosclerosis and associated inflammation. This provided us with the evidence to progress to this first human trial.
The Cells: we use a unique stem cell product, Orbcel-M, to treat DKD in NEPHSTROM. This product consists of a particular sub-set of all stem cells, which have been isolated from bone marrow using a patented antibody (CD362) technology. The cells are cultured in a bio-reactor, to generate sufficient cells for the treatment, and then injected into the DKD patients.
The Clinical Trial: The core of the project is an early-stage clinical trial, where patients with chronic kidney disease are injected with stem cells; as a result, the project includes clinical trial centres in Ireland (NUI Galway), Italy (Istituto Mario Negri, Bergamo), and the UK (UHBFT, Birmingham and BHSCT, Belfast). The main aim of the trial is to verify the safety of various doses of cells; we also hope to show that important markers of disease are changed (i.e. that the therapy actually works, as well as being safe). We use a double-blinded, randomised study design, to ensure that the results of the trial provide strong scientific evidence for progress to the next stage.
The Patients: The trial will involve 48 patients, all with Type 2 Diabetes, randomised into four groups of 12: one placebo (control) group, and one group each of low, medium and high-dose treatments. Strict inclusion and exclusion criteria are applied, in order (a) to protect the patients and (b) to ensure the best possible quality scientific data is generated. A stringent ethical process is applied, including informed consent, protection of patient confidentiality and privacy data, etc.
The Trial Process: the trial begins by putting in place the regulatory and ethical approvals – without such approvals, no clinical trial can take place. Governance structures to protect the patients and the data are established. Monitoring protocols and processes are put in place, to review safety on a regular basis.
The patients are then recruited in the four centres (Bergamo, Galway, Birmingham and Belfast). They are pre-screened, to ensure they meet the inclusion criteria, and then randomised into four groups (control, low dose, medium dose, high dose). The low-dose patients are treated first; when the safety of the low dose has been established, the medium dose patients are treated next. Following verification of medium-dose safety, the high-dose patients are treated. In parallel, measurements are taken to establish the efficacy of the treatment as a therapy for chronic kidney disease. All patients are followed-up for an extended period, to identify and measure efficacy, and to verify that no longer-term safety issues arise.
What Next?: A successful trial, demonstrating safety and indicating efficacy, would provide the evidence needed to progress to a more advanced trial, with a larger patient population, which would focus on the efficacy of the treatment. It would also enable us to apply for early market approval in several key markets, where regulatory approval for currently-untreatable diseases are fast-tracked.
Future Prospects: There is very strong research that suggests that stem cells can be beneficial in the treatment of other chronic non-communicable diseases, with impact on (among others) inflammation, auto-immunity, oxidative stress, and high blood pressure. A good clinical trial result for a defined stem cell product would provide an excellent precedent for developing treatments for lupus, coronary artery disease, heart failure, asthma and other conditions.