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Last update 08 May 2025

Kv7.4

Last update 08 May 2025

Basic Info

Synonyms

DFNA2, KCNQ4, KQT-like 4

+ [7]

Introduction

Pore-forming subunit of the voltage-gated potassium (Kv) channel involved in the regulation of sensory cells excitability in the cochlea (PubMed:10025409, PubMed:34767770). KCNQ4/Kv7.4 channel is composed of 4 pore-forming subunits assembled as tetramers (PubMed:34767770). Promotes the outflow of potassium ions in the repolarization phase of action potential which plays a role in regulating membrane potential of excitable cells (PubMed:10025409, PubMed:11245603, PubMed:34767770). The channel conducts a slowly activating and deactivating current (PubMed:10025409, PubMed:11245603). Current often shows some inward rectification at positive potentials (PubMed:10025409). Channel may be selectively permeable in vitro to other cations besides potassium, in decreasing order of affinity K(+) = Rb(+) > Cs(+) > Na(+) (PubMed:10025409). Important for normal physiological function of inner ear such as sensory perception of sound (PubMed:10025409, PubMed:10369879).

Drugs associated with Kv7.4

Bimokalner

Target

Kv7.4

Mechanism

Kv7.4 stimulators

Active Org.

Acousia Therapeutics GmbH

Originator Org.

Acousia Therapeutics GmbH

Active Indication

Hearing Loss [+1]

Inactive Indication-

Drug Highest PhasePhase 2

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

ML213

Target

Kv7.2 x Kv7.4

Mechanism

Kv7.2 agonists [+1]

Active Org.

The Johns Hopkins University

Originator Org.

The Johns Hopkins University

Active Indication

Nervous System Diseases

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

ACOU082

Target

Kv7.4

Mechanism

Kv7.4 stimulators

Active Org.

Acousia Therapeutics GmbH

Originator Org.

Acousia Therapeutics GmbH

Active Indication

Presbycusis

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with Kv7.4

NCT06521190

/ RecruitingPhase 2

Phase IIa Randomized, Double-blind, and Placebo-controlled Multicenter Split Body Trial of Repeated Doses of ACOU085 for the Prevention of Hearing Loss in Testicular Cancer Patients Receiving Cisplatin

Randomized, double-blind, placebo-controlled, multicenter phase IIa clinical trial in adult male TCa patients with the risk to suffer from sensorineural hearing loss (SNHL) due to cisplatin therapy within a chemotherapeutic regimen of testicular cancer. Patients will have an indication for a cisplatin-containing chemotherapy according to current guidelines and trial site tumor board recommendations. The trial is designed to show efficacy, safety, and tolerability of ACOU085 administered into the middle ear using 3 transtympanic injections per ear prior to 3 planned and corresponding 3-week chemotherapeutic cycles. The intra-individual control will be done by placebo injection into the respective contralateral middle ear.

Start Date15 Dec 2023

Sponsor / Collaborator

Acousia Therapeutics GmbH

100 Clinical Results associated with Kv7.4

100 Translational Medicine associated with Kv7.4

0 Patents (Medical) associated with Kv7.4

359

Literatures (Medical) associated with Kv7.4

01 Mar 2025·Molecular Genetics & Genomic Medicine

A KCNQ4 Gene Variant (c.701A > G; p.His234Arg) in a Chinese Family With Nonsyndromic Deafness 2A

Article

Author: Huang, Cheng‐Cheng ; Cao, Jing‐Yuan ; Zhang, Zhao ; Gong, Guo‐Qing ; Sun, Yi ; Lu, Yu ; Yang, Yue‐Bin ; Li‐Wang ; Yang, Guang ; Chen, Rui‐Yao ; Lu, Hui‐Fang ; Ji, Yi‐Ming ; Jin, Hui‐Yu ; Yang, Chang‐Liang

