NEPHSTROM Clinical Trial Underway at Four Locations

“We are pleased the NEPHSTROM clinical trial has commenced and that randomized diabetic patients with kidney disease whose previous therapies failed now are receiving ORBCEL-M™ immunotherapy,” said Dr Larry Couture, CEO of Orbsen Therapeutics. “The study may be a breakthrough moment for patients with end-stage renal disease caused by diabetes.”

Orbsen Therapeutics, a biotechnology company focused on the discovery, development and commercialization of first-in-class stromal cell immunotherapies, announced that ORBCEL-M™, a second generation stromal cell immunotherapy, currently is being administered to patients with type 2 diabetes and progressive diabetic kidney disease in a four-site, pan-European Phase I/II clinical trial.

Orbsen’s patented allogeneic ORBCEL-M yields nearly 100 percent pure stromal cells, a significant increase in purity when compared to first generation stromal cell therapies. The NEPHSTROM study aims to prove whether the purer stromal cells in ORBCEL-M will be more effective in the prevention and treatment of diabetic kidney disease. Up to 40 percent of people with diabetes will develop kidney disease. Many will require a kidney transplant or a lifetime of dialysis.

“It’s a privilege to have the first patients enrolled and receiving treatment at the Mario Negri Institute,” said Professor Giuseppe Remuzzi of the Mario Negri Institute in Bergamo, Italy, and the clinical trial’s lead investigator. “The complementary skills and expertise of the four participating European centers provide a critical network demonstrating the clinical feasibility of this innovative therapy and the opportunity for additional coordinated trials in diabetic patients with progressive kidney disease for whom new therapies are urgently needed.”

Professor Timothy O’Brien, founding Director at Orbsen Therapeutics and coordinator of the NEPHSTROM study noted, “In my clinical practice, I see hundreds of patients with diabetic kidney disease who face the unpleasant possibility of dialysis or kidney transplantation. The outcome of this clinical trial may give patients another alternative and new hope.”

ORBCEL-M performed well in pre-clinical models as a therapy for diabetic kidney disease demonstrating significant improvements in kidney function.

“Encouraged by the promising results of the pre-clinical models, we are optimistic taking ORBCEL-M to the next stage to further investigate the immunotherapy as a solution to slow or stop progressive diabetic kidney disease,” said Steve Elliman, Chief Scientific Officer at Orbsen Therapeutics. “On behalf of Orbsen, we are privileged to be engaged with some of the European Union’s leading researchers and institutions through NEPHSTROM.”

NEPHSTROM’s four primary research locations are:

Read the press release here.

Read an interview with NEPHSTROM Coordinator Prof Tim O’Brien, NUI Galway and PI Dr Eric Austin of the NHSBT conducted by the Regenerative Medicine Network.

Five NEPHSTROM partners to participate in GMP November event in Galway

NEPHSTROM partners from NUI Galway, Orbsen Therapeutics, Leiden University Medical Center, Terumo BCT Europe NV and the NHS Blood and Transport will facilitate sessions at the Center for Cell Manufacturing Ireland’s event “GMP Manufacturing, Scale-Up and Challenges of ATMPs”. This 2-day event will take place on November 14 and 15, 2018 at the National University of Ireland Galway.

For more information and to register, please click here.

New NEPHSTROM study published in the CCLM

A new NEPHSTROM study has just been published in the Clinical Chemistry and Laboratory Medicine (CCLM): “Defining reference intervals for a serum growth differentiation factor-15 (GDF-15) assay in a Caucasian population and its potential utility in diabetic kidney disease (DKD)” by Siobhan M. Hamon, Tomás P. Griffin, Md Nahidul Islam, Deirdre Wall, Matthew D. Griffin, and Paula M. O’Shea.

Background: Growth differentiation factor-15 (GDF-15), a stress-responsive cytokine, is a promising biomarker of renal functional decline in diabetic kidney disease (DKD). This study aimed primarily to establish normative data and secondarily to evaluate the potential utility of GDF-15 in DKD using Roche Diagnostics electrochemiluminescence immunoassay (ECLIA) in an Irish Caucasian population.

