Accelerating Medicines Partnership – Rheumatoid Arthritis, Systemic Lupus Erythematosus
Enhancing the biological understanding of complex autoimmune disorders to enable better treatments for patients
The FNIH’s Accelerating Medicines Partnership (AMP) program includes an initiative focused on Rheumatoid Arthritis (RA), Systemic Lupus Erythematosus (SLE) & Related Autoimmune Disorders. AMP is a multi-sector, pre-competitive partnership among government, industry and nonprofit organizations that aims to harness collective capabilities, scale and resources to improve current efforts to develop new therapies for complex, heterogeneous diseases. The AMP RA/SLE Program focuses on molecular analyses of gene expression and signaling in specific subsets of immune cells and resident tissue cells, in RA patients’ synovium and blood and in lupus patients’ kidney biopsy, skin and blood. AMP RA/SLE uses novel technologies to molecularly deconstruct and analyze these highly refined relevant cell subsets or single cells, in order to understand the mechanisms of disease.
In recent years, treatment of autoimmune diseases has benefited from the ability of therapies to target specific immune cells and inflammatory mediators. However, the clinical benefits achieved so far have been limited. For example, despite an increase in the number of available biotherapies that reduce RA disease activity, many patients respond poorly to all current therapeutics, and many patients who initially respond to a drug experience diminished responses over time, for unknown reasons. Moreover, no effective therapies exist for the most severe forms of SLE, including those affecting the central nervous system (CNS) or the kidneys (e.g., lupus nephritis). The collaborative AMP RA/SLE Program is working to transform the approach to defining the pathogenesis of autoimmune diseases, improve patient enrichment strategies to ensure the best use of existing therapies and enable the identification of potential new pathways or targets for RA/SLE drug development and intervention.
Click here to watch a video about the AMP RA/Lupus program from a patient perspective.
- National Institute of Allergy and Infectious Diseases (NIAID)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
- Arthritis Foundation*
- Bristol-Myers Squibb Company*
- Janssen Research and Development, LLC*
- Lupus Foundation of America*
- Lupus Research Alliance*
- Merck & Co., Inc.*
- Pfizer Inc*
- Rheumatology Research Foundation*
- Takeda Pharmaceuticals International, Inc.*
*Provided financial or in-kind support for this program.
Results & Accomplishments
IFN-γ and TNF-α drive a CXCL10+ CCL2+ macrophage phenotype expanded in severe COVID-19 lungs and inflammatory diseases with tissue inflammation. Fan Zhang, Joseph R. Mears, Lorien Shakib, Jessica I. Beynor, Sara Shanaj, Ilya Korsunsky, Aparna Nathan, Accelerating Medicines Partnership Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Consortium, Laura T. Donlin6, and Soumya Raychaudhuri. Genome Med. 2021 Apr 20;13(1):64. doi: 10.1186/s13073-021-00881-3. https://doi.org/10.1186/s13073-021-00881-3
- AMP RA/SLE has led to nineteen peer-reviewed scientific journal articles.
- Data from Phase 1 of the research plan was made publicly available on November 1, 2017. Genotype and Phenotype data are available upon authorized request through dbGaP, accession phs001457. v1. p1. Read more
- Additional datasets can be accessed through ImmPort, accession: SDY998, SDY999. Read more
- Learn about the AMP projects focused on Alzheimer’s disease, type 2 diabetes and Parkinson's disease.
- Read a program overview on the NIAMS website here.
- Prime time in rheumatoid arthritis. Gravallese E. and Robinson, W. N Engl J Med. 2020 Jul 16;383(3):278-279, doi: 10.1056/NEJMe2018218
- RNA identification of prime cells predicting rheumatoid arthritis flares. Orange DE., Yao, V., Sawicka, K., et al. N Engl J Med 2020; 383:218-228, doi: 10.1056/NEJMoa2004114
- Integrated urine proteomics and renal single-cell genomics identify an IFN-γ response gradient in lupus nephritis. Fava A, et al. JCI insight. 18 June 2020. https://doi.org/10.1172/jci.insight.138345.
- Notch signaling drives synovial fibroblast identity and arthritis pathology. Wei K, Korsunsky I, et al. Nature (2020). https://doi.org/10.1038/s41586-020-2222-z
- The Accelerating Medicines Partnership – Organizational Structure and Preliminary Data from the Phase 1 Studies of Lupus Nephritis. Hoover P, Der E, Berthier CC, et al. Arthritis Care Res (Hoboken). 2020 Feb;72(2):233-242. doi: 10.1002/acr.24066. Epub 2020 Jan 13
- PD-1hiCXCR5– T peripheral helper cells promote B cell responses in lupus via MAF and IL-21. Bocharnikov AV, Keegan J, Wacleche VS, et al. JCI Insight. 2019;4(20):e130062. https://doi.org/10.1172/jci.insight.130062.
- The Immune cell landscape in kidney of lupus nephritis. Arazi A, Rao DA, Berthier CC. Nature Immunology volume 20, pages902–914(2019). https://doi.org/10.1038/s41590-019-0398-x
- Defining Inflammatory Cell States in Rheumatoid Arthritis Joint Synovial Tissues by Integrating Single-cell Transcriptomics and Mass Cytometry. Zhang F, Wei K, Slowikowski K, et al. Nat Immunol. 2019 Jul; 20(7): 928–942. doi: 10.1038/s41590-019-0378-1
- Methods for high-dimensional analysis of cells dissociated from cryopreserved synovial tissue. Donlin LT, Rao DA, Wei K, et al. Arthritis Res Ther. 2018; 20: 139. doi: 10.1186/s13075-018-1631-y
- Single cell RNA sequencing to dissect the molecular heterogeneity in lupus nephritis. Der E, Ranabothu S, Suryawanshi H, et al. JCI Insight. 2017 May 4;2(9). pii: 93009. doi: 10.1172/jci.insight.93009
- AMP RA/SLE Project Plan
- Nature Reviews Drug Discovery (February 27, 2019): Massive NIH-industry project opens portals to target validation.
- FNIH Web Announcement (December 14, 2018): Accelerating Medicines Partnership (AMP) Extends the RA and Lupus Research Program to Maximize the Benefits of Emerging Technologies to Advance New Therapies
- NIH Press Release (February 21, 2018): NIH Program to Accelerate Therapies for Arthritis, Lupus Releases First Datasets
- The Rheumatologist (September 26, 2017): AMP RA/Lupus Network Shares Its Progress
- White House Statement (February 4, 2014): Statement by the President on the Accelerated Medicine Partnership
- NIH Press Release (February 4, 2014): NIH, industry and non-profits join forces to speed validation of disease targets