Cause and Possible Treatment for Hereditary Disorder -- MEDICA Trade Fair

The research focused on a type of ataxia called episodic ataxia type-2. It results from gene mutations that affect calcium channels, which are involved in releasing neurotransmitters in the brain and regulating excitability in neurons. Episodic ataxia type-2 was thought to be due to impaired transmission of neurotransmitters, but the scientists suspected that something else was going on.

They studied specialized cells in the brain's cerebellum called Purkinje cells, which are rich in calcium channels. Purkinje cells help coordinate movement by acting as information clearinghouses: They take in sensory and other inputs relayed to them by more than 150,000 excitatory and inhibitory synaptic inputs, combine them with the cell's own intrinsic activity or "pacemaking," and then send out the signals necessary for motor coordination.

The researchers investigated whether ataxia might be due to a reduction in the precision of the intrinsic pacemaking by Purkinje cells. Studying a number of mouse models of ataxia type-2, they found a gene-dependent loss of the precision of pacemaking in Purkinje cells, which prevented them from accurately accounting for the strength and timing of synaptic inputs when sending out signals directing muscle movement.

This loss of pacemaking precision was traced to reduced activity of calcium-activated potassium channels in Purkinje cells – a direct consequence of the reduced activity of calcium channels in these disorders. The researchers were able to remedy this problem with a drug called 1-ethyl-2-benzimidazolinone (EBIO). When EBIO was infused into the brains of ataxic mice, the mice's motor coordination improved significantly.; Source: Albert Einstein College of Medicine