May 4, 2015
Staff Reporter

The work of neurobiologist Dr Melanie Cheung (Ngāti Rangitihi) from the University’s Centre for Brain Research is right at the forefront of an international thrust towards enhancing the power of the human brain in sickness and in health. Melanie is leading a team of scientists and clinicians who are seeking to prevent the advance of symptoms in people with the gene for Huntington’s disease: a tragically disabling neurodegenerative disease that is inherited, incurable and inevitably fatal.

And they are doing this in a totally new way: not through a process of drug discovery (though Melanie has done her share of this in the past) but through an intensive programme of carefully-crafted brain plasticity-based cognitive exercises specifically chosen to address the symptoms of Huntington’s disease.

Says Melanie “There’s an adage that says: ‘Neurons that fire together wire together’. If you can get a group of neurons [the nerve cells in the brain that process and transmit information through electrical and chemical messages] to consistently fire together, then you can change a pathway. This process, called brain plasticity, is essentially what our research is about.

“So what we’re trying to do is harness the brain’s natural processes to change the way it functions and stimulate its own pharmaceutical stores in a way that helps it fix itself.

“The types of improvements can be very specific because you can design particular inputs to engage the parts of the brain that need to be strengthened.” All scientists depend on those who have gone before, and this research, funded by the Health Research Council and Fulbright New Zealand, builds on the ground-breaking work of Distinguished Professor Richard Faull (Ngāti Rāhiri, Te Ātiawa), Director of the Centre for Brain Research (and a member of the team), who overturned traditional scientific thinking in the early 2000s through his discovery that the mature brain was capable of growing new cells and repairing itself.

Melanie’s other mentor, supporter and collaborator is neuroplasticity pioneer Michael Merzenich, Professor Emeritus at the University of California, San Francisco, co-founder of Posit Science and author of Soft-Wired: How the New Science of Brain Plasticity Can Change Your Life. His work has resulted in the development of brain plasticity-based cognitive exercises designed to stimulate and strengthen pathways in the brain in order to combat the symptoms of at least 30 different types of neurodegenerative diseases and disorders from autism to Alzheimer’s disease and from schizophrenia to stroke.

With Michael Merzenich, while on a Fulbright Scholarship to the United States, Melanie selected 33 sets of exercises (from among around 200 sets available) that were likely to be effective in addressing the early symptoms of Huntington’s disease: the exercises train attention, working memory, processing speed, sequencing, temporal processing, emotional recognition and mental flexibility.

Using these selected sets of exercises, Melanie and her team have developed a treatment requiring 30 minutes of computer-based “brain training” five times a week over 40 weeks. The exercises are designed to train the participants specifically in those capacities that are impaired in Huntington’s disease.

Forty of these people are doing the selected brain plasticity-based exercises and a control group of 40 are doing a more general cognitive training. Half of the participants are asymptomatic carriers of the Huntington’s disease gene while the other half are members of the same families but are not carrying the gene.

The researchers are not sure if brain plasticitybased training will be able to cure the disease completely. However, Melanie says that they hope to cause a delay in the symptoms and enhance the brain power of all groups in the study. Michael Merzenich’s motto is: “Go faster,” she says.

“As a research team we feel like we’re sprinting. If we can slow the disease progression by five years, in the 40 people with Huntington’s disease that we are training, that will save the Government something like $15 million. And if we can delay the symptoms by five years for those 40 people, that takes away 200 years of human suffering. Take our work out into the world and we might be able to reduce the suffering by hundreds of thousands of years.

“So – we have to go faster.”

The work cuts across the lines between disciplines, as Melanie explains. The participants undergo MRI (magnetic resonance imaging) scans to allow examination of the structure and function of their brains; neuropsychological assessments to measure attention, memory, sequencing, emotional recognition, mental speed and flexibility and verbal fluency; neuropsychiatric assessments to measure the progression of such mental states as anxiety, depression, apathy, irritability (all common among those with Huntington’s disease); and measurement of olfaction (since Huntington’s disease, like all neurological diseases, affects the patients’ ability to recognise smells).

“We are also measuring serum BDNF, a marker for neuroplasticity in people’s blood; [using] the Unified Huntington’s Disease Rating Scale, which assesses the clinical features and course of HD,” she adds.

