Fuel for Thought in Neurodevelopmental Disorders

Metabolism is a crucial regulator of brain development, providing the necessary energy for neuronal electrogenesis and overall cerebral functionality. In children, the brain's energy demands are even greater due to significant growth and plasticity, almost 44% of the body's metabolic rate. The metabolic systems responsible for nourishment and energy supply serve as essential fuel for neuronal structures, and abnormalities in their composition can lead to substantial developmental changes.

Despite compelling evidence from decades of research indicating that disrupted energy production—often due to mitochondrial dysfunction or oxidative stress—plays a role in various neurodevelopmental disorders (NDD), there remains a vibrant and complex debate within the scientific community regarding the role of mitochondrial dysfunction in NDDs. Researchers continue to explore whether mitochondrial dysfunction serves as a primary etiological factor driving conditions such as Autism Spectrum Disorder (ASD) and intellectual disability, or whether it arises as a secondary consequence of various underlying stressors, including inflammation, oxidative stress, and non-mitochondrial genetic mutations. This intersection of neurodevelopmental disorders and mitochondrial dysfunction is not just a theoretical concern; it represents a crucial area of ongoing research that seeks to clarify the intricacies of these relationships. The controversies that arise often encompass multiple dimensions, including diagnostic criteria, causative pathways, therapeutic approaches, and the classification of disorders, highlighting the palpable scientific uncertainty and the varying perspectives that clinicians bring to these issues.

This workshop aims to broaden the research focus of NDDs to comprehensively include bio-energetics or brain energy dynamics, particularly emphasizing energy expenditure. By understanding the intricate links between energy metabolism and the onset and progression of NDDs, we can identify treatment development opportunities. This may include novel dietary approaches that optimize substrate availability or metabolic therapies designed to enhance energy production and utilization in the brain. Integrating insights on brain energy dynamics into therapeutic strategies has the potential to improve not just symptom management but also to address core metabolic dysfunctions associated with NDDs, ultimately enhancing developmental outcomes for affected children.

The "Fuel for Thought in NDD" workshop is designed as an international forum where researchers from diverse disciplines can share ideas and collaborate on the essential role of bio-energetics in neurodevelopmental disorders. Aligned with the Lorentz Center's mission, our focus extends beyond what is currently understood, to explore the unknowns in our field and advance clinical and translational research. By fostering an open and interactive atmosphere, we encourage participants to express their questions and curiosity, collectively identifying pathways for future discovery and paving the way for transformative advancements in understanding and treating neurodevelopmental disorders. We strive to translate fragmented insights into a more coherent body of knowledge, ensuring that insights can be deployed more efficiently and in a sustainable way to improve outcomes in neurodevelopmental disorders.

Our primary goals for the week, aimed at creating lasting impact:

Problem definition of bio-energetics after gathering input from participants to initiate and facilitate collaborative research experiments.

Network creation: Based on identifying the expertise of participants and finding common interesting ground, we shape a framework for drafting a comprehensive, overarching review or perspective  paper

Action plan: Obtain insights to develop an innovation framework and research roadmap that can support future grant applications.

Advance practical applications in patient care by enabling more precise treatment stratification based on individual metabolic and genetic profiles.