Introducing research papers published in high-impact medical journals by members of the Epilepsy group at the Melbourne Brain Centre.
REAL-WORLD EFFICIENCY OF PHARMACOGENETIC SCREENING FOR CARBAMAZEPINE-INDUCED SEVERE CUTANEOUS ADVERSE REACTIONS
Zhibin Chen, Ph.D.
Carbamazepine is an often-prescribed first line treatment for epilepsy. In rare cases, it can induce severe and sometimes fatal skin reactions known as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). A particular form of a gene involved in the immune system, HLA-B*1502, is known to be strongly associated with the development of carbamazepine-induced SJS and TEN. Therefore, our investigators proposed genetic screening of epilepsy patients as a means of preventing SJS and TEN.
Our researchers conducted a trial of HLA gene screening in epilepsy patients to determine the effectiveness and cost-efficiency of screening for HLA-B*1502 to prevent SJS and TEN. The trial data was compared to similar genetic screening used processes for some types of cancers e.g. mammography and Pap smear. Our researchers found that the genetic testing was very effective at preventing SJS and TEN in epilepsy patients. However, implementing a screening program using in-hospital or external laboratories was a cost prohibitive model. To overcome this, our researchers recommended, and have already begun planning, a low-cost, pocket-size gene testing device that can be used at the point-of-care (“on the spot”) to genetically screen epilepsy patients before choosing medication. Our current and future work will focus on validating this technology and conducting field trials.
SODIUM SELENATE REDUCES HYPERPHOSPHORYLATED TAU AND IMPROVES OUTCOMES AFTER TRAUMATIC BRAIN INJURY
Dr Sandy Shultz
A protein known as “hyperphosphorylated tau” (basically, overly active Tau) has been implicated as a major driver of different forms of epilepsy and as a secondary cause of problems in Traumatic Brain Injury (TBI).
Hyperphosphorylated tau can be switched off by another protein (PP2A/PR55). PP2A/PR55 is decreased following TBI. Therefore, our investigators focused on reactivating PP2A/PR55 so it could do its job: switching off hyperphosphorylated tau.
Sodium selenate is a drug known to inhibit epileptic seizures. Our research examined whether sodium selenate could increase the activity of PP2A/PR55 in rats with TBI. More PP2A/PR55 would mean less hyperphosphorylated tau, reduced severity of TBI and reduced seizures.
Our research showed that rats with TBI who received continuous sodium selenate treatment displayed reduced brain damage and improved behavioural outcomes. This was associated with a decrease in the amount of hyperphosphorylated tau. Our findings suggest that sodium selenate might be a useful therapy to improve the long-term outcomes for people following traumatic brain injury.