Research ids neurological disease gene
epilepsy, which is associated with a movement disorder. The study
provides the first direct genetic evidence that the co-existence of
these conditions represents a new syndrome.
The discovery establishes a solid platform in which future research will seek to use the discovery to identify and develop new treatments for the movement disorder paroxysmal dyskinesia as well as epilepsy.
Epilepsy is a common and debilitating neurological disorder affecting more than 40 million people worldwide. It is caused by disruptions in the electrical signals of the brain, resulting in seizures.
Paroxysmal dyskinesia is also a neurological disorder. It is characterised by sudden, unpredictable, disabling attacks of involuntary movement. Typically, PD attacks do not result in a loss of consciousness, which often occurs with epilepsy.
"Epilepsy and movement disorders are distinct diseases, but increasingly they are found to affect the same patient or the same family," said Qing Wang, one of the study's lead investigators and director of the Centre for Cardiovascular Genetics
"The study is significant clinically because it raises awareness of coexistent epilepsy and PD as a distinct clinical entity," she added.
The study and its discoveries provides additional insight into the development of epilepsy and its research-neglected relation paroxysmal dyskinesia (PD).
The parameters of the study involved a genetic analysis of large, multi-generational family of mixed European descent. Sixteen family members were known to have epilepsy, PD or both conditions; four had epilepsy only; seven had PD only, and five suffered from both conditions.
Researchers from The Cleveland Clinic examined genetic markers on human chromosomes 1-22, and isolated a mutation in an ion channel gene, KCNMA1 (making the BK potassium channel) that causes epilepsy and PD. The mutation was found only in the 16 family members diagnosed with these conditions. In turn, more than 500 healthy individuals used as a control population in the study, none carried the mutation.
Ion channels play an important role in cell signalling, electrical excitability and fluid transport, and are drug targets themselves in a number of indications, including heart disease, diabetes, autoimmune diseases and migraine. Small molecules that block or open ion channels are considered to be promising drug candidates.
The study found that patients in the study have a hyperactive KCNMA1 gene. This means that a pharmaceutical agent that blocks the BK potassium channel may be effective in preventing epilepsy and PD in these patients.
"We believe that there is a strong likelihood that this discovery will yield important new products," said Christopher Coburn, executive director of CCF Innovations, the Clinic's technology transfer and commercialisation arm. "We look forward to engaging companies seeking to develop diagnostic and therapeutic neurological products and have filed patent protection to enable that exchange," he said.
With 300,000 people in the UK suffering from epilepsy (40 million people worldwide), the need for specialised but effective anti-epileptic drugs (AED) has never been more called for.
The binding site for current leading anti-epileptic drug Keppra (levetiracetam) has been isolated in the brain, specifically as a synaptic vesicle protein SV2A. This protein appears to play an important role in the release of neurotransmitters essential for the neuronal activity in the brain and spinal cord.
The identification of SV2A as the binding site for Keppra provides an innovative and unique drug discovery platform to identify new drugs with improved characteristics and provides molecular evidence that Keppra is different form all other anti-epileptic drugs. No other known anti-epileptic drugs (AED's) bind to SV2A.
SV2A, is the same binding site for another anti-epileptic drug levetiracetam, and is providing a target for future drug discovery at UCB Pharma. The company has filed two patent applications related to the discovery.
