Drug Discovery for Central Nervous System Channelopathies

Creative Bioarray is committed to helping clients develop drugs for the central nervous system (CNS) channelopathies, including epilepsy, cerebellar ataxias, and migraines. We focus on the discovery of ion channel modulators, opening the way for the development of personalized therapies with higher efficacy and fewer side effects.

Introduction

In recent years, with the high incidence of neurological diseases such as Alzheimer's disease, depression, schizophrenia, and Parkinson's disease, the development of CNS drugs has gradually become a hot field. It is well known that ion channels are abundant in the CNS. Aberrant expression of these ion channels often results in some CNS channelopathies, which overlap with important neurological diseases such as epilepsy, ataxia, and other neurodegenerative diseases. Therefore, characterizing more ion channel properties, structures, and functions and gaining insights into the role of ion channels in CNS physiology and pathology could help advance the diagnosis and treatment of many CNS channelopathies.

Fig. 1 The tentative roles of different ion channels implicated in epilepsy are indicated schematically, with gain and loss of function in red and blue, respectively. (Kullmann, 2010)

Drug Development for Epilepsy

Gain or loss of function mutations in ion channel genes are associated with epilepsy because different classes of ion channels play important roles in maintaining the balance between excitatory and inhibitory inputs in the brain. Several drugs, such as benzodiazepines, stiripentol, and Nav blockers, are available on the market to suppress the abnormal neuronal firing underlying epileptic seizures. However, due to adverse drug reactions, new and more effective treatment options need to be evaluated to meet the needs of personalized medicine.

We help clients develop anti-epileptic drugs by reducing neural hyperexcitability through different mechanisms.

Our services include but not limited to:

• Development of subtype-selective Na_v channel ligands with the advantages of improved safety and effectiveness.
• Development of pharmacological chaperones for folding defective mutants of Na_v, K_v, and ClC channels.
• Development of K_v openers with selectivity and safety advantages.

Drug Development for Cerebellar Ataxias and Migraine

It has been proved that multiple ion channels are involved in the pathological process of cerebellar ataxia and migraine, including K_v1.1 (KCNA1), Ca_v2.1 (CACNA1A), K_v3.3 (KCNC3), and K_v4.3 (KCND3). We help clients develop drugs to treat cerebellar ataxia and migraine by restoring cerebellar function and reducing the frequency, duration, and severity of attacks.

Our services include but not limited to:

• Development of SK channel openers to restore Purkinje cells pacemaking.
• Development of K_v1.1 dysinactivators.

With extensive experience in the field of drug development and advanced ion channel analysis platform, Creative Bioarray has made great progress in drug development of central nervous system diseases caused by channel dysfunction and has made contributions to the successful completion of many projects. If you are interested in our services, please contact us for more details.

Reference

1. Kullmann, D. M. Neurological channelopathies. Annual review of neuroscience, 2010, 33: 151-172.