SK-NEURON

In the proposed research project Cerebrum DAO aims to build upon and translate the work of Dr. Miao Zhang, Dr. Keykavous Parang (Chapman University) and Dr. Ilya Bezprozvanny (ex-UT Southwestern Medical Centre). Cerebrum DAO is taking the single lead in the project, based on the cooperation with Chapman University and Cerebrum DAO Partners. The proposed project aims to address an unmet medical need for the treatment of Spinocerebellar Ataxias (SCAs) and extend to related tremor disorders (essential tremor [ET]), by developing a novel molecule class, patent pending by the Chapman University CA. Currently no cures or treatments exist for SCAs.

Recently dysfunction of small conductance calcium-activated potassium (KCa2, SK) ion channels has been linked to several neurological disorders. The characteristics of these ion channels and their expression in Purkinje cells (PCs) has led to the hypothesis that they could be suitable drug targets to treat SCAs. A SCA2 mouse model showed improved motor performance after treatment with SK channel modulators and one KCa2.2/2,3 selective channel modulator has entered clinical trials. The specific expression of the KCa2.2 ion channel in the cerebellum and the side effects primarily attributed to the KCa2.3 ion channel led to the search for a KCa2.2 selective allosteric modulator.

This project aims to replicate the original findings and further design, test and develop KCa2.2 selective allosteric modulator leads to a preclinical candidate. Based on the preclinical research by the groups of UT Southwestern, Northeastern University, and Chapman University, this modulation leads to normalizing of the firing pattern in vitro and behavioural improvements in the SCA2 mouse model.