Grant funding success for CBR researchers

Scientists at the Centre for Brain Research have been awarded almost $500,000 for four new research projects. The funding comes from the Auckland Medical Research Foundation and the Neurological Foundation of New Zealand.

The studies will examine the underlying biology of brain disorders including autism and neurodegenerative disease. Potential new treatments being developed include stem cell research on induced neural precursor cells, and a clinical trials system called EpiNet.

 INDUCED NEURAL PRECURSOR CELLS ($144,023 – 2 YEARS)
Dr Bronwen Connor, Dr Christof Maucksch, Dr Mirella Dottori, A/Prof Cris Print,  Dept of Pharmacology, The University of Auckland. Funded by Auckland Medical Research Foundation.

It has long been considered that once a cell reaches maturity it is unable to change to a different cell type. However, recent advances in stem cell biology have shown that mature cells, such as skin cells, can be transformed back to an “embryonic-like” stem cell state where cells exhibit pluripotency (the ability to become any cell type) by the forced expression of specific genes (reprogramming). Advancing this capability, we propose it is possible to convert one cell type to another directly, without the need to first revert the cell to a pluripotent stem cell state. This project aims to establish an innovative approach for generating immature brain cells (neural precursor cells) directly from adult human skin. Of major significance is that this will avoid the need to generate an intermediate embryonic stem cell phase, providing neural precursor cells for research and therapeutic applications without risk of tumour formation from pluripotent stem cell contamination. This project will establish cell reprogramming as a key capability in New Zealand. The ability to directly generate human neural precursor cells offers a powerful system for studying brain development, modeling neurological disease, drug discovery and eventually, cell replacement therapy.

THE SYNAPTIC BASIS OF AUTISM ($136,351 – 1 YEAR)
Co-funded by Auckland Medical Research Foundation and the Neurological Foundation
Dr Johanna Montgomery, Prof Craig Garner, Dept of Physiology & Centre for Brain Research, The University of Auckland.

Autism Spectrum Disorders are complex disorders that are diagnosed based on behavioural symptoms including social and cognitive impairments, communication difficulties and repetitive behaviours. Interestingly, many of the genes that have been implicated in Autism encode proteins found at excitatory synapses in the brain. In this research proposal we will form an international collaborative research effort to test the hypothesis that the Autism-associated mutations in these synaptic proteins disrupt the function of synapses. Using electrophysiology recordings as a measure of synapse function, we will compare how proteins that are associated with Autism can alter synapses in the hippocampus, the part of the brain critical for cognitive functions such as learning and memory. We will also begin to determine the mechanisms underlying how these changes occur. These experiments have the potential to determine how the formation, plasticity and maturation of excitatory synapses may be disrupted in Autism, leading to interference with cognitive function and behaviour.

CB2 IN THE BRAIN ($74,457 – 1 YEAR)
Prof Michelle Glass, Dr Scott Graham, Dept of Pharmacology & Clinical Pharmacology, The University of Auckland. Funded by Auckland Medical Research Foundation.

Cannabinoid CB2 receptors have been suggested to be an appealing target for neuroinflammatory disorders as many believe them to be found only on immune cells. However, their distribution is actually highly controversial with some groups reporting wide spread neuronal distribution, while others see little evidence for CB2 in the brain. Part of the reason for these discrepancies are that the antibodies used to detect this protein are not entirely specific. Furthermore, many of the assumptions about CB2 expression in the brain are based on animal studies and may not represent the situation in the human brain. As many drug companies are aiming to bring CB2 directed therapies onto the market it is critical that the localisation of the receptor be accurately determined. This study aims to optimise a sensitive method which will allow for the determination of CB2 gene expression in the normal healthy human brain.

VALIDATION OF THE EpiNet PLATFORM AND THE EpiNet STUDY GROUP

Dr Peter Bergin, Auckland City Hospital, Auckland ($85,464)

Funded by the Neurological Foundation.

In the July 2009 grant round, the Neurological Foundation approved funding for Dr Peter Bergin’s international collaborative pilot study which set up an internet-based platform to recruit patients for epilepsy drug trials. The platform, called EpiNet, is now functioning and is able to be accessed by adult and paediatric neurologists from anywhere in the world. In this second study phase, the EpiNet study group, led by Dr Bergin and involving an international collaboration of epileptologists, will undertake a study to validate both the EpiNet study group and the EpiNet platform before undertaking clinical trials. The group will circulate 50 fictitious case histories to doctors who have expressed interest in participating in the EpiNet project, and ask them to enter details into the EpiNet database, using standard and internationally approved epilepsy classification systems. Investigators’ results will be compared. As well as confirming that investigators ‘speak the same language’ globally, the study will also determine how much variability there is when classifying individual cases using the classification schemes. At the same time, the group will undertake steps to confirm that the database and systems procedures are robust.