Tomorrow's Health, Today's Research

Kerry Delaney

Professor, Biology Department
Member of the International Collaboration on Repair Discoveries (ICORD)
Member of UVic’s CanAssist assistive technologies group
Investigator, CIHR Synaptic Function and Plasticity Group Grant
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Phone: (250) 472-5657
Department Page
Research area: neurophysiology
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Research Profile

Two pronged attack on Rett syndrome

Neurophysiologist Dr. Kerry Delaney has two strategies to tackle Rett syndrome: gene therapy and vagus nerve stimulation.

Rett syndrome is a neural developmental disorder that occurs exclusively in girls. Babies with Rett syndrome appear to develop normally for six to 18 months. Then, tragically, they enter a period of regression, ending up with severe motor and cognitive deficits as children and adults.

Normally the brains of babies at this age undergo rapid neuron growth and maturation, but this doesn’t happen in girls with Rett syndrome. Their neurons fail to grow and make new connections, or even maintain existing connections. While at first glance their neurons look physiologically normal, says Delaney, when you look closer, their neurons are actually stunted with shorter branches and fewer sites for connection with other neurons.

Delaney is an expert in two-photon microscopy, which allows him to see the structure of the neurons in living tissue. This expertise makes him a natural addition to a gene therapy collaboration with CBR member Dr. Patrick MacLeod, and former CBR member Dr. David Levin, now at the University of Manitoba.

Gene therapy is a technique that involves inserting a good copy of a gene into a chromosome to compensate for a mutated or missing gene, which in the case of Rett syndrome, is a mutation in the MECP2 gene.

In order to test a gene delivery system, the collaborators have developed a strain of mice missing MECP2, giving these mice Rett syndrome. The mice also expresses Yellow Fluorescent Protein in a subset of cortical neurons which will cause these neurons to fluoresce under a two-photon microscope, allowing Delaney and his team to visualize the structure and connections of these cortical neurons. Delaney will study the brains of the mice before and after gene delivery experiments to monitor the effect of the introduced gene.

Meanwhile, Delaney is tackling Rett syndrome from another angle: he is exploring the idea of using a treatment called vagus nerve stimulation in early postnatal development to encourage nerve growth. He is working with UVic’s CanAssist team, a group of researchers and students who develop devices to help those with special needs.

Vagus nerve stimulation is already used as a treatment for severe epilepsy (including epilepsy that is a secondary symptom of Rett syndrome). It involves implanting a device the size of a looney under the skin of the chest, which delivers short bursts of electrical energy to the brain via the vagus nerve, interrupting seizures. (The vagus nerve runs from the brainstem through the neck into the chest and abdomen and is responsible for controlling heart rate, digestion and other autonomic body functions.)

Delaney’s idea comes from anecdotal stories from doctors that when they treat Rett syndrome seizures with vagus nerve stimulation, physical and mental development seems to improve. That could be because vagus nerve stimulation suppresses epilepsy by releasing neuromodulatory substances in the cortex, and it’s known that neuromodulators also help neurons form long lasting connections. So far, the treatment is used to treat seizures in older girls, but Delaney theorizes that treating infants with vagal nerve stimulation could help them form the neural connections they need to develop. He is testing his theory in mice.

To do this, first he had to build a vagal nerve stimulator small enough to be implanted in a mouse, which has turned out to be no mean feat. Delaney and the CanAssist team are building a stimulator about the size of a pea, which contains no battery and is powered by inductive currents. It can also record brain wave activity and transmit this information using a two-way radio to a computer for display and analysis. Next his team will place the device in mice with Rett syndrome to begin trials to see if the progress of the disease can be alleviated in mice.

Expert in two photon microscopy

The theory behind a two-photon microscope has been around since the ‘30s, but the microscopes themselves are still not common, partly because of the expense of the high intensity pulsed lasers that are needed. The technique is powerful because it allows researchers to view florescent markers in sharp focus up to several hundred micrometers below the surface of living tissue, something that is not possible with other types of microscopy. With two-photon microscopy, Delaney and his team can see the full structure of a neuron as it grows during development, or measure calcium ion influx into the small branches of neurons when they are electrically active and signalling each other.

Delaney and his colleague Tim Murphy at University of British Columbia were the first researchers to have a two-photon microscope configured for electrophysiological research in Canada, thanks in part to Delaney’s ability to modify existing technology for his own purposes.

Now he and his collaborators at UBC have eight two-photon microscopes (six home-made), giving them a unique ability to look at neuron physiology and morphology. Six labs, with about 50 trainees, were awarded a Canadian Institutes for Health Research group grant for Synaptic Function and Plasticity, making them a major centre for nervous system study in Canada.

When Delaney is not working on Rett syndrome, he uses two-photon microscopy (among other techniques) to study the control of calcium ions and calcium channels in neurons. More...