July 21, 2023
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National Institute of Neurological Disorders and Stroke (NINDS)
This time-sensitive Request for Information (RFI) seeks input from scientists, clinicians, persons with lived experiences (PWLE) in amyotrophic lateral sclerosis (ALS), and the broader community on the most promising opportunities for biomarker research in ALS, as well as recommendations for the collection of clinical biospecimens to facilitate such research.
Background:
ALS is a rapidly progressive, ultimately fatal, neurodegenerative disease with approximately 32,000 cases in the United States (U.S.) or a prevalence rate of 9.9 per 100,000 U.S. population (see National ALS Registry Dashboard). The disease affects both upper and lower motor neurons, causing weakness and wasting of most skeletal muscles, including the diaphragm. In 35-45% of cases, non-motor neurons in the frontal and temporal regions of the brain are also affected, giving rise to a distinctive type of dementia referred to as frontotemporal dementia. There is considerable variability in the phenotypic presentation and progression of ALS, posing significant challenges for early diagnosis as well as the design and analysis of clinical trials in ALS.
A biomarker is a defined characteristic that is measured as an indicator of normal biological or pathogenic processes as well as responses to an exposure or therapeutic intervention. The FDA published “The Biomarkers, EndpointS and other Tools (BEST) glossary” to define different biomarker categories and their corresponding contexts of use in drug development, all of which have high relevance for ALS. Although biomarker discovery is an active research area across many neurological disorders, including ALS, only few biomarkers are sufficiently validated for routine use in clinical trials to advance therapeutic development or clinical practice to help guide clinical care decisions. A need for establishing diagnostic biomarkers to detect ALS in its earliest stages as well as digital monitoring biomarkers to track disease progression accurately and continuously in a home-setting was highlighted in the 2023 NIH Priorities for ALS Research.
Section 3 of the Accelerating Access to Critical Therapies for ALS Act (ACT for ALS; P.L. 117-79) established a Public-Private Partnership for neurodegenerative diseases between the NIH, the FDA, and one or more eligible entities, for the purpose of advancing the understanding of neurodegenerative diseases and fostering the development of treatments for ALS and other rare neurodegenerative diseases. Future activities conducted by this partnership may include prospective biomarker studies and the establishment of a repository of clinical biospecimens that are integrated with individual-level clinical data to facilitate biomarker research.
Information requested:
This RFI invites comments, ideas, and information related to current gaps and opportunities in biomarker research in ALS, as well as recommendations for the collection of clinical biospecimens to facilitate such research. The input sought by NINDS includes, but is not limited to, comments addressing any or all of the following areas of interest:
ALS Biomarker Discovery and Validation:
- Most promising technologies and analytical approaches to advance biomarker research in ALS
- Experiences in conducting biomarker discovery studies using multiple platforms in independent laboratories on the same biospecimens, including challenges encountered and approaches used to overcome these challenges
- Most promising biomarker(s) for ALS that warrant rigorous validation, including:
- Rationale for why the biomarker(s) is (are) promising and the recommended context(s) of use
- Gaps in evidence and/or challenges with measuring or implementing the biomarker(s) for use in clinical trials or clinical care
- Issues in the performance characteristics of the detection method (how the biomarker is measured) in terms of reproducibility and accuracy in measuring the biomarker(s)
- For (a) biomarker(s) used as part of New Drug Application (IND)-enabling studies or in clinical trials, strengths or challenges in the measurement and interpretation of the biomarker(s) to facilitate the next step in the therapeutic development pathway
Clinical Biospecimens:
- Most critical types of clinical biospecimens to advance ALS biomarker research, including recommended methodology and frequency of collection as well as standardization of sample preparation
- Recommended types of individual-level associated clinical data (i.e., clinical features and their recommended assessments)
How to Submit a Response
To assure full consideration, your responses must be received by September 8, 2023. Responses must be submitted via email to [email protected] with “ALS biomarkers” in the subject line.
Responses are voluntary and may be submitted anonymously. Responders 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. Submitted information will not be considered confidential. Responses may be shared publicly on an NIH website. Please do not include any personally identifiable or other information that you do not wish to make public. No proprietary, classified, confidential, or sensitive information should 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 NIH will not make any awards based on responses to this RFI or pay for the preparation of any information submitted or for the Government’s use of such information.
Amelie Gubitz, PhD
National Institute of Neurological Disorders and Stroke/Division of Neuroscience
Email: [email protected]
and Human Services (HHS)
