mRNA Abundance of Neurogenic Factors Correlates with Hearing Capacity in Auditory Brainstem Nuclei of the Rat DOI Creative Commons
Jonas Engert, Julia Doll, Barbara Vona

et al.

Life, Journal Year: 2023, Volume and Issue: 13(9), P. 1858 - 1858

Published: Sept. 2, 2023

Neural stem cells (NSCs) have previously been described up to the adult stage in rat cochlear nucleus (CN). A decreasing neurogenic potential was observed with critical changes around hearing onset. better understanding of molecular factors affecting NSCs and neurogenesis is interest as they represent targets treat cause neurologically based disorders. The role genes NSC development CN over time on capacity has remained unclear. This study investigated mRNA abundance influencing rats' time. rats postnatal days 6, 12, 24 were examined. Real-time quantitative polymerase chain reaction arrays used compare levels 84 relevant neurogenesis. Age- hearing-specific patterns neurogenically detected CN. Additionally, crucial significant influence identified. results this work should contribute a mechanisms underlying auditory pathway.

Language: Английский

Autosomal Dominant Non-Syndromic Hearing Loss (DFNA): A Comprehensive Narrative Review DOI Creative Commons
Mirko Aldè, Giovanna Cantarella, Diego Zanetti

et al.

Biomedicines, Journal Year: 2023, Volume and Issue: 11(6), P. 1616 - 1616

Published: June 1, 2023

Autosomal dominant non-syndromic hearing loss (HL) typically occurs when only one allele within the disease gene is sufficient to express phenotype. Therefore, most patients diagnosed with autosomal HL have a hearing-impaired parent, although de novo mutations should be considered in all cases of negative family history. To date, more than 50 genes and 80 loci been identified for HL. DFNA22 (MYO6 gene), DFNA8/12 (TECTA DFNA20/26 (ACTG1 DFNA6/14/38 (WFS1 DFNA15 (POU4F3 DFNA2A (KCNQ4 DFNA10 (EYA4 gene) are some common forms The characteristics heterogenous. However, cases, tends bilateral, post-lingual onset (childhood early adulthood), high-frequency (sloping audiometric configuration), progressive, variable severity (mild profound degree). DFNA1 (DIAPH1 affecting low frequencies, while DFNA16 (unknown characterized by fluctuating A long audiological follow-up paramount importance identify threshold deteriorations ensure prompt treatment aids or cochlear implants.

Language: Английский

Citations

43
PCDH15 Dual-AAV Gene Therapy for Deafness and Blindness in Usher Syndrome Type 1F Models DOI Creative Commons
Maryna V. Ivanchenko, Daniel M. Hathaway, Eric M. Mulhall

et al.

Journal of Clinical Investigation, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 15, 2024

Usher syndrome type 1F (USH1F), resulting from mutations in the protocadherin-15 (PCDH15) gene, is characterized by congenital lack of hearing and balance, progressive blindness form retinitis pigmentosa. In this study, we explore an approach for USH1F gene therapy, exceeding single AAV packaging limit employing a dual adeno-associated virus (AAV) strategy to deliver full-length PCDH15 coding sequence. We demonstrate efficacy mouse models, effectively restoring balance these mice. Importantly, our also proves successful expressing protein clinically relevant retinal including human organoids non-human primate retina, showing efficient targeting photoreceptors proper expression calyceal processes. This research represents major step toward advancing therapy multiple challenges hearing, vision impairment.

Language: Английский

Citations

8
Gene Therapy for Inherited Hearing Loss: Updates and Remaining Challenges DOI Creative Commons

Roni Hahn,

Karen B. Avraham

Audiology Research, Journal Year: 2023, Volume and Issue: 13(6), P. 952 - 966

Published: Dec. 4, 2023

Hearing loss stands as the most prevalent sensory deficit among humans, posing a significant global health challenge. Projections indicate that by 2050, approximately 10% of world’s population will grapple with disabling hearing impairment. While half congenital cases have genetic etiology, traditional interventions such aids and cochlear implants do not completely restore normal hearing. The absence biological treatment has prompted efforts in recent years, strong focus on gene therapy to address hereditary loss. Although several studies exhibited promising recovery from common forms deafness mouse models, existing challenges must be overcome make applicable near future. Herein, we summarize primary strategies employed over past provide an overview achievements preclinical for loss, outline current key obstacles therapy.

Language: Английский

Citations

12
The Opportunities and Challenges of Gene Therapy for Treatment of Inherited Forms of Vision and Hearing Loss DOI

Emmanuel J. Simons,

Ivana Trapani

Human Gene Therapy, Journal Year: 2023, Volume and Issue: 34(17-18), P. 808 - 820

Published: Aug. 29, 2023

Inherited forms of blindness and deafness are highly prevalent severe conditions that significantly impact the lives millions people worldwide. The lack therapeutic options for these poses a major socioeconomic burden. Over last decades, gene therapy has proven to be life changing treatment hereditary acquired diseases, extensive preclinical investigation in animal models both retinal inner ear disorders highlighted promising translational opportunities too. This led dozens clinical trials investigating efficiency therapy-based approaches, with some products successfully reaching phase III development or even market authorization. However, challenges remain use therapy, which related features delivery vehicles currently available characteristics targeted. Therefore, further developments platforms' design, including exploitation novel technologies such as genome editing, RNA-targeted therapies, optogenetics, actively ongoing, driving field forward. In this study, we review ongoing applications achievements inherited well being pursued overcome current limitations.

