About this Research Topic

Background

Diseases of the CNS exact an enormous toll on global health and novel therapies are desperately needed to relieve the burdens of patients and their caregivers.
Mitochondria are critical for cellular metabolism and also play key roles in intracellular signaling and response to cellular stress. The CNS has extremely high metabolic demand and is critically dependent on functional mitochondria. In fact, dysregulated mitochondrial function is implicated in a wide range of CNS pathologies, including neurodegenerative, neurodevelopmental, and psychiatric diseases. Numerous groups within academia and industry have recognized the key impact of mitochondrial dysfunction in CNS diseases, driving forward our understanding of mitochondrial biology in the CNS, and resulting in novel targets and approaches for drug discovery and development.

This Research Topic will provide a forum to highlight these important advances and provide insights into active drug discovery and development pipelines.

The critical role of dysregulated mitochondrial function and signaling in CNS diseases has long been recognized. Among the rare mitochondrial diseases such as MELAS, LHON and Leigh Syndrome many patients suffer from devastating CNS symptoms, including seizures, fatigue, motor impairment, cognitive decline, visual sequelae, and psychiatric manifestations. More broadly, many neurodegenerative, neurodevelopmental, and psychiatric diseases have mitochondrial dysfunction at the core of their pathology, potentially as one of the earliest manifestations of disease.
Unfortunately, the development of therapies targeting mitochondrial dysfunction has lagged behind our recognition of the impact mitochondria have on disease., Previous therapies have broadly targeted the output of dysregulated mitochondria in the forms of nutritional supplements, antioxidants and nutraceuticals yielding modest if any effects on disease. More recently, high-profile academic and seasoned drug discovery teams have turned their attention to bringing forward the next generation of therapies specifically targeting the core aspects of mitochondrial dysfunction and advancing these approaches to address a range of rare and complex CNS diseases.

This Research Topic will highlight many of these incredible advances and provide a venue to discuss critical learnings from the field to advance the next generation of CNS therapies specifically targeting mitochondrial dysfunction.

The scope will cover pharmacology studies describing mechanistic connections between mitochondrial dysfunction and CNS diseases, novel targets for pharmacological intervention, characterization of pharmacological and translational biomarkers or biomarker strategies, as well as clinical pharmacology studies and clinical evaluations of novel therapies. The specific themes addressed in this Research Topic include:

• Identification and validation of novel targets correcting mitochondrial dysfunction for CNS diseases
• Pharmacological approaches to evaluate new mechanisms of action
• Diverse modalities for therapeutic intervention
• Examples of translational pharmacology approaches
• Alignment of nonclinical and clinical biomarkers to demonstrate target engagement, improvement of mitochondrial function and impact on disease progression, to facilitate development of new therapies
• Clinical pharmacology study results and early evaluations in patients.

Contributions that will be considered for publication in this Research Topic include primary research papers, clinical reports, or comprehensive reviews of current approaches for the discovery and development of therapies targeting mitochondrial dysfunction in CNS diseases.


Christopher J. Winrow is a full-time employee of Lucy Therapeutics, and holds equity (shares, stock, stock options, and/or restricted stock units) in Lucy Therapeutics, and from previous employers Cyclerion Therapeutics and Ironwood Pharmaceuticals.

Dr. Manfredi serves on the scientific advisory board of Larimar Therapeutics and Lucy Therapeutics and as a consultant for Relmada Therapeutics, Neurogene Therapeutics, and Stealth Therapeutics

Peter Lansbury has consulting agreements (equity holding indicated by (*)) with: Aliada Therapeutics (*), Bial Pharma, Congruence Therapeutics, Gain Therapeutics, Immvention, Jaya Therapeutics (*), Kynexis Therapeutics, Lucy Therapeutics (*), Minerva Biosciences (*), Vincere Therapeutics (*).

Dr. Andreazza is the Founder and Scientific Director of the Mitochondrial Innovation Initiative (MITO2i) which is an Institutional Strategic Initiative (ISI) at the University of Toronto since March 2020. MITO2i delivers a collaborative hub that engages all stakeholders in advancing science in the field of mitochondrial medicine & research. Dr. Andreazza is funded by CCRM which supports the commercialization of regenerative medicine-based technologies, and cell and gene therapies. Both do not offer COI for this project.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Clinical Trial
• Community Case Study
• Data Report
• Editorial
• General Commentary
• Hypothesis and Theory
• Methods
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Clinical Trial
• Community Case Study
• Data Report
• Editorial
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Study Protocol
• Systematic Review
• Technology and Code

Keywords: mitochondrial dysfunction, CNS therapies, rare diseases, neurodegenerative diseases

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