SeSAME syndrome is a rare disorder that impacts the central nervous system, the inner ear, and the kidneys. It is associated with mutations of the KCNJ10 gene, which encodes the inward rectifier potassium channel, Kir4.1. Protheragen offers a unique integrated research and drug development platform for rare kidney diseases such as SeSAME syndrome, enabling us to provide comprehensive services from developing diagnostics and modeling the disease to optimizing preclinical and therapeutic agents.
Overview of SeSAME Syndrome
SeSAME syndrome is an extremely rare condition, occurring in 1 in 1,000,000 people. It is characterized by an imbalance of electrolytes in the body, seizures, sensorineural hearing loss, ataxia, and intellectual retardation, and is diagnosed within the family as an autosomal recessive syndrome. Individuals suffering from SeSAME syndrome have renal insufficiency, which is characterized by the loss of electrolytes such as Na+, K+, and Mg2+, the activation of the renin-angiotensin-aldosterone system, and hypokalemic metabolic alkalosis.
Fig.1 Hypokalemia in SeSAME syndrome. (Lo, J.,
et al., 2022)
Pathogenesis of SeSAME Syndrome
The disorder emerges due to alterations in the KCNJ10 gene, which is responsible for the inwardly rectifying potassium channel, Kir4.1. The Kir4.1 channel is overexpressed in the affected tissues, which include the CNS, inner ear, and kidney. The impaired function of Kir4.1 alters potassium homeostasis in these tissues, which is responsible for the different features found in EAST/SeSAME syndrome. More specifically, in the renal, Kir4.1 is found in the basolateral membrane of the renal distal convoluted tubule, and its loss of function leads to renal features of Gitelman syndrome with hypokalemic alkalosis, low levels of calcium in urine, and hypomagnesemia.
Fig.2 Localization of human Kir4.1 mutations. (Lo, J.,
et al., 2022)
Therapeutics Development for SeSAME Syndrome
Because SeSAME syndrome is so rare, therapy options are still being developed, concentrating mainly on providing care and symptom management. Treating each individual's individual symptoms provides antiepileptic medications for seizures, electrolytes (potassium and magnesium) for tubulopathy, and ataxia, as well as hearing loss requires supportive therapies. Research is investigating some small-molecule drugs as potential therapy strategies for the malfunctioning Kir4.1 potassium channel or gene therapy aimed at functional channel restoration.
Our Services
Support and research for SeSAME syndrome, including diagnostics development like biomarker assays, therapeutics development, disease model development, as well as preclinical services such as pharmacokinetics, pharmacodynamics, and safety evaluation, are all provided through the advanced technologies offered by Protheragen.
Therapeutic Development Platforms for SeSAME Syndrome
Disease Models Development for SeSAME Syndrome
Disease models play a pivotal role in discovering new drug targets, confirming therapy effectiveness, and evaluating toxicity in a human-relevant way. Our platform for disease model development harnesses the latest technologies for the creation of physiologically relevant models of SeSAME syndrome, allowing for mechanistic study and drug screening. We provide bespoke models at the cellular, organoid, and animal levels, which recapitulate the disease's genetic and functional features.
Cell-based & Organoid Models
- Patient-derived cell model
- KCNJ10-knockout cell line model
- Induced pluripotent stem cells (iPSCs)
- iPSCs-derived kidney organoids
- And more
Animal Models
SeSAME syndrome animal models are genetically modified organisms with a defective Kcnj10 gene that mimic the human disease.
- Kcnj10 knockout model
- And more
Drug Pharmacokinetics & Safety Evaluation Services
In Vitro ADME Services
- Renal Clearance Assay
- Drug-Transporter Interaction Screening
- Metabolic Stability Assay
- CYP Inhibition Screening
- Plasma Protein Binding
Protheragen's unique advantages relevant to the SeSAME syndrome research stem from our integrated services platform and customized solutions. By focusing on scientific innovation coupled with rare diseases, we enable researchers and partners to transcend the hurdles of drug development for diseases like SeSAME syndrome. Get in touch for collaboration or service requests if you are interested.
Reference
- Lo, Jacky et al. "EAST/SeSAME Syndrome and Beyond: The Spectrum of Kir4.1- and Kir5.1-Associated Channelopathies." Frontiers in physiology 13 (2022): 852674.
All of our services and products are intended for preclinical research use
only and cannot be used to diagnose, treat or manage patients.
