Watch this video to learn even more about the AMP RA/SLE Project
Click here to hear from patients with rheumatoid arthritis and lupus and to learn about the importance of the AMP RA/SLE project.
Rheumatoid Arthritis (RA), Systemic Lupus Erythematosus (SLE) & Related Autoimmune Disorders is an initiative of the Accelerating Medicines Partnership (AMP), which is a multi-sector, pre-competitive partnership among government, industry and nonprofit organizations, the goal of which is to harness collective capabilities, scale and resources toward improving current efforts to develop new therapies for complex, heterogeneous diseases. The AMP RA/SLE Program focuses on the molecular analyses of gene expression and signaling in specific subsets of immune cells and resident tissue cells in both RA patients’ synovium and blood and Lupus patients’ kidney biopsy, skin and blood. AMP RA/SLE is using novel technologies to analyze cells on a single cell basis to understand the mechanisms of disease.
In recent years, the ability to target specific immune cells or inflammatory mediators has resulted in the first real advances in the treatment of autoimmune diseases. However, the clinical benefit achieved so far is limited. Despite a significant number of available biotherapies able to reduce RA disease activity in half, a majority of the remaining patients respond poorly to all subsequent drugs and many patients that show initial response to a drug can lose response over time for unknown reasons. In SLE, no effective targeted therapies exist for the most severe forms of the disease including those affecting the central nervous system (CNS) or the kidneys (lupus nephritis). The AMP RA/SLE Program is working collaboratively to define the regulators of aberrant biological pathways and their interactions with tissue cells in order to develop biomarkers which predict pathological processes that lead to organ damage and to identify potential new pathways or targets for drug development and intervention.
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.
Results & Accomplishments
Scientific Publications
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.
Synovial fibroblast expansion in RA is driven by Notch signalling. Nature Reviews Rheumatology. 08 June 2020. https://doi.org/10.1038/s41584-020-0453-x
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
Mixed Effects Association of Single Cells Identifies an Expanded Th1-Skewed Cytotoxic Effector CD4+ T Cell Subset in Rheumatoid Arthritis. Fonseka CY, Rao DA, Teslovich NC, et al. doi: https://doi.org/10.1101/172403
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. doi: https://doi.org/10.1101/351130.
High dimensional analyses of cells dissociated from cryopreserved synovial tissue. Donlin LT, Rao DA, Wei K, et al. doi: https://doi.org/10.1101/284844.
Single cell RNA sequencing to dissect the molecular heterogeneity in lupus nephritis. Der E, Ranabothu S, Suryawanshi H, Akat KM, Clancy R, Morozov P, Kustagi M, Czuppa M, Izmirly P, Belmont HM, Wang T, Jordan N, Bornkamp N, Nwaukoni J, Martinez J, Goilav B, Buyon JP, Tuschl T, Putterman C. JCI Insight. 2017 May 4;2(9). pii: 93009. doi: 10.1172/jci.insight.93009
Data Access
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.
Additional datasets can be accessed through ImmPort, accession: SDY998, SDY999.
Media
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
Partners
Public-Sector Partners:
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Private-Sector Partners:
AbbVie*
Arthritis Foundation*
Bristol-Myers Squibb Company*
GlaxoSmithKline*
Janssen Research and Development, LLC*
Lupus Foundation of America*
Lupus Research Alliance*
Merck & Co., Inc.*
Pfizer Inc*
Rheumatology Research Foundation*
Sanofi*
Takeda Pharmaceuticals International, Inc.*
*Provided financial or in-kind support for this program.
FNIH Contact
Steve Hoffmann, Director, Inflammation and Immunity, shoffmann@fnih.org