Huntington's disease

Many of Brain Research New Zealand's researchers are dedicated to fighting Huntington's disease. Read their stories to find out why they are dedicating their lives to finding treatments and techniques to ameliorate the disease.  

Studying sheep with HD in order to understand the human form of the disease 

Researchers at Brain Research New Zealand: Professor Richard Faull, Professor Maurice Curtis, Professor Russell Snell, Dr Malvindar Singh-Bains and Samantha Murray, are using sheep as large animal models to study neurodegenerative diseases such as Huntington’s disease.

The idea to use sheep to study this disease arose in 1993 in New Zealand. It seemed like an obvious choice given that sheep outnumber humans in this country, seven to one.

Researchers had already identified disorders shared by humans and sheep, but University of Auckland neuroscientist Richard Faull and geneticist Russell Snell had a more ambitious notion. They decided to develop a line of sheep carrying Huntington's, which is brought on by repeats within the gene IT15, in the hopes of studying the condition's progression and developing a treatment. They accomplished their goal in 2006 after extensive efforts.

Why did the team decide to focus on sheep? Because they’re big brained animals —comparable to macaques, which are the only other large animals currently used to study this disease—with developed, cortical folding like our own.

The sheep are kept in large paddocks with their flock and are monitored remotely via data-logger backpacks. This allows researchers to study these creatures in a natural setting. Sheep are also long-lived, social animals with active and expressive behaviour. They recognise faces and have long memories.

The BRNZ and CBR researchers are able to study the full behavioural and cognitive progression of Huntington's disease with the sheep.

The Faull and Snell labs in collaboration with Professor Jenny Morton's lab at the University of Cambridge monitor the flock of Huntington's sheep located in Australia. One flock has been inoculated with one of the most promising therapies yet devised—a virus that silences IT15's mutations—and the other serves as the control flock.

The researchers are hopeful that the studies will lead to a milestone for Huntington’s disease.  

“The tragedy of this disease is enormous. It's a curse on the family. Maybe we can lift that curse,” says Professor Richard Faull.

Read more:

Scientific American

Nature: Metabolic disruption identified in the Huntington’s disease transgenic sheep model

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Solving the mystery of Huntington's disease  

It's called the globus pallidus - and it could be the key to new treatments or a cure for Huntington's disease.

In a new study, Auckland University researchers focused on the specific part of the brain involved in helping us carry out movements.

Movement issues are one of the most common symptoms of the cruel genetic disease, which is characterised by excessive uncontrolled motions called "chorea" and eventual immobility.

Comparing the tissue of Huntington's-affected brains with that of normal tissue, the team looked at how degeneration in the globus pallidus was related to symptoms before death.

They discovered the damage seen in some portions of the region were associated with cognitive problems and all motor impairments - except for chorea.

"This research tells us that in order to deal with the motor and cognitive issues of Huntington's disease we need to repair both of these areas," study leader Dr Malvindar Singh-Bains says.

Because different symptoms were attributable to damage in different areas, the key to curing the disease would not simply be fixing the damage in a single area, she says.

There remained no cure or treatment for the disease, which affects about one in 10,000 people worldwide.

"We desperately need a way to halt the progression of Huntington's disease and one of the ways we can be sure that dream cure will actually work is to know how the disease affects the brain.

"This research puts us one step closer to new treatments or a cure."

Originally published in the NZ Herald 'Brain Detectives: 10 Amazing Kiwi Insights'.  

Reference 

Globus Pallidus Degeneration and Clinicopathological Features of Huntington Disease. Authors Malvindar K. Singh-Bains PhD, Lynette J. Tippett PhD, Virginia M. Hogg MA, Beth J. Synek MD, Richard H. Roxburgh MBChB, PhD, Henry J. Waldvogel PhD, Richard L. M. Faull MBChB, PhD, DSc

Impact Factor: 9.638

ISI Journal Citation Reports © Ranking: 2015: 6/192 (Clinical Neurology); 13/256 (Neurosciences)

 

Can the brain repair itself?

