Located at NUI Galway, the Centre for Cell Manufacturing Ireland (CCMI) is a custom-built facility designed to expand stem cells for use in human clinical trials. will play crucial roles in the Galway arm of this multicenter clinical trial.
· Project is 4th clinical trial funded by EU testing next-generation stem cell therapy discovered by NUI Galway spin-out, Orbsen Therapeutics
A new €6 million research project (NEPHSTROM) has been funded by the European Union Horizon 2020 programme to evaluate the clinical safety and efficacy of a next-generation cell therapy discovered by Galway-based Orbsen Therapeutics, to combat diabetic kidney disease.
The project will be led by Professor Timothy O’Brien, Director of the Regenerative Medicine Institute (REMEDI) at the National University of Ireland Galway. The four-year project will test the next-generation stromal (stem) cell therapy, called Cyndacel-M, in a four-site clinical trial treating patients in Ireland, Northern Ireland, England and Italy
The ‘stromal’ cells will be purified from healthy donor bone marrow using Orbsen Therapeutics’ patented technology, and expanded into multiple ‘off-the-shelf’ doses for clinical use. By 2016, first-in-man trials will see the stromal cells injected into patients with diabetic kidney disease.
Chronic kidney disease is marked by the gradual destruction of kidney tissue over time and is a major cause of sickness and death in the EU. Inflammation (the body’s immune response where blood flow increases to tissue causing swelling) plays a large part in the majority of kidney disease and this can lead to kidney damage, scar tissue formation (fibrosis) and loss of kidney function. Diabetic kidney disease is a common complication of diabetes mellitusmellitus, and it is estimated that by 2040 it may affect in the region of 200 million people. In most cases of diabetic kidney damage there is no effective medical treatment. The mainstay treatments are drugs, dialysis and kidney transplants, all of which have significant costs and only provide limited protection against adverse outcomes.
The ambitious new research project called NEPHSTROM (Novel Stromal Cell Therapy for Diabetic Kidney Disease) is a collaboration of 11 European partners (www.nephstrom.eu) and builds on pre-clinical research carried out in an existing EU-funded project known as REDDSTAR (www.reddstar.eu). REDDSTAR is also coordinated by Professor Timothy O’Brien and funded by the EU Framework 7 programme.
NUI Galway’s Professor O’Brien comments: “If predictions prove correct, then our healthcare systems are facing a huge task in managing the complications caused by ever-increasing numbers of patients with diabetes mellitus. Chief among such complications will be kidney disease, which has a huge financial cost in terms of current treatments, and takes a massive personal toll on patients. Diabetes is currently the most common cause of end stage kidney disease resulting in the need for dialysis or transplantation. We are confident that by harnessing the most modern approaches in stromal cell therapeutics there may well be a way to halt the progression of diabetic kidney disease using this therapy.”
Spin-out company pioneering next-generation stromal cell therapy
NEPHSTROM will assess next-generation stromal cells that are purified using a patented method developed by Orbsen Theraputics, a spin-out from NUI Galway. Orbsen Chief Scientific Officer, Dr Stephen Elliman - who discovered the Cyndacel technology - explains: “NEPHSTROM is Orbsen’s forth clinical trial funded by the European Commission in the last three years. The data that led to the NEPHSTROM approval was developed via independant testing of Orbsen’s Cyndacel-M in the laboratory of Professor Hans-Joachim Anders at the Ludwigs-Maximillian University in Munich within the REDDSTAR EU network – highlighting the success of that first project.
Cyndacel-M represents a significant advance in terms of stromal cell purification and safety. Whereas competitor technologies are based on a 50-year-old isolation technique, which produces a mixed group of cells for therapeutic use, Orbsen’s Cyndacel technology permits best-in-class purification, which we predict will lead to better safety and efficacy outcomes for patients.”
NEPHSTROM will also develop and validate a new combined manufacturing platform that improves the consistency and reduces the cost of the Cyndacel-M therapeutic to a level that enables its routine clinical use. The project will develop the first “closed-automated” GMP method of stromal cell isolation and expansion that will expand the Cyndacel-M therapy to clinically and commercially relevant numbers. The project will establish an EU network of four GMP cell-production centres, using these technologies, to produce large amounts of therapeutic agent in a consistent manner, following shared protocols. This will be critical to upscaling, delivering the multi-centre trial in NEPHSTROM and meeting the demand for cells in more advanced clinical trials. Cyndacel-M will be manufactured in GMP production centres in Galway, Leiden, Birmingham and Bergamo.
First-in-man clinical trial
In the second year of the project, a clinical trial will take place in Galway, Belfast, Birmingham and Bergamo, among 48 patients. The placebo-controlled trial will see Cyndacel-M injected into the patients’ bloodstream. Results will be measured in terms of improvements in kidney performance as measured by urine and blood samples. If successful, the researchers will see the disease significantly slowed or halted altogether.
One of the world’s most renowned experts in kidney disease, Professor Giuseppe Remuzzi, from the Istituto Di Ricerche Farmacologiche Mario Negri (IRFMN, Bergamo, Italy), will lead the clinical trial across the four centres, set to commence in May 2016. According to Professor Remuzzi: “The core of the NEPHSTROM project is the first-in-man clinical trial with innovative stromal cell therapy in patients with diabetic kidney disease. The clinical experience with stromal cells is still in its infancy, mainly focused on developing novel therapeutic solutions for patients with bone marrow or organ transplantation as well as for those with a small number of autoimmune diseases. Nobody so far has attempted to provide evidence that this cell-based therapy is capable to halt progression of diabetic kidney disease in humans. The NEPHSTROM clinical trial has adopted an approach similar to that pursued to explore the pathophysiology of rare conditions. It is a small but intensively studied clinical trial which will allow determination of the effective dose of Cyndacel-M cells, and how they might function to protect the diabetic kidney.
The complementary skill, expertise and human resources of the four European participating centres contribute to create a strong and critical network to document the clinical feasibility of this innovative therapy, eventually providing the background insights to design future larger clinical trials in diabetic patients with kidney disease.”
NUI Galway’s Centre for Cell Manufacturing Ireland (CCMI) - which is the only licensed cell manufacturing facility in Ireland - the Galway Blood and Tissue Establishment at UHG which is licensed to procure stem cells, and the HRB Galway Clinical Research Facility which has specialised facilities for stem cell clinical trials will play crucial roles in the Galway arm of this multicenter clinical trial.