ABSTRACTBackgroundKCNQ4 is a common genetic cause of nonsyndromic autosomal dominant hearing loss. We have identified the family in China with a KCNQ4 (c.701A>G; p.His234Arg) missense variation. In this study, a survey and analysis were performed to investigate the audiological and genetic characteristics of the Chinese family.MethodsThe medical history of family members was collected, and the family members underwent pure tone audiometry, acoustic immittance, and physical examination. The proband was additionally examined by ABR (auditory brainstem response) and DPOAE (distortion product otoacoustic emission). DNA samples from family members were collected, and the possible causative gene of the proband was detected by whole‐exome sequencing (WES), which was verified by Sanger sequencing in family members.ResultsThe inheritance pattern of the family was an autosomal dominant nonsyndromic type. The hearing loss was characterized by postlingual deafness, high‐frequency hearing loss in the early stage, gradually involving the full frequency. About 32–40 years of age, the hearing gradually became stable, the decline rate slowed down, and the final degree of hearing loss was severe. WES results showed that the KCNQ4 gene had a missense variation (c.701A>G; p.His234Arg).ConclusionThis family has autosomal dominant nonsyndromic hereditary hearing loss caused by a variation in the KCNQ4 gene, characterized by high‐frequency hearing loss.

01 Jan 2025·Human Genetics

Genetic landscape in undiagnosed patients with syndromic hearing loss revealed by whole exome sequencing and phenotype similarity search

Article

Author: Mutai, Hideki ; Nakano, Atsuko ; Kikkawa, Yoshiaki ; Arimoto, Yukiko ; Minami, Shujiro ; Fujioka, Masato ; Kawasaki, Taiji ; Tsunoda, Tatsuhiko ; Morimoto, Noriko ; Inoue, Satomi ; Matsunaga, Tatsuo ; Shitara, Hiroshi ; Miya, Fuyuki ; Yamamoto, Nobuko ; Uchida, Yasue ; Namba, Kazunori ; Kosaki, Kenjiro ; Yamazawa, Kazuki ; Kaga, Kimitaka ; Murakami, Haruka ; Nara, Kiyomitsu ; Wasano, Koichiro

There are hundreds of rare syndromic diseases involving hearing loss, many of which are not targeted for clinical genetic testing. We systematically explored the genetic causes of undiagnosed syndromic hearing loss using a combination of whole exome sequencing (WES) and a phenotype similarity search system called PubCaseFinder. Fifty-five families with syndromic hearing loss of unknown cause were analyzed using WES after prescreening of several deafness genes depending on patient clinical features. Causative genes were identified in 22 families, including both established genes associated with syndromic hearing loss (PTPN11, CHD7, KARS1, OPA1, DLX5, MITF, SOX10, MYO7A, and USH2A) and those associated with nonsyndromic hearing loss (STRC, EYA4, and KCNQ4). Association of a DLX5 variant with incomplete partition type I (IP-I) anomaly of the inner ear was identified in a patient with cleft lip and palate and acetabular dysplasia. The study identified COL1A1, CFAP52, and NSD1 as causative genes through phenotype similarity search or by analogy. ZBTB10 was proposed as a novel candidate gene for syndromic hearing loss with IP-I. A mouse model with homozygous Zbtb10 frameshift variant resulted in embryonic lethality, suggesting the importance of this gene for early embryonic development. Our data highlight a wide spectrum of rare causative genes in patients with syndromic hearing loss, and demonstrate that WES analysis combined with phenotype similarity search is a valuable approach for clinical genetic testing of undiagnosed disease.

01 Jan 2025·BIO-PROTOCOL

Proximity Labelling to Quantify Kv7.4 and Dynein Protein Interaction in Freshly Isolated Rat Vascular Smooth Muscle Cells

Article

Author: Jepps, Thomas ; van der Horst, Jennifer

Understanding protein-protein interactions is crucial for unravelling subcellular protein distribution, contributing to our understanding of cellular organisation. Moreover, interaction studies can reveal insights into the mechanisms that cover protein trafficking within cells. Although various techniques such as Förster resonance energy transfer (FRET), co-immunoprecipitation, and fluorescence microscopy are commonly employed to detect protein interactions, their limitations have led to more advanced techniques such as the in situ proximity ligation assay (PLA) for spatial co-localisation analysis. The PLA technique, specifically employed in fixed cells and tissues, utilises species-specific secondary PLA probes linked to DNA oligonucleotides. When proteins are within 40 nm of each other, the DNA oligonucleotides on the probes interact, facilitating circular DNA formation through ligation. Rolling-circle amplification then produces DNA circles linked to the PLA probe. Fluorescently labelled oligonucleotides hybridise to the circles, generating detectable signals for precise co-localisation analysis. We employed PLA to examine the co-localisation of dynein with the Kv7.4 channel protein in isolated vascular smooth muscle cells from rat mesenteric arteries. This method enabled us to investigate whether Kv7.4 channels interact with dynein, thereby providing evidence of their retrograde transport by the microtubule network. Our findings illustrate that PLA is a valuable tool for studying potential novel protein interactions with dynein, and the quantifiable approach offers insights into whether these interactions are changed in disease.