Methods: Following informed consent, 188 healthy volunteers and 128 participants with diabetes (72 with and 56 without DKD) were recruited to a cross-sectional study. Baseline demographics, anthropometric measurements and laboratory measurements were recorded. Blood for GDF-15 measurement was collected into plain specimen tubes kept at room temperature and processed (centrifugation, separation of serum, freezing at −80 °C) within 1 h of phlebotomy pending batch analyses. Reference intervals were determined using the 2.5th and 97.5th percentiles for serum GDF-15 concentration.

Conclusions: The reference interval for serum GDF-15 in a healthy Irish Caucasian population using Roche Diagnostics ECLIA was established and a preliminary determination of the potential of GDF-15 as a screening test for DKD was made. Further prospective validation with a larger DKD cohort will be required before the cutoff presented here is recommended for clinical use.

Published Online: September 15, 2018 | DOI: https://doi.org/10.1515/cclm-2018-0534

Read the entire NEPHSTROM Publications list here: http://nephstrom.eu/nephstrom-publications/

NEPHSTROM celebrates UK Kidney Week in Harrogate, UK

Prof Paul Cockwell, Consultant Nephrologist of the Queen Elizabeth Hospital Birmingham, UK gave a superb talk about the NEPHSTROM project at the annual conference of the UK Renal Association. The conference was held in Harrogate, England from 19-21 June 2018 during the UK Kidney Week. It was co-organised by the British Renal Society and the Renal Association.
Paul’s talk, “Mesenchymal stromal cells for human kidney disease: NEPHSTROM and beyond” provided the context for using MSCs in combatting disease, including the biological basis for their use, provided an overview of MSCs in relationship to human kidney disease, gave a detailed update of the NEPHSTROM project and concluded with how MSCs could be used as stratified medicine agents in kidney disease.

NEPHSTROM celebrates International Clinical Trials Day with the HRB-TMRN

EU funded projects NEPHSTROM, VISICORTADIPOA-2, and AUTOSTEM coordinated by the Regenerative Medicine Institute (REMEDI) at National University of Ireland, Galway exhibited at a unique outreach activity targeted at primary school students. The event called the START competition was the brainchild of the Health Research Board (Ireland)’s Trials Methodology Research Network (HRB-TMRN) in Galway. In celebration of International Clinical Trials Day and to draw attention to clinical research conducted in Ireland, young people were invited to design, conduct and report on a randomized clinical trial. On May 18, 2018, three of the short-listed schools assembled at the University in Galway to visit interactive exhibitions, talk with researchers, perform mini-experiments, take part in lively science demonstrations and collect their prizes. The winning school was St. Joseph’s National School from Kinvara, County Galway.

Special thanks to Dr Siobhan Gaughan who organized the stand, Georgina Shaw who prepared the stem cell plates and to NUI Galway volunteers Dr Tina Harte, Dr Cathal Ó Flatharta, Dr. Nahidul Islam, Hannah Egan, Niamh Leonard, Dr. Emily Growney Kalaf, Claire Dooley and Dulan Hasantha Jayasooriya who volunteered their time to work with the young people on behalf of the EU funded project, STEM promotion.  The STEMinator cards used at the exhibition were designed by Cúram, NUI Galway. Also thank you to Lauren, Alibhe and Charlotte for creating the stem cell models.

Read more about the START competition here.

Nephstrom study published in Immunology & Cell Biology

A National University of Ireland Galway REMEDI-Cúram-NEPHSTROM- funded study ‘Phenotypic and functional heterogeneity of human intermediate monocytes based on HLA-DR expression’ has been recently published in Immunology & Cell Biology. The body of research by Connaughton EPNaicker SHanley SASlevin SMEykelenboom JKLowndes NFO’Brien TCeredig RGriffin MD, and Dennedy MC was published on 5 March 2018.

 

Abstract

Human blood monocytes are sub-classified as classical, intermediate and non-classical. In this study, it was shown that conventionally-defined human intermediate monocytes (IM) can be divided into two distinct subpopulations with mid- and high-level surface expression of HLA-DR (referred to as DRmid and DRhi IM). These IM subpopulations were phenotypically and functionally characterized in healthy adult blood by flow cytometry, migration assays and lipoprotein uptake assays. Their absolute numbers and proportions were then compared in blood samples from obese and non-obese adults. DRmid and DRhi IM differentially expressed several proteins including CD62L, CD11a, CX3CR1 and CCR2. Overall, the DRmid IM surface profile more closely resembled that of classical monocytes while DRhi IM were more similar to non-classical. However, in contrast to classical monocytes, DRmid IM migrated weakly to CCL2, had reduced intracellular calcium flux following CCR2 ligation and favored adherence to TNF-α-activated endothelium over transmigration. In lipid uptake assays, DRmid IM demonstrated greater internalization of oxidized and acetylated low density lipoprotein than DRhi IM. In obese compared to non-obese adults, proportions and absolute numbers of DRmid , but not DRhi IM, were increased in blood. The results are consistent with phenotypic and functional heterogeneity within the IM subset that may be of specific relevance to lipoprotein scavenging and metabolic health.

