Strategic Drug Development for Rare and Underexplored Diseases

While significant progress has been made in developing treatments for rare diseases—highlighted by the approval of over 800 drugs for orphan diseases since the Orphan Drug Act was enacted in the US in 1983, and further supported by similar regulatory incentives such as the European Medicines Agency’s (EMA) Orphan Medicinal Product Regulation introduced in 2000—many conditions, particularly those affecting smaller or underserved populations, continue to present substantial unmet medical needs. Despite growing regulatory and commercial efforts on both sides of the Atlantic, these underexplored diseases often still face hurdles such as limited commercial incentives, complex pathophysiologies, and challenges in conducting large-scale clinical trials. This complexity underscores the need for ongoing innovation and strategic approaches within drug development, especially as new orphan drugs move beyond clinical trial settings and into wider real-world use.

This Research Topic aims to explore new strategies for drug development targeting underexplored diseases. We will delve into various innovative approaches that can overcome traditional barriers in drug discovery, exemplifying how collaborative efforts, advanced technologies, and strategic planning can accelerate the development of therapeutics for these neglected conditions. Contributors are encouraged to address topics such as:

1. Target Identification and Validation:

o Utilizing high-throughput screening technologies and bioinformatics to identify novel drug targets in underexplored diseases.

o Exploring the role of genomics, proteomics, and metabolomics in understanding disease mechanisms and identifying potential therapeutic targets.

o Developing cellular models (iPSCs, 3D organoids, etc.) and mouse models to mimic rare diseases and provide key information on mechanisms and therapeutic strategies.

o Advancing genomics to identify causal variants and facilitate rare disease diagnosis.

2. Innovative Drug Discovery and Development Techniques:

o Implementing novel virtual screening methods and algorithms based on machine learning and artificial intelligence (AI) to expedite the identification of promising hit compounds.

o Creating and screening chemical libraries (small molecules) with biological relevance and structural diversity to accelerate drug discovery and development.

o Exploring natural products and traditional medicine as sources of new therapeutic agents.

o Encouraging drug repositioning of approved and existing drugs for new indications to accelerate the treatment development process for rare diseases.

o Applying Model-informed Drug Discovery and Development (MID3) strategies for rare and underexplored diseases

3. Collective Strategies and Partnerships:

o Analyzing successful case studies of public-private partnerships and multi-stakeholder collaborations that have led to the development of drugs for underexplored diseases.

o Discussing frameworks that encourage sharing data and resources, such as open-access platforms and consortia.

4. Case Studies and Clinical Trials:

o Presenting novel case studies that highlight successes and failures in drug development for neglected diseases.

o Discussing challenges and strategies in designing and conducting clinical trials for small patient populations.

5. Real-World Evidence and Monitoring of Orphan Drug Outcomes:

o Collecting and analyzing real-world evidence to assess the effectiveness and safety of orphan drugs in broader patient populations.

o Developing methodologies for ongoing monitoring of orphan drug outcomes to ensure long-term safety and efficacy.

o Exploring strategies for post-market surveillance and data collection to understand the impact of orphan drugs beyond clinical trial settings.

o Evaluating tools and technologies for real-time data capture and analysis for better monitoring orphan drug benefits and risks.

The goal of this Research Topic is to bring together diverse perspectives and expertise, fostering a comprehensive discussion on enhancing the drug development pipeline for underexplored diseases. Insights from these contributions can pave the way for more equitable healthcare solutions and inspire further research in the field.

Considerations for Authors:

We welcome original research articles, reviews, and case studies that offer rigorous and innovative perspectives on the strategic drug development for underexplored diseases. Submissions should provide well-supported analysis and propose actionable strategies that can be applied to current pharmaceutical challenges.

For manuscripts that focus on natural compounds, please utilize the ConPhyMP tool and ensure compliance with the standards outlined in the ConPhyMP statement (Front. Pharmacol. 13:953205). Additionally, compliance with the Four Pillars of Best Practice in Ethnopharmacology is mandatory. You can freely download the full version here. A comprehensive description of the studied material, including its identified source, extraction and processing methods, and clear composition, is essential.

Please note that submissions lacking experimental validation of in silico findings will not be considered.

Article types and fees

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

• Brief Research Report
• Data Report
• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• ... 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
• Data Report
• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Systematic Review
• Technology and Code

Keywords: Underexplored Diseases, Drug Development, Target Identification, High-Throughput Screening, Bioinformatics, Genomics, Proteomics, Metabolomics, Cellular Models, Ipscs, 3D Organoids, Mouse Models, Rare Diseases, Drug Discovery, Orphan Drugs

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.