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Innovative and potential treatments for fungal central nervous system infections
Marta Reguera-Gomez1, Michael R Dores2, Luis R Martinez3
1Department of Oral Biology, College of Dentistry, University of Florida, Gainesville, FL, USA.
Abstract:
Fungal infections of the central nervous system (FI-CNS) are a problematic and important medical challenge considering that those most affected are immunocompromised. Individuals with systemic cryptococcosis (67-84%), candidiasis (3-64%), blastomycosis (40%), coccidioidomycosis (25%), histoplasmosis (5-20%), mucormycosis (12%), and aspergillosis (4-6%) are highly susceptible to develop CNS involvement, which often results in high mortality (15-100%) depending on the mycosis and the affected immunosuppressed population. Current antifungal drugs are limited, prone to resistance, present host toxicity, and show reduced brain penetration, making FI-CNS very difficult to treat. Given these limitations and the rise in FI-CNS, there is a need for innovative strategies for therapeutic development and treatments to manage FI-CNS in at-risk populations. Here, we discuss standards of care, antifungal drug candidates, and novel molecular targets in the blood-brain barrier, which is a protective structure that regulates movement of particles in and out of the brain, to prevent and combat FI-CNS.
Insights
Fungal infections of the central nervous system (FI-CNS) pose a significant threat, especially to immunocompromised individuals. New therapeutic strategies are crucial due to limitations of current antifungal drugs for treating FI-CNS.
Area of Science:
- Medical Mycology
- Neuroscience
- Infectious Diseases
Background:
- Fungal infections of the central nervous system (FI-CNS) disproportionately affect immunocompromised patients.
- Conditions like cryptococcosis, candidiasis, and aspergillosis significantly increase the risk of CNS involvement, leading to high mortality rates.
- Current antifungal treatments are hampered by drug resistance, toxicity, and poor penetration of the blood-brain barrier.
Purpose of the Study:
- To address the challenges in treating fungal infections of the central nervous system (FI-CNS).
- To explore innovative therapeutic development strategies for FI-CNS.
- To identify novel molecular targets for combating FI-CNS in at-risk populations.
Main Methods:
- Review of current standards of care for FI-CNS.
- Analysis of existing and investigational antifungal drug candidates.
- Exploration of novel molecular targets within the blood-brain barrier.
Main Results:
- Current antifungal drugs exhibit limitations including resistance, host toxicity, and inadequate brain penetration.
- High mortality rates associated with FI-CNS underscore the urgent need for improved treatments.
- The blood-brain barrier presents a critical target for enhancing drug delivery and efficacy.
Conclusions:
- Innovative strategies are essential for effective FI-CNS management.
- Targeting the blood-brain barrier offers a promising avenue for novel therapeutic development.
- Addressing the limitations of current antifungals is key to reducing mortality in immunocompromised patients with FI-CNS.
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