Can the brain repair itself?

We know that after the adult brain is injured - or even when battling a neurodegenerative disease - it can attempt torepair itself using neural stem cells found in specialised regions.

The potential here is phenomenal, yet most damaged neurons in the brain go unreplaced.

It was this promise that led Brain Research New Zealand research fellow Dr Kathryn Jones to investigate a rodent model of Huntington's disease, and a gene therapy approach that used viral vectors containing a neural-promoting gene.

The researchers found they could increase the number of "newborn" neurons that migrated into the brain area where cells were being lost - and even extend this repair process for longer than had been previously observed.

"This opens the possibility for enhancing brain regeneration after injury or disease," says Jones, who collaborated on the study with Auckland University colleague, Associate Professor Bronwen Connor.

"We managed to enhance the normal neurogenic process that was occurring from stem cells found in the adult brain," Dr Jones explains. 

Along with slowing or treating Huntington's disease, the strategy could potentially be used to enhance brain repair after a traumatic brain injury or stroke.

"However, for complete repair after injury, we still need to elicit a larger neurogenic response," Dr Jones says.

"The focus is now on gaining a better understanding of what is stopping this endogenous response working as well as it could."

Originally published in the NZ Herald 'Brain Detectives: 10 Amazing Kiwi Insights'.  

Reference

The Effect of Pro-Neurogenic Gene Expression on Adult Subventricular Zone Precursor Cell Recruitment and Fate Determination After Excitotoxic Brain Injury.  Jones KS, Connor BJ. J Stem Cells Regen Med. 2016 May 30;12(1):25-35. eCollection 2016.

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The Neurological Foundation Human Brain Bank

The Centre for Brain Research at the University of Auckland founded the Neurological Foundation of New Zealand Human Brain Bank in 1994. This houses one of the most extensive collections of human brain tissue in the southern hemisphere, with tissue from nine different neurological diseases and tissue from over 70 normal brains. Research on this tissue provides vital clues about neurodegenerative diseases such as Alzheimer’s, Huntington’s, Parkinson’s, motor neurone disease, epilepsy and schizophrenia.

Tissue from the Human Brain Bank is used by many researchers in New Zealand and around the world, resulting in work published in international scientific journals and papers presented at overseas conferences. This work is highly regarded by colleagues working in similar fields. The Human Brain Bank has provided opportunities for valuable international collaborative studies with leading research scientists in England, Switzerland, Sweden, USA and Japan.

Distinguished Professor Richard Faull is the founder and director of the Brain Bank: 

“Donating your brain for research is one of the most special and invaluable gifts to science. Our researchers treat the tissue with dignity and respect.  Only by working together can we unlock the secrets of brain disease and help find cures to give people hope for the future. That's what our work is all about and we never forget that. This is extremely sensitive and skilled work. We have developed tikanga Māori practices so Māori researchers feel comfortable researching the human brain,” says Professor Faull.  

Read more

What is Huntington's disease?

 [Pictured] An edited microscopic image of medium spiny neurons (yellow) with nuclear inclusions (orange), which occur as part of the disease
[Pictured] An edited microscopic image of medium spiny neurons (yellow) with nuclear inclusions (orange), which occur as part of the disease

Symptoms include:

• Personality changes, mood swings & depression

• Forgetfulness & impaired judgment

• Unsteady gait & involuntary movements (chorea)

• Slurred speech, difficulty in swallowing & significant weight loss

Genetic inheritance of the disease 

• Every child of a parent with Huntington’s disease has a 50/50 chance of inheriting the expanded gene that causes the disease. If the child has not inherited this expanded gene, he or she will never develop the disease and cannot pass it on to their children.

• Huntington's disease is inherited in an autosomal dominant fashion. The probability of each offspring inheriting an affected gene is 50%. Inheritance is independent of gender.

Genetic testing and family planning

• People at-risk for the disease face a difficult choice about genetic testing for HD, given the current absence of an effective treatment or cure. Many people see no benefit in knowing that they will someday develop the disease. Others want an end to uncertainty so that they can make informed choices about the future. The decision whether to test or not is intensely personal and there is no "right" answer.

Young people with Huntington’s disease 

In approximately 10% of cases, HD affects children or adolescents. The symptoms of Youth HD are somewhat different than adult onset Huntington’s and may include stiff or awkward walking, increased clumsiness or changes in speech. The ability to learn new information may decline and the child may lose skills they previous had. Read more at Huntington's Disease Youth Organisation of New Zealand.

 

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The Neurological Foundation Human Brain Bank

The Centre for Brain Research at the University of Auckland founded the Neurological Foundation of New Zealand Human Brain Bank in 1994. This houses one of the most extensive collections of human brain tissue in the southern hemisphere, with tissue from nine different neurological diseases and tissue from over 70 normal brains. Research on this tissue provides vital clues about neurodegenerative diseases such as Alzheimer’s, Huntington’s, Parkinson’s, motor neurone disease, epilepsy and schizophrenia.

Tissue from the Human Brain Bank is used by many researchers in New Zealand and around the world, resulting in work published in international scientific journals and papers presented at overseas conferences. This work is highly regarded by colleagues working in similar fields. The Human Brain Bank has provided opportunities for valuable international collaborative studies with leading research scientists in England, Switzerland, Sweden, USA and Japan.

Distinguished Professor Richard Faull is the founder and director of the Brain Bank: 

“Donating your brain for research is one of the most special and invaluable gifts to science. Our researchers treat the tissue with dignity and respect.  Only by working together can we unlock the secrets of brain disease and help find cures to give people hope for the future. That's what our work is all about and we never forget that. This is extremely sensitive and skilled work. We have developed tikanga Māori practices so Māori researchers feel comfortable researching the human brain,” says Professor Faull.  

Read more

Our Huntington's disease researchers

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Professor Richard Faull

Professor Richard Faull has directed and developed the University of Auckland's Centre for Brain Research since its inception in 2009. He has built one of the world’s pre-eminent neuroscience research centres.

During his 37 years at the University he has established an international reputation for his research studies on the normal and diseased human brain (Alzheimer’s, Huntington’s, Parkinson’s and epilepsy) and has established a Human Brain Bank with the generous support of families to promote worldwide research on human brain diseases. His research group and international collaborators are developing innovative approaches to treat Huntington’s disease using a transgenic sheep model of the disease.

His contributions to research on the human brain have been recognized by appointments as a Fellow of the Royal Society of New Zealand (1998) and an Officer of the New Zealand Order of Merit (2005). He was awarded: the Liley Medal by the Health Research Council of New Zealand in 2005; New Zealand’s highest scientific award, the Rutherford Medal, in 2007 by the Royal Society of New Zealand for outstanding contributions in science; and, received the Supreme Award in the 2010 World Class New Zealand Awards. He was appointed Distinguished Professor at the University of Auckland in 2012, the 2013 Sir Paul Reeves Lecturer and awarded a 2016 Hood Fellowship.  

 

Read more on Professor Faull's Directorate profile

Russel Snell

Professor Russell Snell

Professor of Genetics at the University of Auckland and Principal Investigator for BRNZ, Professor Russell Snell was part of the pioneering team that first identified the gene for Huntington’s disease. That was more than 20 years ago. These days he divides his time between projects on Huntington’s disease, Alzheimer’s disease, and autism. The Snell lab focuses on gene identification, modeling disease processes, and drug discovery in various genetic disorders, including Huntington’s disease, Alzheimer’s disease and more recently neurodevelopmental disorders.

 

“In 1993, we found the Huntington’s gene. The gene is present in every person in the world, but for 1 in every 10,000 people it will cause the development of Huntington’s disease. Who gets the disease, and who does not, is determined by the code of the gene. If a section of the code is repeated too many times it will cause Huntington’s disease to develop.” Professor Snell explains.

 

Nowadays, the team at BRNZ and the Centre for Brain Research are a few years into the Huntington’s sheep project, for which Professor Snell is a founding member and collaborator. Scientists are preparing to test a potential therapy for Huntington's disease in sheep that have been genetically modified to carry the mutation that causes the disease.

“In five years’ time, I would be surprised if we didn’t have some good first base treatments for Alzheimer’s, Parkinson’s, and Huntington’s” explains Professor Snell.

Read more about Professor Snell

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Professor Tim Anderson  

Professor Tim Anderson is a movement disorder specialist, a BRNZ Principal Investigator, the Clinical Director at New Zealand Brain Research Institute in Christchurch and Professor of Medicine at the University of Otago in Christchurch.

He also has an appointment as a neurologist with the Canterbury District Health Board (CDHB) Department of Neurology, and also undertakes a small amount of private practice.

His particular interest and expertise is in the field of Movement Disorders - a subspecialty concerned with Parkinson’s disease, Huntington’s disease and other neurological conditions that cause tremors (shaking) muscle spasms and muscular jerks.

He undertakes two specialised CDHB clinics every week, diagnosing and treating patients with these conditions. In addition he treats debilitating muscle spasms (torticollis, facial spasms, foot or hand spasms) with botulinum toxin (“botox”) in a dedicated half-day clinic every fortnight.

There are also weekly research clinics related to participation in international research studies and pharmaceutical trials of new medications. One of these ongoing studies is the Enroll-HD study. This is a huge international study that will ultimately include thousands of people with Huntington’s disease (HD) and their families funded by a private organisation CHDI (Cure Huntington’s disease Initiative) with the aim of establishing a massive international Huntington’s database as a springboard and catalyst for further research into this devastating inherited disorder.

Read more about Professor Anderson

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Associate Professor Deborah Young

Associate Professor Deborah Young is a Principal Investigator for both the Centre for Brain Research and Brain Research New Zealand at the University of Auckland. 

The Young Lab specialise in Gene Therapy and Assoc. Prof Young's research interests are broad and range from the study of the molecular basis of learning and memory, to gene therapy of neurological disorders. 

 

The Young lab's research covers the full spectrum from molecular biology through to animal behaviour and human clinical trials. Promising approaches are advanced to human clinical trials.

Many of Assoc. Prof Young's projects involve collaborations and her laboratory is of international standing and forms a key role in a major network of mammalian brain gene interventionists.

The gene therapy group is an international collaborative group of investigators at Auckland and Ohio.

Assoc Prof Young's research into Huntington's disease includes developing genetic models of Huntington's and Alzheimer's diseases and the development of therapeutic strategies for these diseases.

Read more about Associate Professor Young

maurice

Associate Professor Maurice A Curtis

Associate Professor Maurice A Curtis is currently an Associate Professor in Anatomy at the Department of Anatomy with Radiology. He is a Principal Investigator for both the Centre for Brain Research and Brain Research New Zealand at the University of Auckland. Maurice is Head of the ‘Human Neurogenesis and Progenitor Cell Migration Laboratory’ and is also Deputy Director of the Neurological Foundation of New Zealand Human Brain Bank.

Prior to this he was a post-doctoral researcher at Gothenburg University in Sweden where he spent four years studying pathways for progenitor cell migration in the human brain and in understanding the replacement of neurons in the adult human brain. The work he performed there has contributed significantly to our understanding of which areas in the human brain respond most to neurodegenerative diseases by increasing the production of new neurons in a reparative way. Maurice was the first to show that the human brain attempts to repair itself after it is affected by disease and also the first to show that there are pathways that progenitor cells migrate on.

Currently his group is focussed on understanding the control of progenitor cell migration and how this process becomes dysfunctional in neurodegenerative diseases such as Huntington's disease. 

Read more about Associate Professor Curtis 

BRNZ_Henry Waldvogel_1

Associate Professor Henry Waldvogel

Associate Professor Henry Waldvogel’s main area of research is the chemical neuroanatomy of the normal human brain and the changes that occur in the brain in neurodegenerative diseases particularly in Huntington's disease, but also in Parkinson's, Motor Neuron disease and Alzheimer's.

He studies the cell death and neurochemical changes that occur in the human brain in neurodegenerative disease with a major interest in the inhibitory neurotransmitter receptors GABAA GABAB and glycine receptors and their associated proteins as well as neurochemicals specific to all types of brain cells. These neurochemicals are studied at both the regional and cellular level with high resolution light and confocal laser scanning and electron microscopy.  Tissue microarrays are also being developed.

Assoc Prof Waldvogel also researches animal models of Huntington's disease, especially the transgenic sheep models that have been developed in a large international collaborative study with researchers at Harvard, Cambridge and Adelaide Universities. The Waldvogel and Faull labs are studying the neuropathological changes in this sheep model in order to understand the mechanisms of cell death caused by the mutant Huntington’s gene and to trial therapeutic strategies.

Assoc Prof Waldvogel explains his work in relation to the Neurological Foundation Human Brain Bank:

“We now know what each cell type in the brain does. When it’s lost we can now correlate that to the symptoms. Psychologists and clinicians can detail the symptoms that those people had when they died, and we can then look at what has actually changed in the brain. Ultimately we can help treat these diseases by targeting the regions of the brain that are most at risk.”

Read more about Associate Professor Waldvogel

mel cheung

Dr Melanie Cheung

Dr Melanie Cheung (Ngāti Rangitihi, Te Arawa) is committed to exploring both Indigenous and Western scientific paradigms to help people with neurodegenerative diseases. Consequently, her work integrates experimental neurobiology, bioethics, tikanga (ceremony/customary) and Mātauranga Māori (Maori traditional knowledge).

Since 2007 Melanie and her research team have worked closely with a large Taranaki Māori family that have Huntington’s disease, a dominantly inherited neurodegenerative disease that affects movement, personality, and higher cognitive functions. 

Dr Cheung’s previous research projects have included: Āta Photovoice Research Project highlighting the Taranaki families’ wellbeing practices; Te Mata Ira, a bioethics project investigating Māori views on biobanking and genomic research; Validating a transgenic songbird model of Huntington’s disease (with Rockefeller University, New York); The isolation and culturing of 19 novel primary human cell culture models of brain disease; Using Indigenous values and practices in scientific practice, with specific focus on developing culturally respectful laboratory practices for working with human tissue. This research was featured in Science (2007, 318:907) and ABC’s award winning All in the mind radio show (3 May, 2008).

Read more about Dr Cheung

Malvindar Singh-Bains

Dr Malvindar Singh-Bains

Neuroscientist Dr Malvindar Singh-Bains is a research fellow at Brain Research New Zealand, the Centre for Brain Research and the Neurological Foundation of New Zealand's Human Brain Bank. She gained her PhD in 2014 under the supervision of Distinguished Professor Richard Faull and Associate Professor Henry Waldvogel. Her PhD focused on neurodegeneration of the human globus pallidus in Huntington’s disease (HD), but it’s her work for the Huntington’s community for which she has received considerable acclaim. 

She’s passionate about research into neurodegenerative diseases: particularly Alzheimers and Huntington's disease. In addition to research work, she is a public awareness campaigner, educator and two-time finalist for the Young New Zealander of the Year award. 

She is a founder and chairperson of the Huntington’s disease Youth Organisation of New Zealand (HDYO-NZ), a charity dedicated to support and educate young New Zealanders impacted by HD. She promotes brain health awareness among young people and has visited several schools nationally over the past five years as a volunteer to promote the importance of ‘looking after your brain.’ 

“At BRNZ and CBR, we’re encouraged to go into the community and talk about our research. People are intimidated by the idea of scientists in white coats. So we are trying to change that stereotype. If you’re able to explain simple terms the research you’re doing, not only are you educating people, you’re creating awareness of Huntington’s disease. You wouldn’t believe the number of people who I talk to about it, who haven’t heard of Huntington’s before. Yet we have over 800 people in the Auckland region on the Huntington’s gene database. We don’t want people to stare, we want people to understand the symptoms of HD,” Dr Singh-Bains explains.  

Listen to the full interview with Dr Singh-Bains on Radio NZ’s Nine to Noon programme.

Read more about Dr Singh-Bains

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Associate Professor Lynette Tippett

Lynette Tippett is an Associate Professor of Psychology at the University of Auckland since 2012. A major focus of her research programme involves clinical and neuropsychological investigations of individuals with neurological disorders, particularly neurodegenerative diseases (Huntington’s disease, Alzheimer’s, Motor Neuron disease and Parkinson’s disease).

Central to the success of this research are strong multi-disciplinary research teams, linking bench-top neuroscience with clinical science and patients.

In recent years, Assoc. Prof Lynette Tippett has been pivotal to the establishment of New Zealand’s first Dementia Prevention Research Clinic located in Auckland. She is the Director of what will become a nation-wide network of clinics and is also the co-director of the Auckland clinic along with geriatrician Dr Phil Wood. Following the opening of the first clinic in Auckland, two other clinics are planned for Dunedin and Christchurch.  

Read more about Associate Professor Tippett

Dr Nasim Mehrabi along with Assoc Prof Henry Waldvogel and Professor Richard Faull

Dr Nasim Mehrabi

Dr Nasim Mehrabi is a research assistant working on Huntington’s disease at the Centre for Brain Research and Brain Research New Zealand. Her work with human brains combines two of her favourite research areas, genetics and neuroscience.

“I have the privilege of working with post-mortem human brain. My research focuses on understanding how Huntington’s disease affects different parts of the brain. Particularly, I am interested in understanding the variable symptoms that are associated with HD. we need to understand the early changes in the brain that are associated with HD before we could come up with new therapeutic strategies. 

“Huntington’s disease is so complex, yet so simple. It is caused by a mutation in a single gene. The simple part is the mutation in a single gene. The complex part is all the downstream effects caused by that “mutation”. We, Huntington’s disease researchers, think that HD is one of the most curable neurodegenerative disorders, because we have a very strong lead, the gene,” Dr Mehrabi explains.

Dr Mehrabi’s biggest motivation is Huntington’s disease patients and their families. 

 

“I have had the privilege of meeting a few HD families throughout the past couple of years, and I can say that nothing excites me more than seeing hope in their eyes. After talking to HD families, I find myself more passionate, more focused and more motivated than ever before. They help me to see the bigger picture, to imagine better! I think we all hope for a cure! We are all working hard to understand the disease and how it affects the brain, so that we can come up with better treatments. I know it is a big ask, but this is what we need to work towards to. I guess we need to dream big,” explains Dr Mehrabi. 

Read more about Dr Mehrabi

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Samantha Murray

Samantha Murray is a PhD Candidate at Brain Research New Zealand and Centre for Brain Research. She is conducting research into the changes in the brain during the early stages of Huntington’s disease.

“I am working on finding out what’s changing in the brain in the very early stages of HD. If we know what these early pathological changes are, we can develop drug targets to stop these changes occurring and hopefully slow down or stop the progression of the disease. I am also interested in how gene therapy can stop the progression of HD, and how early biomarkers of disease progression can inform us on the most appropriate time to administer such therapies,” Miss Murray explains. 

Samantha is totally committed to spreading awareness about Huntington’s disease and is the Scientific Advisor for Huntington’s disease Youth Organisation of New Zealand.

“My original motivation for wanting to study Huntington’s was having a family friend with the disease when I was younger. So I wanted to learn about the disease and do something to help. Now, having been in the HD research field for a few years, I’ve met patients and family members through my work. Their stories, resilience and hope is what drives me each day to work hard in the lab to push the boundaries of HD research and eventually work towards a treatment for HD,” Samantha explains.

Read more about Samantha Murray