News (Medical) associated with Kv7.4

09 Jan 2024

·www.prnewswire.com

Acousia Therapeutics attracts new investor on its path to make hearing loss a treatable disease

German pioneer biotech accelerates hearing loss solution development with fresh capital boost TÜBINGEN, Germany, Jan. 9, 2024 /PRNewswire/ -- Acousia Therapeutics GmbH, a clinical-stage biotech company developing drug candidates against acute and chronic forms of hearing loss, proudly announces Esperante Ventures as the latest addition to its esteemed group of investors. The infusion of fresh capital is set to boost the progress of Acousia's Kv7.4 activator programs, with a focus on advancing the ongoing clinical development of ACOU085. ACOU085 is a proprietary, small-molecule, etiology-agnostic otoprotective drug candidate, which recently entered Phase 2 clinical testing for the prevention of chemotherapy-induced hearing loss and sensory hair cell death in cancer patients. The significant otoprotective potential of ACOU085 is broadly supported by results from a number of preclinical studies in relevant models. Sustained target exposure by ACOU085 in the cochlea is achieved through local application of a novel, proprietary slow-release gel formulation using standard transtympanic injection. Tim Boelke, CEO of Acousia Therapeutics, said, "Adding Esperante Ventures with their existing position in inner ear therapeutics to our investor syndicate – amidst a challenging macro-economic environment and despite recent drawbacks in competing hearing loss drug development programs – is a testament to the confidence in our unique and proprietary Kv7.4 activator approach. Our lead candidate ACOU085, currently in Clinical Phase 2, aims to set a new standard for treating acute and subacute forms of hearing loss." Dean Slagel, Managing Director of Esperante Ventures, said "We are excited to invest in Acousia's novel and compelling approach to treating the significant unmet indication of chemotherapy-induced hearing loss, supported by its excellent leadership, robust data and experienced investors." About Acousia Therapeutics GmbH Acousia Therapeutics GmbH is a privately held, clinical-stage biotech company based in Tübingen, Germany. The company is dedicated to the identification of small molecules for the effective prevention and treatment of different hearing loss etiologies. Acousia is focused on the development of proprietary drug candidates, which are designed to affect the sensory outer hair cells (OHC) in the cochlea of the inner ear. The unique dual mode of action of its small-molecule Kv7.4 activators combines acute functional OHC enhancement and sustained OHC protection aim to both enhance and preserve a patient's natural hearing. Acousia Therapeutics develops drugs for both local and systemic administration. Contact Tim Boelke, M.D. [email protected] About Esperante Ventures Esperante is a corporate venture capital company and part of a family-controlled global life science group. Its leadership is experienced in the management of life science companies with an emphasis on the development and commercialisation of prescription pharmaceuticals. Its investment focus is mainly from Phase 2 clinical development onwards with a geographical focus in Europe and North America. Further information is available at