“What we’re hoping to see is that the dysfunctional pathways become corrected. Even after three weeks of training [already completed at the time of the interview] there are some signs of a lift in mood and improved memory among participants.”

Richard Faull describes this work as “remarkable”: not only because it is the first research in the world to focus on the effects of cognitive exercises on the progression of Huntington’s disease but also because of a second dimension that is an intrinsic part of the research. This is its focus on developing protocols appropriate to Māori researchers and communities.

The base for this dimension of the research was laid more than eight years ago when Melanie (who is of Māori, Asian and Pākehā ancestry) was working towards her PhD, supervised by Richard Faull and Professor Mike Dragunow. At the time her research required that she handle human brain tissue, which would not normally have been acceptable within Māori cultural values and traditions. With advice from Michael Walker (Te Whakatōhea), a Professor of Biological Sciences and a valued mentor, she approached the kaumātua from her own iwi (Ngāti Rangitihi) to ask them to give their blessing for her research.

Richard Faull, Mike Dragunow and Michael Walker came with her to the hui at which the matter was discussed. Also accompanying them were a mother and daughter from a family with the gene for Huntington’s disease. “The human experience was what touched their hearts,” says Melanie. After discussion and consideration, they gave their permission.

When Melanie asked the elders of the iwi for details about the protocol she should use, they said: “You will have to discover it. You are going beyond the boundaries of our knowledge of tikanga”.

Melanie and her team are still on that voyage of discovery: working out the protocols that are appropriate for new research – in a way that is respectful to the culture and the participants, is in accord with Kaupapa Māori, and has the blessing of the communities.

For the current study, most of the research team and all of the project’s participants are Māori, drawn from 14 different communities.

The work incorporates tikanga (Māori values and customary practices) and is very much a combined effort, with a whole clinical team working with the researchers in the communities so that those undergoing the research programme receive the best possible care as they participate in the research.

Over 80 weeks they have four appointments with neuropsychologists and a neuropsychiatrist, seven with the HD specialist nurse, and a yearly whānau hui with the research team. A meeting is also being planned to bring together all the communities.

The team includes specialist research nurse, Jo Dysart, who has had more than 20 years’ experience working with patients with Huntington’s disease, and “knows more about their needs than almost anyone else” says Melanie; Richard Faull, who “plays an important role as a world leader in brain research, but also offers kindness as well as expertise, and has a wonderful way with communities”; Dr Hemi Whaanga (Ngāti Kahungunu, Ngāti Tahu, Ngāti Mamoe, Waitaha), a linguist who looks after translations and ensures clarity of communications; Dr Waiora Port (Te Rarawa, Te Aupōuri) “a wonderful kuia in her 80s who not only guides us with tikanga, but studied Māori experiences of DNA testing for familial cancers for her PhD, so she knows her stuff”; “our brilliant research assistant Emma Lambert” (Ngāti Mutunga, Ngāti Tama), “the top Huntington’s disease neuropsychologist in New Zealand,” Associate Professor Lynette Tippett; Dr Greg Finucane, “our Pākehā HD specialist neuropsychiatrist, “who speaks better Māori than me”; Mike Merzenich, “who is one of the worlds leading experts in neuroplasticity”; and neuropsychologist, Dr Margaret Dudley (Te Rarawa, Te Aupōuri), “who has developed Māori-specific protocols for neuropsychological testing”.

One simple example is that when participants come to the hospital the 0researchers welcome them, karakia, show them around, eat with them, so that they feel at home in what is, to many of them, a “foreign” place.

Says Melanie: “I tell the participants before we karakia that in Māori culture we are taught that karakia is as much about soothing the soul as it is about talking to God. The heartfelt karakia that some of them pray often move us to tears.”

The researchers believe there could be exciting results coming out of the study within six months, leading to a new era of treatment for patients with Huntington’s disease.

They also believe the work is likely to show that the selected brain plasticity-based exercises can significantly enhance brain power in all participants, including those who are healthy (bringing thoughts of a future where every gym would include a computer-room, and a half-hour’s mind-limbering every day would be seen as just as important as a physical fitness regime.)

On several journeys to the United States, including her recent Fulbright Scholarship, Melanie has had the opportunity to develop relationships with other indigenous peoples and to see how the research protocols translate into other cultures. The protocols, she concludes, are about being human. They are about connecting in holistic ways. “We’re discovering that what is good for Māori is likely to be good for others as well.”