Inside the Lab- with Kerry Delaney
By Dr. Dominique Pichard, CSO, International Rett Syndrome Foundation (IRSF)
Dr. Kerry Delaney’s research on how the brain works in Rett syndrome is reshaping the way researchers view Rett and its treatment. By funding his work, IRSF has enabled the exploration of a potential new target for Rett intervention as part of the critical research pillar of our new scientific strategy. I invite you to learn more about how Delaney’s dedication to Rett research and unique approach are helping to create new treatment opportunities in this month’s Inside the Lab.
Dr. Kerry Delaney was simply reviewing a research proposal as a favor to a colleague when Rett syndrome first got his attention.
At the time, Delaney was investigating how neurons, specialized cells in the brain, talk to one another. The grant introduced Delaney to Rett syndrome, and he immediately saw in Rett an opportunity to use his knowledge to make a difference for those living with the disorder.
“It called to me,” Delaney recalls of learning about the disorder, “Those neurons are there. The connections are there. You should be able to…make the connections better.”
Delaney’s interest in working on Rett grew even further when the proposal’s author introduced him to Dr. Patrick MacLeod, a physician-scientist and tireless advocate for Rett research who was the head of Medical Genetics at a local hospital and adjunct faculty at the University of Victoria where Delaney works. Inspired by MacLeod, Delaney launched a Rett research project of his own.
He has dedicated part of his lab to the study of Rett syndrome ever since. Over the years, Dr. MacLeod’s passion for Rett research has continually encouraged Delaney to find new ways to apply his expertise to try to crack some of Rett’s mysteries.
Minding MeCP2 Levels to Answer Questions about Rett
How Rett syndrome affects communication among neurons remains one these mysteries.
During development in the normal brain, neurons connect with one another to form distinct circuits to deliver instructions throughout the body. When a message needs to be sent, each neuron relays the message to the next one in line until it gets where it needs to go, much like people playing a game of telephone. There is also feedback involved in this process that affects how messages are sent and received in the future.
“When you’re processing sensory information or thinking thoughts, there’s this interplay,” Delaney explains, “The way in which the upper brain actually processes the information is not just following [the instructions it receives]. It then sends information…and changes the way [the brain] takes information in.”
This process supports learning and memory in normal individuals. However, it is impaired in girls with Rett because of the different MeCP2 levels among individual neurons. Some neurons have normal MeCP2 levels. Meanwhile, others don’t have any MeCP2 at all due to the MeCP2 mutation that causes Rett syndrome. This difference puts the neurons in girls with Rett on unequal footing in terms of their functioning. Some of the neurons are talking loudly while others are not being heard. As a result, the message that reaches the end of the line is far different than the one that was initiated (as is often the case in a game of telephone).
Researchers don’t yet fully understand exactly how the functioning of neurons is affected by MeCP2 levels because few studies record the MeCP2 levels of individual cells. Delaney’s work does, and it is one of the distinguishing features of his Rett studies. By tracking MeCP2 levels, Delaney’s research can find out if and how MeCP2 levels affect a neuron’s ability to make connections to form circuits and what molecules determine how these connections are made.
Enabling a New Path for Rett Syndrome Treatment
In answering these questions, Delaney may shape the way scientists approach Rett syndrome treatment in the future. For now, most drug development efforts for neurological disorders like Rett syndrome focus on making neurons generally more or less active. Such treatments may not correct the underlying disparity in functioning among the neurons in girls with Rett, which could in turn effect how well they improve outcomes.
“The brain is put together largely through a process of competition. In an environment that is largely [normal] neurons, the mutant neurons actually can’t compete,” Delaney says, citing research his lab published in Frontiers in Cellular Neuroscience in 2015, “[This] highlights the importance of making neurons competitive…We need to target those [mutant] neurons directly and find out what it is we can do to help them.”
Delaney’s IRSF-funded research is designed to enable the creation of such treatments. Because each individual with Rett has a different composition of MeCP2-containing vs. MeCP2-lacking neurons, treatments that specifically target MeCP2-lacking neurons may be essential for some individuals.
According to Delaney, his research wouldn’t be possible without IRSF. He deeply appreciates the funding he’s received and wants donors to know that their investment supports researchers like him who are deeply passionate about solving problems through their studies.
“What [IRSF-funded researchers] are doing is moving the bar forward,” Delaney states, “You don’t know where the ‘aha’ is going to come from. But if you don’t search, you’re never going to find the answer.”
Indeed, the searches IRSF has supported through its investments in research have helped create the treatments that are approaching or are already in clinical trials today. But there are still possibilities- like those that Delaney is investigating- to explore. We will continue to enable this critical research to uncover new treatment approaches because we want to make sure we are creating treatments and cures for every person in our community.