NICHD 2025 strategic planning

Dear Colleagues:

NICHD is starting its 2025 Strategic planning.

"NICHD has now released an RFI for public comment on the 2025 Strategic Plan research priorities. We welcome any feedback you have on the priorities noted for the next five years and look forward to reading your responses. You can access the RFI here. The RFI is open for public comment until September 27, 2024.”

NOT-HD-24-028: Request for Information (RFI): NICHD Strategic Plan 2025

grants.nih.gov

Of the five research goals that they list, the top one is:

“Research Goal #1: Understanding the Molecular, Cellular, and Structural Basis of Development

Enhance knowledge of developmental processes and understanding of critical periods in human development, improving understanding of the origins of congenital anomalies, neurodevelopmental disorders, and intellectual and developmental disabilities.

Opportunities: This goal includes a focus on understanding developmental processes by describing the intrinsic events that contribute to early human development. This goal will also focus on exploring how extrinsic factors can influence developmental and physiological processes, particularly in the context of congenital anomalies, neurodevelopmental disorders, and intellectual and developmental disabilities. Additionally, this goal aims to enhance collaborative developmental biology research by investing in improved infrastructure—along with novel tools and technologies—to analyze and validate data derived from model systems research, biophysics, biomechanics, optogenetics, and other emerging scientific areas. This research area will also support the use of genomics, proteomics, and metabolomics to profile gene and protein expression and regulation at the single-cell level and characterize regulatory networks across tissues and time during development.”

We note that the other four goals seem less related to birth defects and embryonic development.  Given our collective interest in embryonic development and its impact on human health, it is imperative that we all respond to the RFI and highlight the importance of focusing resources on this #1 research goal.

To that end, please respond to the RFI to help amplify the voices from our community.

Responses should be submitted via email to NICHDStrategicPlan@nih.gov, no later than Friday, September 27, 2024. Please indicate RFI Response in the subject line of the email. 

In order to make it as easy as possible to send this email, we offer the following template. Please consider modifying and sending to NICHD.  Also please feel free to forward to other interested folks, research, and clinical communities.

Mustafa Khokha, Yale University
Rolf Stottmann, Nationwide Children’s
Irene Zohn, Children’s National

Dear NICHD Strategic Planning Group:

I write to emphasize the critical importance of Research Goal #1. Congenital anomalies are the #1 cause of infant mortality, mortality of children under five, and hospitalizations of children and therefore should be a primary importance for NICHD. In fact, I am delighted that NICHD has listed Understanding the basis of development as the #1 goal and hope that resources would be primarily dedicated towards addressing this major health problem.

I wholeheartedly agree that a strong emphasis in the next strategic plan should be to support Research Goal #1 as listed in the current RFI. In fact, the development biology research community and physicians caring for children with congenital anomalies is drafting a white paper to summarize the state of research on congenital anomalies. Our community identifies a number of key priorities and opportunities in this area of research. For me a critical issue is the following:

---INSERT priority from the list below: this is the list of 6 major points identified by the congenital anomaly community and serves as a high-level summary of the white paper.---

My view is that advancing our understanding of embryonic development is essential to attack the scourge of congenital anomalies that afflicts young children in the US more than any other disease. I strongly recommend that the NICHD allocate resources to address this problem as well as work with other Institutes in collaboration to support work on other organ specific congenital anomalies. Addressing the gaps in knowledge in the causes, treatment and prevention of congenital anomalies will require cross disciplinary collaborations. Child health starts with development of healthy newborns as congenital anomalies are the most common cause of infant death in the US. This should be the primary health issue of NICHD, which will make a tremendous impact on the health of our children worldwide.

Sincerely

XXX
 

1.   Congenital Anomalies are prevalent and are the #1 cause of infant mortality.

Congenital anomalies are structural or functional abnormalities that originate before birth.  Congenital anomalies are the leading cause of infant mortality and hospitalizations of children in the United States and Europe. Children with congenital anomalies require expensive and ongoing medical care to treat chronic illness and disability. Despite being a major societal issue, the public is generally unaware of the impact, so the resources allocated to investigating the causes of congenital anomalies are disproportionately low. To change this, educating the public about the impact of congenital anomalies on patients, families, caregivers, and society will be crucial. Finding the causes of congenital anomalies will be transformative for patients by allowing them to access targeted medical interventions, education, genetic counseling, and research studies of long-term outcomes of the specific disorder. Additionally, specific molecular diagnoses enable community building of similarly affected patients for social support, primarily via social media. Thus, public support of increased funding to identify the causes of congenital anomalies will significantly improve the lives of affected children.