Language: Английский

Citations

10
Cell tropism of adeno-associated viruses within the mouse inner ear in vivo: from embryonic to adult stages DOI Creative Commons

Sepideh Iranfar,

Maxence Cornille,

M Roldán

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 18, 2025

Language: Английский

Citations

0
Recent advances and future challenges in gene therapy for hearing loss DOI Creative Commons
Ana E. Amariutei, Jing‐Yi Jeng, Saaïd Safieddine

et al.

Royal Society Open Science, Journal Year: 2023, Volume and Issue: 10(6)

Published: June 1, 2023

Hearing loss is the most common sensory deficit experienced by humans and represents one of largest chronic health conditions worldwide. It expected that around 10% world's population will be affected disabling hearing impairment 2050. Hereditary accounts for known forms congenital deafness, over 25% adult-onset or progressive loss. Despite identification well 130 genes associated with there currently no curative treatment inherited deafness. Recently, several pre-clinical studies in mice exhibit key features human deafness have shown promising recovery through gene therapy involving replacement defective a functional one. Although potential application this therapeutic approach to closer than ever, substantial further challenges need overcome, including testing safety longevity treatment, identifying critical time windows improving efficiency treatment. Herein, we provide an overview recent advances highlight current hurdles scientific community overcome ensure safe secure implementation clinical trials.

Language: Английский

Citations

9
In utero adeno-associated virus (AAV)-mediated gene delivery targeting sensory and supporting cells in the embryonic mouse inner ear DOI Creative Commons
Carla Maria Barbosa Spinola, Jacques Boutet de Monvel,

Saaid Safieddine

et al.

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(7), P. e0305742 - e0305742

Published: July 19, 2024

In vivo gene delivery to tissues using adeno-associated vector (AAVs) has revolutionized the field of therapy. Yet, while sensorineural hearing loss is one most common sensory disorders worldwide, therapy applied human inner ear still in its infancy. Recent advances development recombinant AAVs have significantly improved their cell tropism and transduction efficiency across diverse types a level that renders this tool valuable for conditionally manipulating expression context developmental biology studies mouse ear. Here, we describe protocol utero micro-injection into embryonic ear, AAV-PHP.eB AAV-DJ serotypes respectively target hair cells supporting auditory epithelium. We also aimed standardize procedures imaging acquisition image analysis foster research reproducibility allow accurate comparisons between studies. find provide efficient reliable tools conditional targeting cochlear from late stages on.

Language: Английский

Citations

3
Gene editing in common cardiovascular diseases DOI Creative Commons
Anna-Maria Lauerer, Xurde M. Caravia, Lars S. Maier

et al.

Pharmacology & Therapeutics, Journal Year: 2024, Volume and Issue: unknown, P. 108720 - 108720

Published: Sept. 1, 2024

Language: Английский

Citations

3
Update on Gene Therapy in the Treatment of Hereditary Hearing Loss DOI Creative Commons
Weiwei He, Shanying Han,

Xinghong Liu

et al.

Published: May 7, 2025

ABSTRACT Gene therapy is a promising therapeutic approach for genetic disorders, involving modification to repair or reconstruct faulty material. It particularly relevant hereditary hearing loss (HHL), common monogenic condition that can lead congenital deafness. The recent approval of clinical trial results using gene HHL underscores the growing interest in this field. To further advance inner ear and its application diseases, it crucial review progress HHL. This focuses on three major strategies—gene replacement, suppression, editing—highlighting their across different disorders successful preclinical trials We summarize primary strategies used years, discuss achievements studies, explore potential advancements

Language: Английский

Citations

0
The Role of Pericytes in Inner Ear Disorders: A Comprehensive Review DOI Creative Commons
Antonino Maniaci, Marilena Briglia,

Fabio Allia

et al.

Biology, Journal Year: 2024, Volume and Issue: 13(10), P. 802 - 802

Published: Oct. 8, 2024

Inner ear disorders, including sensorineural hearing loss, Meniere’s disease, and vestibular neuritis, are prevalent conditions that significantly impact the quality of life. Despite their high incidence, underlying pathophysiology these disorders remains elusive, current treatment options often inadequate. Emerging evidence suggests pericytes, a type vascular mural cell specialized to maintain integrity function microvasculature, may play crucial role in development progression inner disorders. The pericytes present microvasculature both cochlea system, where they regulate blood flow, blood–labyrinth barrier, facilitate angiogenesis, provide trophic support neurons. Understanding valuable insights into lead novel diagnostic therapeutic strategies, improving standard living. This comprehensive review aims detailed overview highlighting anatomy physiology analyzing mechanisms contribute Furthermore, we explore potential pericyte-targeted therapies, antioxidant, anti-inflammatory, angiogenic approaches, as well gene therapy strategies.

Language: Английский

Citations

2