The CZI Neurodegeneration Challenge Network has three key goals:
(1) To make fundamental advances toward understanding neurodegeneration;
(2) To bring new ideas and talent to the field of neurodegeneration; and
(3) To encourage and experiment with a new interdisciplinary, collaborative, and open science research model involving scientists, clinicians, and engineers.
CZI Neurodegeneration Challenge Network
The Neurodegeneration Challenge Network model is built on the vision that progress in solving neurodegenerative diseases will come from bringing new people into the neurodegeneration field from diverse disciplines and expertise; building interdisciplinary collaborations; empowering the broader scientific community with robust tools and platforms, and creating a culture of open science. Scientifically, we aspire to motivate the collective field to shift the approach to neurodegenerative diseases to a framework, where these diseases—currently addressed largely as distinct diseases and problems—are considered more holistically as a class of disorders with common features, mechanisms, and solutions. The Patient-Partnered Collaborations for Rare Neurodegenerative Disease RFA extends on this vision by expanding the scope of diseases and biological problems covered within NDCN, and widens the circle of experts and stakeholders to include patient organizations as collaborators, building on learnings from CZI’s Rare as One Network and CZI’s efforts in patient-directed research.
In the three years since launching the Neurodegeneration Challenge Network (NDCN) in 2018, the Network has grown to a thriving collaborative network that includes 56 teams, 108 labs and over 500 affiliated students, postdocs, and staff scientists. We are now pleased to invite applications to join the Neurodegeneration Challenge Network through a new Request for Applications (RFA) and grant program, the Patient-Partnered Collaborations for Rare Neurodegenerative Disease.
Building on the previous NDCN grant programs, including the NDCN Ben Barres Early Career Acceleration Award, the Collaborative Science Awards, and the Collaborative Pairs Pilot Projects, this RFA will also prioritize bringing new investigators and early-career scientists into the field. There will be an additional emphasis on recruiting scientists from fields outside the core of neurodegeneration and rare disease, and will target work that addresses the biology of rare neurodegenerative diseases in a novel, innovative, interdisciplinary, and disease cross-cutting way. To learn more, read about the Neurodegeneration Challenge Network, Rare As One Cycle One grantee announcement and Cycle Two announcement, and watch the NDCN video.
Patient-centered and foundational science-focused, this RFA aims to expand the understanding of the pathophysiology and mechanistic underpinnings of rare neurodegenerative disease and to channel the focus of research efforts towards issues and questions that are critically relevant to the patient experience. This RFA will not focus on therapeutic or clinical development. However, in centering the work on foundational science and closing critical knowledge gaps, these projects will build a strong foundation for translational efforts. We also see tremendous opportunity for the study of these rare neurodegenerative conditions to inform our understanding of neurodegenerative diseases more broadly, including common diseases.
The focus of the RFA is on rare neurodegenerative diseases and neurological diseases with neurodegenerative features. Examples of diseases that would fall within scope include, but are not limited to, lysosomal storage disorders, neuropathies, spastic paraplegias, ataxias, leukodystrophies, rare metabolic and autoimmune disorders leading to neurodegenerative disease, myopathies and muscular dystrophies, encephalophathies, and rare epilepsies in cases where there are degenerative features. Neurodevelopmental and neuropsychiatric disorders that are not considered neurodegenerative by consensus clinical criteria (autism, for instance) are not within scope for this RFA.
A key aim of this RFA is to encourage research in rare neurodegenerative diseases where research has been limited; rare disease areas where there are currently robust, mature research efforts and active research communities and/or significant funding by federal and philanthropic initiatives will be of lower priority. Examples of rare neurodegenerative disease areas which we consider to be mature fields of research include, but are not limited to, ALS, Huntington’s Disease, Frontotemporal Dementia, Spinal Muscular Atrophy. We are open to consideration of proposals that address rare sub-populations of patients that are understudied and of unique scientific value. Applicants will be required to provide an overview of the clinical and biological features of the disease that is the subject of the application and a statement of the evidence in support of the disease being neurodegenerative and a case for why the disease area is understudied.
We particularly encourage project proposals that address health disparities or focus on rare diseases that predominantly affect underrepresented populations, particularly ancestries that are underrepresented in biomedical research.
Consistent with NDCN’s focus on discovery science, this RFA is open to proposals for discovery science projects that are exploring foundational understanding of causes, progression, or mechanisms of rare neurodegenerative and neurological disorders. Proposals should center on a research question and clear research strategy.
Examples of the types of projects that would meet these criteria could include, but are not limited to:
- Projects that aim to address critical knowledge gaps about disease causes, clinical progression or mechanisms of action
- Projects that bridge natural history studies and mechanistic investigations
- Development of new models to support better understanding of disease mechanism
- Preclinical mechanistic work in support of therapeutic development; for instance, perturbation studies on a candidate mechanism in a disease model, proof of concept for reversal, disease mitigation in a disease model. The emphasis of this RFA will be on mechanistic work that provides insight into disease biology rather than therapeutic drug screens.
- Collaborative cross-disease research (for instance, exploring common mechanisms that affect more than one disease)
- Data-centered approaches that generate and/or analyze biological and clinical data sets, for the purpose of developing biomarkers, insights into disease mechanisms
- Longitudinal history studies that track disease development and provide insight into critical periods of disease progression and potential critical therapeutic windows
- Projects that provide critical insights into comorbidities, for instance, neuroimmune or metabolic influences on neurodegeneration.