doi: 10.1111/imcb.12032. [Epub ahead of print]

NEPHSTROM research published in Frontiers in Immunology

 

The paper ‘Anti-Donor Immune Responses Elicited by Allogeneic Mesenchymal Stem Cells and Their Extracellular Vesicles: Are We Still Learning?’ is based on the work of Dr Paul Lohan, Dr Oliver Treacy, Prof Matthew Griffin, Prof Thomas Ritter and Dr Aideen Ryan of the National University of Ireland Galway. The publication appears in the November 24, 2017, edition of Frontiers in Immunology. This research was funded by NEPHSTROM, amongst other sources. Read the entire manuscript here.

Front. Immunol., 24 November 2017

https://doi.org/10.3389/fimmu.2017.01626

 

‘Chronic Kidney Disease’- a new Nature Reviews Disease Primer by NEPHSTROM researchers

Our partner Prof Dr Hans-Achim Anders of Ludwig-Maximilians-Universitaet Muenchen has coordinated a new publication in Nature Reviews ‘Disease Primers’ on Chronic Kidney Disease  (CKD). Contributing authors are Paola Romagnani, Giuseppe Remuzzi, Richard Glassock,  Adeera Levin, Kitty J. JagerMarcello TonelliZiad MassyChristoph Wanner and  Hans-Joachim Anders.

Abstract:  Chronic kidney disease (CKD) is defined by persistent urine abnormalities, structural abnormalities or impaired excretory renal function suggestive of a loss of functional nephrons. The majority of patients with CKD are at risk of accelerated cardiovascular disease and death. For those who progress to end-stage renal disease, the limited accessibility to renal replacement therapy is a problem in many parts of the world. Risk factors for the development and progression of CKD include low nephron number at birth, nephron loss due to increasing age and acute or chronic kidney injuries caused by toxic exposures or diseases (for example, obesity and type 2 diabetes mellitus). The management of patients with CKD is focused on early detection or prevention, treatment of the underlying cause (if possible) to curb progression and attention to secondary processes that contribute to ongoing nephron loss. Blood pressure control, inhibition of the renin-angiotensin system and disease-specific interventions are the cornerstones of therapy. CKD complications such as anaemia, metabolic acidosis and secondary hyperparathyroidism affect cardiovascular health and quality of life and require diagnosis and treatment.

 

Article number: 17088

doi: 10.1038/nrdp.2017.88

Published online 23 November 2017

NEPHSTROM meets the masses at Ireland’s largest public science forum hosted by NUI Galway

NEPHSTROM researchers at NUI Galway exhibited at the Galway Science and Technology Forum on 26 November 2017. In excess of 20,000 people attended the exhibition day. The NUI Galway regenerative medicine stand was the brainchild of Dr Siobhán Gaughan who works across several EU-funded stem cell projects coordinated at NUI Galway. Researchers Matthew Griffin, Cathal O’ Flatharta, Grace Davey, and Nahidul Islam along with Siobhán Gaughan were on hand to explain the cell research ongoing at the university, the objectives and mission of NEPHSTROM, and to inspire the next generation of stem cell scientists. Several activities were on exhibition.

Microscopes were on hand to display bone marrow-derived MSCs and cells differentiated into fat cells. This display was used as an aid to discuss or explain how we need stem cells in our body to replace dead cells in our body and how these stem cells can differentiate down different pathways to make new fat, bone, skin and muscle.

Anatomical models were exhibited to explain the importance of the three EU-funded clinical trials involving stem cells that currently taking place through the Regenerative Medicine Institute (REMEDI) at NUI Galway:
NEPHSTROM is a project involving a clinical trial which aims to treat diabetic kidney disease using bone marrow-derived stem cells. Complications of diabetes were explained to help contextualise this project and a diabetic foot model with a black toe was also on hand.