2.   Scientists are making progress in identifying the causes of congenital anomalies, but more work remains.

Although scientists have made significant strides in identifying the causes of many congenital anomalies, countless patients and families still do not know the molecular basis of their disease and are seeking answers. Known causes of congenital anomalies include chromosomal disorders, single-gene defects, multifactorial inheritance, and environmental factors such as micronutrient malnutrition and maternal illness. Because of recent technological advances, the discovery of the genetic basis of congenital malformations has never been more tractable. However, genotype-phenotype correlations can be variable; in some cases, variants in a gene can lead to predictable phenotypes, while in other cases, vastly different anomalies. Despite these complexities, gene discovery in congenital anomalies is challenging but achievable. Importantly, identifying the genetic basis of congenital anomalies enables the generation of experimental models that can be used to study the underlying developmental mechanisms of the disorder and develop treatments. The genetic basis of congenital anomalies is diverse, and understanding the molecular mechanisms can have broad implications and can be leveraged across many diseases.

3. Genome Sequencing is cost-effective but underutilized.

The genetic causes of many congenital anomalies are still unknown, but advances in DNA and RNA sequencing technologies continue to improve our understanding. The clinical investigation into the cause of a congenital anomaly can involve a complex “diagnostic odyssey,” subjecting fragile children to months or years of tests and referrals that may still fail to make a diagnosis. Genome sequencing can mitigate this diagnostic odyssey, and children with congenital anomalies should have early access to genetic testing. In addition, the cost of a one-time genome sequence test in young children can be reused in multiple future medical encounters. This facilitates the application of precision medicine approaches to improve their care and enrollment in clinical trials. Evidence-based research into how best to implement and integrate genomic screening into clinical practice and research is needed. Importantly, genomic sequencing results must be incorporated into the medical record and fully exploited to improve care. Broad-based genomic sequencing can systemically reduce racial disparities in healthcare access. Using sequencing in this way will improve patient care for everyone.

4. Identification of sequence variants is not enough; functional testing of suspected variants and elucidation of the molecular mechanisms of disease pathogenesis will improve diagnosis and treatment.

Our capacity to identify genetic variants is outpacing our ability to interpret them. To complement the diagnostic advantage of genome sequencing, functional studies of identified genetic variants, especially the genes and variants of unknown significance (VUS), and their association with disease pathogenesis are essential. Understanding the functional significance of genetic variation increases diagnostic precision, uncovers disease pathogenesis to identify new therapeutic options, and, more generally, increases fundamental knowledge of human biology. Multiple complementary biological model systems are essential for efficient functional testing of suspected variants. Flexible funding mechanisms to encourage experimental modeling of candidate genes/variants will be crucial to achieving this goal. Resources are required to analyze, curate, integrate, and disseminate data generated from functional studies. This will be key to understanding the complex and interconnected relationships among the genes, variants, and environmental factors underlying congenital anomalies.

5. Congenital Anomaly research requires a collaborative understanding of patient phenotype, genetic variation, and biological mechanisms.

Congenital anomalies research requires input from disparate fields of biology and the clinic. We must improve communication between clinicians and bench scientists to advance the field. Moreover, incentives are needed to facilitate the participation of clinical providers and their patients in research studies. Focused grant funding with special study sections to encourage preliminary scientific investigations and interdisciplinary translational research on congenital anomalies will be essential to accelerate discoveries and improve the lives of patients/families.

6. Return of results to patients/families and potential for treatments can have an extraordinary impact.

Etiologies of congenital anomalies can be ultra-rare and lead to feelings of isolation and desperation to get answers. As recently recommended by the National Academies (2018), it is therefore imperative that patients and families be treated as participants in research, meaning individual research results should be returned to patients, families, and clinicians while fostering an understanding of implications and limitations. The return of research results creates transparency in the research endeavor and offers multiple benefits for patients/families. These include 1) an appreciation of the scientific efforts to understand the cause and pathogenesis of the disorder, which affects a family’s well-being, 2) a needed sense of support from the researchers, 3) an opportunity to connect with other families with shared experience often through social media and 4) hope for potential treatments if not for themselves than for future patients. Patients with congenital anomalies have few therapeutic options beyond surgery; improving this is a critical need for the future of precision medicine.