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KK Women’s and Children’s Hospital (KKH) clinician scientists, Associate Professor Derrick Chan and Dr Lee Jan Hau were amongst more than 50 researchers honoured at the National Medical Research Council (NMRC) Awards in 2020 for their contributions toward improving clinical outcomes and quality of life for children.

“Close collaboration and support from the NMRC and fellow research institutes are keystones for the advancement of research into some of the most critical health concerns for children,” says Assoc Prof Derrick Chan, Director, KK Research Centre, KKH, who received the NMRC Clinician Scientist Award (Investigator Category), 2019 grant cycle.

“Much remains unknown about the genesis of childhood conditions, such as epilepsy. Deepening our understanding of the complex mechanisms of diseases helps to build a foundation for the discovery and development of targeted therapies for our patients,” adds Assoc Prof Chan, who is also Head and Senior Consultant, Neurology Service, KKH, and Deputy Director, SingHealth Medical Technology Office.

Elucidating the role of inflammation in childhood epileptogenesis

Epilepsy, defined as recurrent unprovoked seizures, is a common neurological diagnosis with 50 million cases in the world. The condition ranges from epilepsy with rare seizures, to severe epilepsy with frequent seizures and severe developmental or functional impact.

Conventional treatments for epilepsy are untargeted and short-term. In one third of cases, epilepsy is refractory, persisting despite first line treatment.

“Ideally, treatment should target epileptogenesis, which is the underlying process that creates and perpetuates epilepsy and leads to refractory epilepsy. There is an urgent unmet need to deepen our understanding of the mechanisms in epileptogenesis and subsequent disease progression,” shares Assoc Prof Chan.

“T helper 17 (Th17) and CX3CR1+ Natural Killer (NK) cells play key roles in mediating immune responses. Our pilot work shows increased Th17 and CX3CR1+ NK cell-mediated proinflammatory processes in patients with refractory epilepsy. We hypothesise that immune dysregulation drives epileptogenesis through peripheral and CNS immune derangement, and that Th17 and CX3CR1+ NK mediated pro-inflammatory changes are two significant contributors to epileptogenesis, persistence of epilepsy and refractory epilepsy in childhood,” says Assoc Prof Chan.

With increasing evidence for a key role of inflammation in the brain, seizures and epilepsy, Assoc Prof Chan is leading a team to elucidate the role of inflammation in epileptogenesis and refractory seizures in greater detail.

“With this knowledge, we hope to develop clinical treatments to reduce the evolution to epilepsy, reduce clinical seizure severity and prevent the development of refractory epilepsy.”

Improving outcomes in critically ill children through protein supplementation

Dr Lee Jan Hau, Senior Consultant, Children’s Intensive Care Unit, KKH is looking toward a personalised nutritional approach to improving clinical outcomes in critically ill children who require intensive care.

Winner of a NMRC Transition Award for the 2019 grant cycle, Dr Lee is opening a two-centre randomised controlled trial (RCT) on the benefits of protein supplementation for critically ill children who present with malnutrition on admission to a paediatric ICU (PICU).

“Up to 40 per cent of critically ill children admitted to PICUs exhibit malnutrition. Low protein intake is associated with worse clinical course and outcomes in these children. It can potentially lead to the loss of lean body mass with muscle wasting and, subsequently, functional disability, delayed weaning from mechanical ventilation, prolonged hospital stay and increased mortality,” shares Dr Lee.

“Nutrition support is one of the main components of daily management of any critically ill patient, and our team aims to study the effects of protein supplementation in the PICU on changes in the patient’s muscle size, length of hospital and PICU stay, and the duration of mechanical ventilation.”

To date, there has been no RCT in this regard for critically ill children, highlighting significant gaps in the knowledge of nutrition supply in PICUs. However, a retrospective study in 107 children with acute respiratory distress syndrome published in 2017 by Dr Lee and team established that survivors received significantly more protein compared to non-survivors. Those who did not received sufficient protein had a longer length of hospital stay.

“The results from this pilot study will inform a future large-scale regional confirmatory study of protein supplementation in critically ill children in Asia, under the Paediatric Acute & Critical Care Medicine Asian Network (PACCMAN),” adds Dr Lee.

“Our long-term goal is to identify targeted therapies to reduce childhood morbidity after recovery from a critical illness,” shares Dr Lee. “By bridging the knowledge gap in the effects of protein supplementation in this vulnerable group of patients, we can help to pave the way for a personalised approach towards nutritional prescription to advance care in the PICU and enhance patient outcomes.”