Phase 2

09 Oct 2023

·pipelinereview.com

Hearing Loss Company Acousia Therapeutics Green Lighted for Game-Changing Phase

TÜBINGEN, Germany I October 9, 2023 I Acousia Therapeutics, a pioneer clinical-stage biotech company focused on the development of novel drug therapies for the prevention and treatment of acute and chronic forms of hearing loss, received approval from the German regulatory authorities (BfArM) for its groundbreaking Phase 2 clinical trial of the etiology-agnostic otoprotectant ACOU085 in patients with cisplatin-induced hearing loss. Cisplatin-based chemotherapy, a lifeline for countless cancer patients, often delivers an unwanted side effect: irreversible hearing loss, i.e. ototoxicity, which occurs in 60% or more of cancer survivors. This makes the prevention of cisplatin-induced ototoxicity a significant unmet medical need for patients with a large potential market for a new therapeutic regimen. In a recently concluded Phase 1b clinical trial, ACOU085 demonstrated excellent safety and tolerability as well as long local residence time of the proprietary, sustained-release formulation, which is essential for providing extended otoprotection in acute hearing loss conditions such as cisplatin-induced ototoxicity. The Phase 2a multicentric, randomized, placebo-controlled, split-body trial will evaluate the efficacy of ACOU085 for preventing cisplatin-induced ototoxicity in young male patients diagnosed with testicular cancer. The clinical study will assess several efficacy outcomes for ACOU085, including changes in high-frequency, pure-tone audiometry, speech comprehension in quiet and noisy environments, and otoacoustic emissions. The enrolment of the first patients is expected in late 2023. Tim Boelke, CEO and Chief Medical Officer of Acousia, said: "Cisplatin is a lifeline for cancer patients, yet the heartache of hearing loss it brings is devastating. We are thrilled by the swift regulatory approval of our ACOU085 trial, which validates our development approach and offers the promise of hearing protection as patients battle cancer. " About Acousia Therapeutics GmbH Acousia Therapeutics GmbH is a privately held, clinical-stage biotech company based in Tübingen, Germany. The company is dedicated to the identification of small molecules for the effective prevention and treatment of different hearing loss etiologies. Acousia is focused on the development of proprietary drug candidates, which are designed to affect the sensory outer hair cells (OHC) in the cochlea of the inner ear. For example, the unique dual mode of action of its small-molecule Kv7.4 agonists, the acute functional OHC enhancement, and the sustained OHC protection aim to both enhance and preserve a patient's natural hearing. Acousia Therapeutics develops drugs for both local and systemic administration. SOURCE: Acousia Therapeutics

Phase 2Phase 1Clinical Result

09 Oct 2023

·www.prnewswire.com

Hearing Loss Company Acousia Therapeutics Green Lighted for Game-Changing Phase 2 Trial

TÜBINGEN, Germany, Oct. 9, 2023 /PRNewswire/ -- Acousia Therapeutics, a pioneer clinical-stage biotech company focused on the development of novel drug therapies for the prevention and treatment of acute and chronic forms of hearing loss, received approval from the German regulatory authorities (BfArM) for its groundbreaking Phase 2 clinical trial of the etiology-agnostic otoprotectant ACOU085 in patients with cisplatin-induced hearing loss. Cisplatin-based chemotherapy, a lifeline for countless cancer patients, often delivers an unwanted side effect: irreversible hearing loss, i.e. ototoxicity, which occurs in 60% or more of cancer survivors. This makes the prevention of cisplatin-induced ototoxicity a significant unmet medical need for patients with a large potential market for a new therapeutic regimen. In a recently concluded Phase 1b clinical trial, ACOU085 demonstrated excellent safety and tolerability as well as long local residence time of the proprietary, sustained-release formulation, which is essential for providing extended otoprotection in acute hearing loss conditions such as cisplatin-induced ototoxicity. The Phase 2a multicentric, randomized, placebo-controlled, split-body trial will evaluate the efficacy of ACOU085 for preventing cisplatin-induced ototoxicity in young male patients diagnosed with testicular cancer. The clinical study will assess several efficacy outcomes for ACOU085, including changes in high-frequency, pure-tone audiometry, speech comprehension in quiet and noisy environments, and otoacoustic emissions. The enrolment of the first patients is expected in late 2023. Tim Boelke, CEO and Chief Medical Officer of Acousia, said: "Cisplatin is a lifeline for cancer patients, yet the heartache of hearing loss it brings is devastating. We are thrilled by the swift regulatory approval of our ACOU085 trial, which validates our development approach and offers the promise of hearing protection as patients battle cancer." About Acousia Therapeutics GmbH Acousia Therapeutics GmbH is a privately held, clinical-stage biotech company based in Tübingen, Germany. The company is dedicated to the identification of small molecules for the effective prevention and treatment of different hearing loss etiologies. Acousia is focused on the development of proprietary drug candidates, which are designed to affect the sensory outer hair cells (OHC) in the cochlea of the inner ear. For example, the unique dual mode of action of its small-molecule Kv7.4 agonists, the acute functional OHC enhancement, and the sustained OHC protection aim to both enhance and preserve a patient's natural hearing. Acousia Therapeutics develops drugs for both local and systemic administration. Contact: Tim Boelke, M.D. [email protected] SOURCE Acousia Therapeutics GmbH

Phase 2Clinical ResultPhase 1

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Kv7.4

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