Request for Information (RFI) on the Future Directions of Lupus Research


Notice Number:

NOT-AR-15-007

Key Dates

Release Date: December 17, 2014

Response Date: January 30, 2015

Related Announcements

NOT-AR-15-018
NOT-AR-15-009

Issued by

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Purpose

The NIAMS is leading an effort to evaluate progress on The Future Directions of Lupus Research (lupus plan), which was released in 2007, and to develop a coordinated action plan for future lupus research at the request of the Congressional Lupus Caucus. To help inform this process, we welcome comments from the public including significant accomplishments since the release of the lupus plan, important opportunities in lupus research, and suggestions for updating the Broad Goals and Priorities elaborated in the 2007 lupus plan.

Background

NIH’s mission is to seek fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to enhance health, lengthen life, and reduce illness and disability. The National Institute of Arthritis and Musculoskeletal and Skin Diseases, and a number of other Institutes and Centers support lupus-related research at the NIH, and the NIAMS facilitates collaboration among the NIH Institutes, other Federal agencies, and voluntary and professional organizations with shared interests in lupus.

Systemic lupus erythematosus (SLE, or lupus) is a complex, heterogeneous, multisystem autoimmune disease that predominantly affects women of childbearing age. Lupus severity ranges on a spectrum from mild to severe, and in its most severe forms lupus can cause significant morbidity and mortality. No effective targeted therapies exist for the most severe forms of the disease, including lupus nephritis, and lupus affecting the central nervous system. A major challenge remains to find new targeted therapies that can achieve a high degree of disease activity reduction (i.e., remission) or disease cure, and therapies that have fewer immunosuppressive side effects.

The fiscal year 2005 House Appropriations Committee Report Language directed the NIH to develop a plan to guide the nation's investment in lupus research. To identify the opportunities, priorities and needs in lupus research that should be considered for inclusion in the research plan, a workshop consisting of scientific experts in the field of lupus was organized for two days of presentations and discussion. The highlights of their conclusions were reported, in The Future Directions of Lupus Research released in 2007.

Through the individual and collaborative activities of researchers, clinicians, and stakeholders in the lupus community, there have been significant advances in understanding of disease mechanisms, evolution of new partnerships, and advances in drug discovery and development that have fostered candidate therapeutics, FDA approval of a new therapeutic, and improvements in the care and quality of life for affected individuals. At this time, there are new challenges and opportunities that would benefit from an assessment of progress and current needs, as requested by the Congressional Lupus Caucus.

Information Requested

Through this Request for Information (RFI), NIAMS invites researchers in academia and industry, health care professionals, patient advocates, representatives of health advocacy organizations, members of scientific or professional organizations, and other interested members of the public to provide comments from their perspective on progress made toward the Broad Goals and Priorities in the 2007 lupus plan, and on current opportunities in lupus research.

We also welcome input that includes, but is not limited to, the following topics:

  • The most significant advances/publications since 2007 in your area of interest/expertise.
  • The most important scientific opportunities in lupus research.
  • Identification of areas that are ready for progress in the short term.
  • Description of gaps to be addressed in order to advance lupus research.
  • Topics to add or remove from the Broad Goals and Priorities elaborated in the 2007 plan (listed below), so that the current state of the science is reflected.

Appendix A: The Future Directions of Lupus Research

Broad Goals and Priorities
Lay the Foundation for Lupus Prevention

Lupus prevention may become an attainable goal in the next decade. To achieve this goal it will be critical to advance and coordinate research efforts to:

  • Identify populations at risk
  • Identify risk of disease
  • Family studies
  • Genetics
  • Evaluation of the best options for prevention
Identify Triggers of Disease

The interplay between genes and environmental factors needs to be dissected and defined in individual patients and in patient subsets. Critical to this goal will be to define triggers:

  • Endogenous: genes, hormones
  • Exogenous: infectious agents, chemical exposures, biopsychosocial factors
Define Target Organ Damage Mechanisms

The goal is to prevent progression of target organ damage. It will be critical to acquire technologies for the assessment of multiple and overlapping mechanisms of disease occurring over time that cause irreversible damage. These include identification of:

  • Inherent target organ susceptibility factors
  • Mechanisms of injury: immune, inflammatory, vascular
  • Mechanisms of progression: repair failure, abnormal clearance, persistence of triggering agent
  • Mechanisms of recovery
  • Role of local cells
  • Measurement of injury: non-invasive rapid assays
Understand Autoantibodies