Areas that are out of scope of this RFA:
- Clinical trials or pre-clinical research aimed primarily at clinical trial readiness (e.g., toxicology studies)
- Tool or resource development that is not tied to a specific research plan or agenda. This could include the development of research technologies, models (cell lines, animal models) or other types of infrastructure development (e.g., registries). We view the development of hiqh-quality, robust research tools as critical for accelerating science; however, for this RFA, such tool and resource development efforts should be clearly connected to specific research questions.
Collaboration is a central feature of this RFA and grant program. Applications will each have two lead Principal Investigators (PIs): one representing the research team and the other representing the patient organization. Teams should be made up of a minimum of two investigators with a maximum of five investigators, including the patient organization leader. Applications should be co-written by the researchers and the patient-organization representative. Applications will be accepted from newly formed collaborative teams who have not worked together previously or established researcher-patient organization collaborative teams who are proposing new research directions. We will prioritize teams that are taking a fresh, innovative approach to tackling these challenging diseases.
The criteria below for team composition are intended to allow for flexibility in team composition, while ensuring that there is strong co-ownership of the collaboration between the research and patient-advocate partners. If applicants have a question about their team’s composition and eligibility, please contact email@example.com.
To allow tight collaboration and coordination of research efforts, this RFA is focused on small group collaborations. Teams should be made up of a minimum of two Principal Investigators (PIs) to a maximum of five PIs. All PIs are expected to actively contribute to the project and engage in program and network level activities, such as investigator meetings and workshops where relevant. Below we describe the roles of the PIs.
- Coordinating research PI / lead-research PI: Teams should designate a coordinating PI, the scientific lead of the research project, who coordinates the research team. The lead-research PI will also be the Coordinating PI of the grant to submit the application on behalf of the collaborating team. The Coordinating PI will act as the administrative contact between CZI and all other co-PIs on the grant. The Coordinating PI must submit the application on behalf of all PIs (including the Lead Patient Organization PI, see below) and ensure that the collaborative team has the necessary skills to deliver on the aims of the project. The Coordinating PI must be affiliated with the academic/research institution submitting the application, and grant funds will be awarded to that institution, which will take responsibility for distributing funds to all other research institutions (patient funds will be awarded directly to the patient organization). Note that institutions outside the U.S. may not subcontract to U.S. institutions, so please be mindful when selecting the Coordinating PI/institution.
- Lead Patient Organization PI: Will represent the patient organization. The research team should coordinate with one patient-led rare disease organization. If the project requires collaboration with more than one patient-led rare disease organization, please reach out to firstname.lastname@example.org to discuss.
- Up to three additional co-PIs:
- Teams may designate up to three additional research co-PIs from one or more research institutions. Co-PIs may be from the same or different research institutions as the Coordinating PI. The strongest applications will incorporate interdisciplinary expertise and perspectives. Teams may also include additional collaborators and contractors but only 3 individuals can be listed as research co-PIs.
- Each team must include at least one clinician with expertise relevant to the application and experience working with patients in this disease area. It is allowable for the clinician to either be located at a research institution or be designated as the Lead Patient Organization PI.
Diversity, Equity, & Inclusion
- We believe that the strongest teams incorporate a wide range of voices. Those underrepresented in science and technology are strongly encouraged to apply. This includes but is not limited to women, those with disabilities, underrepresented racial and ethnic groups, LGBTQ individuals, and organizations representing disease areas that disproportionately impact underrepresented or underserved communities.
- Researchers and patient organizations from the Global South and low-to-middle income countries, in particular those with populations that have historically been underrepresented in biomedical research, are strongly encouraged to apply and to be included as members of international collaborative networks. International collaborations between investigators and rare disease organizations in the Global North and South that leverage regional and technological expertise and strengths are encouraged. It is the expectation that international collaborations will follow guidelines for conducting research in an equitable and mutually beneficial manner.
Collaboration and Open Science
All projects will be evaluated based on their potential for scientific output (productivity), tool and resource dissemination (reach), inclusion of representative donors and communities, and collaboration among the team. We are looking for investigators and groups who will enthusiastically contribute to and benefit from a collaborative, dynamic, and interdisciplinary approach. For examples of evidence of productivity, reach, and collaboration, please see the CZI statement of values.
- In addition to providing funding, CZI functions as a scientific partner to grantees to help build open and accessible tools and datasets that serve as references for healthy and disease states. Investigators will have the opportunity to learn from, collaborate with, and interact with the community of investigators and groups across all Networks, as well as with CZI computational biologists and software engineers.
- CZI supports collaboration. All PIs listed on the application are expected to participate in project meetings, reports, and other events. Networks should be genuine collaborative projects with responsibility and participation distributed across participating research groups and organizations. Members of funded labs with key roles in the project—such as students, postdocs, and staff—will also participate in scientific meetings, hackathons, and other activities, and relevant members of patient organizations will also be included in such events. The Rare As One team will also expand access to some of its relevant training and support program offerings to both the researchers and organizations that are listed as co-PIs on this grant, and will develop targeted trainings to support this specific collaborative opportunity.
- CZI’s mission is at the interface of technology and science. Working in collaboration with, and guided by, other grantees in the Network and the wider Human Cell Atlas (HCA) community, we aim to develop technology-based tools and approaches to support and accelerate the scope and impact of tissue atlases and the HCA community.
- CZI supports open science values and principles. To accelerate scientific discovery and collaboration, CZI supports a consent, sharing, and publication policy for open and rapid dissemination of research results and a policy for software development that maximizes accessibility, reuse, and shared development.
- CZI believes that the people most affected by problems should be centered in developing solutions to those problems. We work with patient communities to ensure they are heard, and recognize patients and patient communities and organizations as key partners in research.