ADIPOA-2 is treating osteoarthritis using adipose-derived stromal cells. Cells are isolated from fat tissue procured by liposuction, expanded under GMP (good manufacturing practices) conditions in Centre for Cell Manufacturing in Ireland (CCMI), the cell manufacturing facility at NUI Galway and injected into the knee of people with osteoarthritis. The treatment aims to reduce the pain and inflammation.
VISICORT project aims to treat corneal transplant rejection by using an infusion of human bone marrow-derived stromal cells obtained from healthy bone marrow donors. The cells are expanded in CCMI cell manufacturing facility as a cell product, frozen and shipped to Charite Hospital in Berlin where corneal transplant patients will be treated. The cell therapy used in this trial aims to reduce the risk of rejection of the corneal transplant.

AUTOSTEM is an EU-funded project to develop a robotic clean room platform system for the manufacture of large quantities of cells in bioreactors. These large quantities of therapeutic cells will be required once cell therapy clinical trial results prove successful and a cohort of patients will be line up for treatment worldwide. The AUTOSTEM video ran on a loop for display to the public.

Special thanks to Dr Paul Lohan for tech support with the films and Dr Georgina Shaw for supplying the cells for display. Also to Ning Ge and Yicheng Ding of the iPS cell group at REMEDI led by Prof Sanbing Shen.

For more photos and information about the Galway Science & Technology Festival 2017, please follow us on Twitter @Nephstrom

For more information on the projects mentioned, please see:
NEPHSTROM http://nephstrom.eu/ Led by Prof Tim O’Brien. Infusions of BM-MSCs to treat patients with chronic kidney disease

ADIPOA-2 http://adipoa2.eu/ is led by Prof Frank Barry. Cartilage repair in the knee using stem cells derived from fat.
VISICORThttp://visicort.eu/ is coordinated by Prof Matthew Griffin. Infusions of bone marrow (BM)- derived stem cells to treat people with corneal transplants avoid transplant rejection.
AUTOSTEM http://www.autostem2020.eu/ is coordinated by Prof Mary Murphy. This project is developing a robotic platform and bioreactor which will grow the many cells required to treat future patients. A model bioreactor was available for demonstration.
Galway Advertiser Science Week 2017

European Regulators approve NEPHSTROM Clinical Trial of MSC Therapy for Diabetic Kidney Disease

The stromal cell therapy, ORBCEL-M™, developed as part of NEPHSTROM, a European Union Horizon 2020-funded research project, has been approved to begin testing in a randomised, double-blind, and placebo-controlled European clinical trial to treat diabetic kidney disease.

Orbsen’s ORBCEL-M™, a novel highly purified positively-selected stromal cell therapy for diabetic kidney disease, has demonstrated significant improvements in kidney function in pre-clinical models of diabetic kidney disease, which represents a significant step towards preparing this therapy for clinical application.

The pan-European clinical trial is being led by nephrologist, Professor Giuseppe Remuzzi at the Mario Negri Institute in Bergamo, Italy with clinical trial recruitment sites in Italy, Ireland (HRB Clinical Research Facility, Galway), and the UK (University Hospitals Birmingham NHS Foundation Trust, Birmingham and Belfast Health and Social Care Trust, Belfast). The primary aim of the clinical trial is to establish the safety and efficacy of ORBCEL-M™ and to show that important markers of diabetic kidney disease are improved, thereby indicating the safety and efficiency of ORBCEL-M™.

Diabetic kidney disease is the single leading cause of end-stage renal disease in the industrialised world, accounting for 40% of new cases of end-stage renal disease in the US and EU. The five-year mortality rate is 39% – a rate comparable to many cancers.

Professor Timothy O’Brien, Dean of the College of Medicine, Nursing and Health Sciences at National University of Ireland Galway, and NEPHSTROM coordinator, comments: “This approval is a vital step towards the initiation of clinical development of this promising new approach to the treatment of diabetic kidney disease, and patient enrollment will commence this summer.”

The trial successfully secured voluntary harmonisation procedure (VHP) approval in April 2017. The VHP is designed to simplify clinical trials across multiple European member states by providing a centralised application procedure for clinical trial approval.