Eliana is a two-year-old from Canada with a de novo mutation (V434L) in her KCNC1 gene which encodes for the Kv3.1 channel in central nervous system neurons such as cerebellar neurons and GABAergic interneurons. The mutation manifests as a variety of neurological disorders which can include myoclonic epilepsy and ataxia due to K+ channel mutation, developmental epileptic encephalopathy (DEE), or hypotonia, depending on the specific variant. Although Eliana does not exhibit typical DEE, she suffers from hypotonia, cortical-visual impairment, vertical nystagmus, and global delays.

Choi, Dongchana; Goodwin, Georgea; Stevens, Edward B.b; Soliman, Nadiac; Namer, Barbarad,e; Denk, Franziskaa,* (2023) PAIN

DOI: 10.1097/j.pain.0000000000003115

The endo-lysosomal system is a series of intracellular organelles responsible for recycling and degradation of macromolecules. Endo-lysosomes express several functionally diverse ion channels, crucial for regulating organelle trafficking and intracellular signalling as well as maintaining the acidic luminal pH for optimal enzymatic activity. Dysfunctions within the endo-lysosomal system are associated with multiple disorders including lysosomal storage disorders and neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. Lysosomal ion channels have therefore gained significant attention as potential targets for novel therapeutics.

Lysosomes are a critical component of eukaryotic cells, playing a role in degradation and recycling processes, signal transduction and extracellular secretion(I). Ion channels expressed on the endo-lysosomal membrane are crucial in intracellular signalling and maintaining the acidic luminal pH for optimal hydrolase activity(II). There are a number metabolic disorders, known as lysosomal storage diseases, that arise from lysosomal dysfunction(III).

Nace Zidar a., Tihomir Tomaˇsiˇc., Danijel Kikelj., Martina Durcik., Jan Tytgat., Steve Peigneur., Marc Rogers., Alexander Haworth., and Robert W. Kirby. (2023) New aryl and acylsulfonamides as state-dependent inhibitors of Nav1.3 voltage-gated sodium channel. European Journal of Medicinal Chemistry, 2023.

Yusheng Qu., Robert Kirby., Richard Davies., Ayesha Jinat., Stefano Stabilini., Bin Wu., Longchuan Yu., BaoXi Gao., and Hugo M. Vargas. (2023). Time Is a Critical Factor When Evaluating Oligonucleotide Therapeutics in Human Ether-a-Go-Go-Related Gene Assays. Nucleic Acid Therapeutics. Nucleic Acid Therapeutics, 2022.

The dF508 mutation represents the most common cause underlying cystic fibrosis. The resultant misfolding of the nascent cystic fibrosis transmembrane regulator (CFTR) protein and its subsequent proteasomal degradation lead to a deficiency in functional CFTR channels and Cl- efflux at the apical cell membrane in ducts throughout the body (Veit et al. 2016).

Here we share a short video introducing Metrion’s expanded high throughput screening capabilities. To learn more, or to request a quote, please email info@metrionbiosciences.com

The development of Automated Patch Clamp (APC) technology over the last 20 years has
transformed the research and development process for identifying novel drugs for ion channel targets.

Here we share a short video introducing Metrion’s extensive suite of cardiac safety screening services. To learn more, or to request a quote, please email info@metrionbiosciences.com