Mitochondrion-targeted RNA therapies as a potential treatment strategy for mitochondrial diseases

Molecular Therapy — Nucleic Acids, Journal Year: 2022, Volume and Issue: 30, P. 359 - 377

Published: Oct. 27, 2022

Mitochondrial diseases are one of the largest groups neurological genetic disorders. Despite continuous efforts scientific community, no cure has been developed, and most treatment strategies rely on managing symptoms. After success coronavirus disease 2019 (COVID-19) mRNA vaccines accelerated US Food Drug Administration (FDA) approval four new RNAi drugs, we sought to investigate potential mitochondrion-targeting RNA-based therapeutic agents for mitochondrial diseases. Here describe causes existing therapies We then detail diseases, including use antisense oligonucleotides (ASOs) allotopic therapies, antigenomic that aim decrease level deleterious heteroplasmy in affected tissues. Finally, review different mechanisms by which can be delivered matrix, mitochondrion-targeted nanocarriers endogenous RNA import pathways.

Language: Английский

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Advancements in ultrasound-mediated drug delivery for central nervous system disorders

Expert Opinion on Drug Delivery, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 16

Published: Dec. 3, 2024

Central nervous system (CNS) disorders present major therapeutic challenges due to the presence of blood - brain barrier (BBB) and disease heterogeneity. The BBB impedes most agents, which restricts conventional treatments. Focused ultrasound (FUS) -assisted delivery offers a novel solution by temporarily disrupting thereby enhancing drug CNS.

Language: Английский

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Noncoding RNA therapeutics for substance use disorder

Advances in Drug and Alcohol Research, Journal Year: 2022, Volume and Issue: 2

Published: Dec. 20, 2022

Although noncoding RNAs (ncRNAs) have been shown to regulate maladaptive neuroadaptations that drive compulsive drug use, ncRNA-targeting therapeutics for substance use disorder (SUD) yet be clinically tested. Recent advances in RNA-based drugs improved many therapeutic issues related immune response, specificity, and delivery, leading multiple successful clinical trials other diseases. As the need safe effective treatments SUD continues grow, novel nucleic acid-based represent an appealing approach target ncRNA mechanisms SUD. Here, we review processes implicated SUD, discuss recent approaches targeting ncRNAs, highlight potential opportunities challenges of

Language: Английский

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Biodistribution of Radioactively Labeled Splice Modulating Antisense Oligonucleotides After Intracerebroventricular and Intrathecal Injection in Mice

Nucleic Acid Therapeutics, Journal Year: 2024, Volume and Issue: 34(1), P. 26 - 34

Published: Feb. 1, 2024

Antisense oligonucleotides (AONs) are promising therapeutic candidates, especially for neurological diseases. Intracerebroventricular (ICV) injection is the predominant route of administration in mouse studies, while clinical trials, intrathecal (IT) mostly used. There little knowledge on differences distribution these methods within same species over time. In this study, we compared splice-switching AONs targeting exon 15 amyloid precursor protein pre-mRNA injected via ICV and IT mice. The AON was labeled with radioactive indium-111 mice were imaged using single-photon emission computed tomography (SPECT) 0, 4, 24, 48, 72, 96 h after injection. vivo SPECT imaging showed 111In-AON activity diffused throughout central nervous system (CNS) first hours CNS persisted course 4 days, signal kidneys rapidly decreased. Postmortem counting different organs tissues very similar body, brain regions higher Overall, have patterns mouse, but much more effective reaching brain.

Language: Английский

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Insights of nose to brain delivery in treating Parkinson’s disease: A systematic review

Journal of Applied Pharmaceutical Research, Journal Year: 2024, Volume and Issue: 12(6), P. 57 - 72

Published: Dec. 31, 2024

Background: In Parkinson's disease (PD), a complicated neurodegenerative ailment, neurons in the substantia nigra that produce dopamine are lost, resulting an insufficiency of neurotransmitter is essential for regulation voluntary and smooth muscular movements. This review focuses on obstacle triggering effectiveness traditional PD treatments, which blood-brain barrier (BBB), prevents some therapeutic medicines from reaching brain. It encompasses potential strategy nose-to-brain administration by innovative approaches, including nanoparticles, liposomes, dendrimers, cell-based carriers, directly delivering drugs nose to Methods: The methodology involved examining characteristics, advantages, applications, challenges various nanoparticles like SLNs, Nanoliposomes, Quantum dots, etc., through meticulous analysis articles PubMed (5), ScienceDirect Bentham Science (4) Scopus databases (5). Conclusion: concludes emphasizing applications circumventing problems encountered with methods drug treating PD. detailed study brings light need be faced utilizing delivery. Attention directed towards enlightenment advanced carriers target specific brain regions via olfactory trigeminal routes. reaches brain, bypassing BBB.

Language: Английский

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