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.

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 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