The role of autoantibodies in disease and their use as biomarkers needs to be fully understood. Research priorities and opportunities exist on:

  • Defining the genes that regulate tolerance to self and production of autoantibodies
  • Role in pathogenesis via traditional and functional mechanisms
  • Interaction with target organ targets
  • Initiation/induction of tissue damage
  • Targeting their effector function for therapeutic purposes
  • Role and use as biomarkers
Expand Biopsychosocial Research

The goal is to increase our understanding of behavioral, psychological and societal factors that affect the course and the long term outcomes in the disease. Modifiable factors could be identified through research on:

  • Epidemiology
  • Impediments to access of care and maintaining status quo of therapies
  • Quality of life
  • Self-report vs. physician report
  • Interactions with institutions, government, etc., and their effect on long-term outcomes
  • Interaction with other psychiatric disease
  • Mind/body interactions
  • Cognitive affliction
  • Coping styles
  • Support groups
  • Family
  • Transition from pediatric to adult
  • Disparities
  • Poverty, race/ethnicity
  • Origin and mechanisms of fatigue
Discover and Validate Biomarkers

The goal during the next few years will be to use modern approaches to discovery and validation of existing biomarkers for lupus diagnosis, prognosis and evaluation of therapies. Promising biomarkers are likely to emerge from research on:

  • Genetics
  • Polymorphisms and gene products evaluated by novel technologies such as microarrays and proteomics
  • Validation studies in well characterized patient cohorts
  • Analysis of potential use of selected biomarkers and their combinations in clinical subsets
Move Forward Treatment and Therapy

New treatments for lupus are being tested by the private sectors. The goal of the NIH and academic research will be to ensure a continuous supply of new targets for intervention and adequate trial methodologies. Research likely to contribute to this goal will be focused on:

  • Identification of targets for non-immunosuppressive therapies
  • Target organ repair
  • Collateral damage musculoskeletal, cardiovascular, chronic fatigue, mild myalgia
  • Prevention of collateral damage
  • Treatment of symptoms (e.g., cognitive rehabilitation, control of fatigue)
Resources and Infrastructure

To achieve the goals of this plan, critical resources will be needed, and they will have to be implemented in creative and dynamic ways to ensure rapid progress. Implementation will require careful attention to achieving an adequate balance between investigator-initiated research and network/collaborative large projects. The following is a list of some of those resources. Their acquisition and maintenance will require collaborative approaches by the funding organization, the academic centers and the private sector.

Patient Collections

Issues affecting the collection and sharing of patient cohorts that will have to be addressed include:

  • Accessibility
  • Control populations
  • Registry maintenance facilitation
  • Specimen collection with clinical trials
  • More patients for intervention
Partnerships

A collaborative environment that facilitates sharing of data, specimens and information will enhance research and research careers in lupus. For example, immunologists and rheumatologists should seek direction from other areas like reproductive medicine, neurophysiology, cell biology, and hematology. Some principles that may guide their development include:

  • Free exchange between academic investigators and industry
  • Free exchange between investigators
  • Educate institutions on collaborative efforts
  • Participation of patient groups
Training
  • Education physicians for new therapies
  • New investigators

The collected comments will be reviewed and considered as we evaluate progress and develop updated Broad Goals and Priorities in response to the request from the Congressional Lupus Caucus.

How to Submit a Response

Responses to this RFI must be submitted electronically by email to the following address: [email protected]. Please indicate in your response the topic(s) you are addressing, and which of the Broad Goals and Priorities it is related to. Responses will be accepted until January 30, 2015.

Responses to this RFI are voluntary. Please do not include any personally identifiable or other information that you do not wish to make public. Proprietary, classified, confidential, or sensitive information should not be included in your response.

This request is for information and planning purposes only and should not be construed as a solicitation or as an obligation on the part of the United States Government. The NIAMS or the NIH will not make any awards based on responses to this RFI, nor will the NIAMS or the NIH otherwise pay for the preparation of any information submitted or for the Government's use of such information.

The NIAMS will use the information submitted in response to this RFI at its discretion and will not provide comments to any responder's submission. Respondents are advised that the Government is under no obligation to acknowledge receipt of the information received or provide feedback to respondents with respect to any information submitted. The Government reserves the right to use any non-proprietary technical information in any resultant solicitation(s).

Inquiries

Please direct all inquiries to:

Stephanie Burrows, Ph.D.
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-496-8271
Email: [email protected]

Katy Marron, Ph.D.
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-594-5032
Email: [email protected]