Thursday, April 25, 2024 4/25/2024

A Phase II Controlled Trial of Allogeneic Mesenchymal Stem Cells for the Treatment of Refractory Lupus

Award Number: U01AI125159
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By Issue Date FY or Funding FY:

View Award Abstract

PROJECT SUMMARY/ABSTRACT Determining the clinical effectiveness of mesenchymal stem cells (MSCs) and their mechanism of action in treating refractory lupus is of significant importance. We and others have reported reproducible improvement in murine models of lupus following allogeneic MSC infusions from healthy mice or humans. Infusion of MSCs, derived from bone marrow or umbilical cords, in more than 100 treatment-refractory lupus patients has resulted in positive clinical benefit in 65-75% of those treated. However, a placebo-controlled trial of MSCs in lupus has not been performed to show definitively that MSCs are more effective than standard of care. One clear result from multiple trials of MSCs to date is that they can be given safely with almost no serious adverse events. The preclinical data, the uncontrolled trials and the safety profile create a mandate for a controlled trial to test the efficacy of MSCs as a therapeutic for lupus. Critical to this trial are mechanistic studies to define how MSCs impact disease. Prior studies in lupus and rheumatoid arthritis reported increased circulating Treg cells, decreased Th17 cells, decreased TFH cells and fewer activated B and plasma cells in patients after MSC infusion. The mechanism by which these cellular effects occur is unknown. We have found that lupus patients have decreased circulating levels of glycoprotein A repetitions predominant (GARP)/TGF¿ complexes. MSCs express GARP, and GARP is a major determinant of TGF¿ bioactivity and also has important enhancing effects on Treg number and function. We hypothesize that allogeneic MSC infusion, plus standard of care, will prove significantly more effective in treating lupus patients with active disease than standard of care alone. We further hypothesize that effects of MSCs in lupus occur via modulation of regulatory and pathogenic T and B cells through upregulation of GARP expression, resulting in enhanced TGF¿ bioactivity and increased Treg numbers and activity. To test these hypotheses, our specific aims are to: 1. Determine the safety and efficacy of mesenchymal stem cell therapy in a two-dose escalation double- blind placebo-controlled multi-center trial as a treatment for lupus patients with moderate to severe disease activity unresponsive to standard of care therapy compared to ongoing standard of care. 2. Define mechanistically how MSCs modulate regulatory and pathogenic T and B cells in lupus patients and the role of GARP-mediated TFG¿ bioactivity in this process. The proposed trial will be performed in six academic centers that are all skilled, successful and experienced in performing lupus trials. If we confirm that MSC therapy is as effective as reported, then MSC infusions may become an alternative therapy for lupus. The detailed mechanistic analysis will provide novel insight into the complex cellular matrix in lupus and the impact MSCs have on these cellular interactions. There is a defined FDA pathway for licensing cellular therapies allowing this therapy, if effective, to be translated to the clinic.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2023 ( Subtotal = $464,370 )
2023	2023	MEDICAL UNIVERSITY OF SOUTH CAROLINA THE	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Allergy and Infectious Diseases Research	002	6	8/15/2023	EXTENSION WITH OR WITHOUT FUNDS	$464,370
2023	2022	MEDICAL UNIVERSITY OF SOUTH CAROLINA THE	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Allergy and Infectious Diseases Research	000	5	11/10/2022	NON-COMPETING CONTINUATION	$0
2023	2022	MEDICAL UNIVERSITY OF SOUTH CAROLINA THE	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Allergy and Infectious Diseases Research	001	5	8/3/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $464,370

Issue Date FY: 2022 ( Subtotal = $707,818 )
2022	2022	MEDICAL UNIVERSITY OF SOUTH CAROLINA THE	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Allergy and Infectious Diseases Research	001	5	4/4/2022	NON-COMPETING CONTINUATION	$707,818
2022	2021	MEDICAL UNIVERSITY OF SOUTH CAROLINA THE	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Allergy and Infectious Diseases Research	000	4	10/29/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $707,818

Issue Date FY: 2021 ( Subtotal = $707,818 )
2021	2021	MEDICAL UNIVERSITY OF SOUTH CAROLINA THE	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Allergy and Infectious Diseases Research	001	4	2/19/2021	NON-COMPETING CONTINUATION	$707,818
2021	2020	MEDICAL UNIVERSITY OF SOUTH CAROLINA THE	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Allergy and Infectious Diseases Research	000	3	12/14/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $707,818

Issue Date FY: 2020 ( Subtotal = $707,818 )
2020	2020	MEDICAL UNIVERSITY OF SOUTH CAROLINA	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Allergy and Infectious Diseases Research	000	3	2/12/2020	NON-COMPETING CONTINUATION	$707,818
														Subtotal = $707,818

Issue Date FY: 2019 ( Subtotal = $707,818 )
2019	2019	MEDICAL UNIVERSITY OF SOUTH CAROLINA	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Allergy and Infectious Diseases Research	000	2	2/11/2019	NON-COMPETING CONTINUATION	$707,818
2019	2019	MEDICAL UNIVERSITY OF SOUTH CAROLINA	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Allergy and Infectious Diseases Research	001	2	9/13/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $707,818

Issue Date FY: 2018 ( Subtotal = $720,193 )
2018	2018	MEDICAL UNIVERSITY OF SOUTH CAROLINA	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Allergy and Infectious Diseases Research	000	1	3/19/2018	NEW	$720,193
														Subtotal = $720,193

Grand Total All Awards = $4,015,835

Top

All Categories

About

Search

Reports

Data Submission

Award Information

A Phase II Controlled Trial of Allogeneic Mesenchymal Stem Cells for the Treatment of Refractory Lupus

Award Number: U01AI125159

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer