Huntington’s Disease 

Huntington’s disease

From its beginnings as a brain bank for diagnosing Huntington’s disease, our human brain studies have expanded with the successful development of techniques for investigating chemicals, proteins, genes and cells in culture and how these change in brain diseases. The human brain consists of several billion nerve cells which communicate with each other by the release of specific chemicals called neurotransmitters. One of the major advances in our understanding of the brain in recent years has been the demonstration that over 100 different neurotransmitters may be present in the brain. Furthermore, recent research has suggested that in Huntington’s disease, the group of cells which degenerate in the basal ganglia utilize certain specific chemical neurotransmitters.

Brain chemistry studies

The results of the chemical studies on Huntington’s brains, which have been bequeathed to the brain bank from all over New Zealand, have demonstrated very specific chemical changes that are now known to be characteristic of this disease. Many of the changes that occur to the brain’s chemistry occur before the brain cells die. Understanding what these chemical changes are and which are affected first is important to know when designing possible therapies. Our current chemical studies involve understanding how the energy consumption and metabolism differs in different parts of the brain when affected by brain disease, which neurotransmitters are reduced and what toxins are produced as a part of Huntington’s disease. One major finding from these studies is the demonstration that there is a marked loss of the chemical γ-aminobutyric acid (known as GABA) in certain parts of the brain. GABA acts by slowing the activity of nerve cells throughout the brain. Unfortunately, giving the chemical GABA to Huntington’s patients not only results in replacing the depleted store of GABA where it is needed but also causes problems in other parts of the brain. However, perhaps patients could be helped if GABA was selectively replaced only in the affected brain regions in Huntington’s disease. Our studies are on-going to investigate which areas are worst affected by Huntington’s disease.

Growing brain cells from brain tissue

Recent work in our laboratories have revealed that human brain cells can be kept alive in cell culture conditions for up to a year after someone dies and donates their brain to the brain bank. This exciting discovery allows us to trial drugs directly on the cells that are diseased and have been affected by a neurological disease. To carry out this technique the post-mortem delay must be minimal and the areas where cells remain alive in the brain must be removed and processed quickly to get optimal cell growth. These brain cell cultures hold great promise for understanding how diseases of the brain affect individual cells and will allow many new therapies to be trialled.

Genetic studies

It is now known that the gene for Huntington’s disease is located on the short arm of chromosome 4 and contains an “expansion mutation” comprising a number of “CAG” repeats. This is a highly repetitive area of DNA, analogous to a typing error, in the human genome. DNA studies of this region reveal the number of CAG repeats. Affected individuals have 36 or more repeats; less than 30 would confirm that one is unaffected, while an intermediate form of 30-35 repeats is equivocal. In order to fully understand and to document the Huntington’s disease gene in each case, it is important to undertake the genetic studies on the brain and also on other tissues of the body such as blood samples. In order to study the effects of gene expression on human brain cells in culture, we will undertake studies involving knocking genes out or expressing them at high levels. We use the cultured human brain cells to test the effects of individual genes on the cultured stem cells.

Stem cells and Huntington’s disease

One of the most exciting developments in our research on Huntington’s disease is the demonstration that stem cells multiply in the Huntington’s brain and produce new brain cells in an attempt to replace the brain cells that die in the basal ganglia. This is the first ever evidence that the diseased adult human brain makes new brain cells and is attempting to repair itself. However, it is just too little too late. We need to try and enhance this normal repair process by finding out what growth factors and other chemicals would stimulate this process early in the disease. In order to do this, we are now developing techniques to culture these stem cells from the human brain in the laboratory, and then study what chemicals enhance cell division and whether the cells can be genetically manipulated to produce these “enhancing” growth factors to not only produce new cells in Huntington’s but also to prevent the cell death in the brain. If we could unlock these “secrets”, this would provide a novel new treatment strategy not only for Huntington’s disease, but also for the neurodegenerative diseases like Parkinson’s disease, Alzheimer’s disease, epilepsy, etc.

Relationship between symptoms and brain disease

Other studies are underway investigating clinical changes in three areas (thinking processes [for example, concentration, memory, planning], mood and emotions, and movement problems), in individuals in whom the diagnosis of Huntington’s disease is suspected or confirmed. Information from this research will be used in conjunction with results from the anatomical, chemical and genetic studies. The aim is to understand and answer questions about the relation between behavioural changes/ mood changes/movement symptoms and the specific chemical alterations, and loss of particular groups of brain cells in different regions of the brain. For example, are the behavioural and mood changes closely related to early-stage chemical changes in the brain, or do they only emerge with the death of brain cells? Are the different patterns of symptoms (mood/motor/behaviour) experienced by individuals with Huntington’s disease caused by the death of different and distinct types of brain cells in the basal ganglia and cortex? Are different patterns of symptoms related to different time courses of the progression of Huntington’s disease? How do these patterns of symptoms relate to gene characteristics? Answers to these questions will help in the areas of prognosis and treatment of individuals with Huntington’s disease.

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Contact Us - Huntington's Disease 

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For general inquiries:

+64 9 923 6072 – Mrs Marika Eszes, Brain Bank Manager

At time of death:

+64 21 287 8476 – Professor Maurice Curtis, Co-Director

The Neurological Foundation Human Brain Bank
Centre for Brain Research
The University of Auckland
Private Bag 92019