Coffin-Lowry Syndrome (CLS)
Coffin-Lowry syndrome (CLS) is an uncommon hereditary condition which results from changes to the RPS6KA3 gene on the X chromosome. At Protheragen, we work on designing innovative treatments and creating precise animal models for CLS that speed up the preclinical stages of prospective therapies. Our experience enables us to safeguard that the client's project receives the best and most timely backup, which in turn streamlines drug development processes.
Overview of Coffin-Lowry Syndrome (CLS)
Coffin-Lowry syndrome (CLS) is a rare disorder that lies along the spectrum of X-linked dominant neurodevelopmental illnesses. CLS is caused by mutations within the RPS6KA3 gene which is responsible for encoding one of the ribosomal proteins–S6 kinase alpha-3 (RSK2). CLS is estimated to occur in 1 in every 40,000–50,000 individuals, and is more common in men than women. CLS is marked by severe symptoms in males, while female carriers exhibit milder symptoms.
Fig.1 The proposed pathway of RSK related genes. (Lv Y, et al., 2019)
Pathogenesis of Coffin-Lowry Syndrome (CLS)
The pathogenesis of Coffin-Lowry syndrome (CLS) is primarily caused by loss-of-function mutations in the RPS6KA3 gene located at Xp22.12, which encodes the ribosomal S6 kinase 2 (RSK2) protein. As a key regulator of the MAPK/ERK-CREB signaling pathway, RSK2 deficiency disrupts critical neurodevelopmental processes including synaptic plasticity, neuronal survival, and CREB-mediated gene transcription.
Fig.2 The RSK signaling pathway. (Marques Pereira P, et al., 2010)
Therapeutic Development for Coffin-Lowry Syndrome (CLS)
| Drug Names | Mechanism of Action | Targets | Research Phase |
| Clonazepam | Clonazepam enhances the effect of the neurotransmitter GABA at the GABA-A receptor, producing sedative, anxiolytic, and anticonvulsant effects. | GABA-A receptor | Approved |
| Valproate | Valproate increases levels of GABA in the brain by inhibiting its degradation and may modulate sodium channels, stabilizing neuronal activity. | GABA transaminase, Sodium channels | Approved |
| Fluoxetine | Fluoxetine selectively inhibits the reuptake of serotonin in the brain, enhancing serotonergic neurotransmission and improving mood and anxiety. | Serotonin transporter (SERT) | Approved |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
As a leader in rare neurodevelopmental disorder research, Protheragen offers comprehensive preclinical services to advance Coffin-Lowry syndrome (CLS) therapeutics from discovery to validation. Our specialized platforms integrate genetic analysis and disease-specific modeling to replicate disease pathology with high fidelity. Using advanced blood-brain barrier (BBB) models, we optimize central nervous system (CNS) drug delivery while evaluating neuroprotection and off-target effects.
Therapeutic Development Services
By Mechanism of Action
Disease Model Development Services
In Vitro Model Development
- RSK2 Knockout Mice: Recapitulating neurodevelopmental defects and skeletal abnormalities in CLS.
- D-RSK Mutant Drosophila flies: For studying the conserved RSK2 signaling pathway in synaptic plasticity and behavior.
Specializing in comprehensive preclinical assessment, Protheragen offers professional pharmacodynamic (PD), pharmacokinetic (PK) and toxicology research services to accelerate the therapeutic development of Coffin-Lowry syndrome (CLS).If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
References
- Lv Y, Zhu L, Zheng J, et al. Growth concerns in coffin–lowry syndrome: a case report and literature review[J]. Frontiers in Pediatrics, 2019, 6: 430.
- Marques Pereira P, Schneider A, Pannetier S, et al. Coffin–Lowry syndrome[J]. European Journal of Human Genetics, 2010, 18(6): 627-633.