What is Parkinson’s disease?
Parkinson’s disease is a degenerative disease of the brain which occurs mainly in older people. It is characterized by an involuntary tremor of the limbs, a slowness of movement (akinesia) and muscular rigidity. Research has shown that the disease is primarily a result of the degeneration of specific pigmented cells which lie in a region deep in the brain called the substantia nigra. Unfortunately, we do not know what causes Parkinson’s disease and why the cells in the substantia nigra degenerate. More research is required to give us a better understanding of exactly what causes the disease.
How has research helped in the treatment of Parkinson’s disease?
Research has been of enormous benefit in the treatment of patients with Parkinson’s disease. The first major breakthrough was the demonstration that the brain cells in the substantia nigra which die in Parkinson’s disease make a special chemical called dopamine. The subsequent use of drugs to replace the low levels of dopamine in the brains of patients suffering from Parkinson’s disease has, in many cases, resulted in a marked improvement of the symptoms of the disease. The first drug treatments for Parkinson’s disease were discovered in the 1960s and are still used today. We are actively making and trialling new drugs for Parkinson’s disease because the original drugs have severe side-effects and do not slow the progression of the disease.
Surgical treatment of Parkinson’s disease
New surgical treatments for Parkinson’s disease are also undergoing investigation. One is a technique called pallidotomy is currently being used for treatment in certain cases. It involves rebalancing the neurotransmitters that are released from the basal ganglia by surgically shutting down one of the brain regions that causes the imbalance in neurotransmitter release. More recently the use of deep brain stimulation (DBS) has become more common. It is like using a pacemaker for the brain. The stimulator can be implanted into the basal ganglia where it electrically stimulates the defective brain region. Studies performed in the brain bank are critical to understanding how pallidotomy and DBS alters the brain’s function and improves the disease symptoms.
Understanding the earliest change in the brain in Parkinson’s disease
Long before the motor symptoms develop in Parkinson’s disease, there have already been significant changes in the olfactory system (smell centre) in the brain. We have been performing experiments to study the earliest events that begin the neurochemical change and cell death that occur in the olfactory bulb. These studies include detailed reconstructions of the olfactory system, identifying the cell types most severely affected, and detailing the number, size and shape of the active units that control the ability to smell (called glomeruli). These studies are being performed in collaboration with a world leading group in Germany who are experts on olfaction. We believe that only when we understand the origins of the disease will we be able to intervene early to possibly stop the disease onset and slow disease progression.
Growing brain cells from brain tissue
Recent work in our laboratories has 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 the 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 on Parkinson’s disease brain tissue
The genetic basis for Parkinson’s disease causation is a weak one and only in approximately 15% of cases is there an identifiable genetic contribution to the disease. Nevertheless, it is important to study the genetics as there may be combinations of genes that contribute to the disease that are not currently known. We are interested in studying novel candidate genes that may improve or worsen the symptoms of Parkinson’s disease and there are new candidates emerging on a regular basis that are of interest to Parkinson’s disease. In addition, in order to study the effects of specific gene expression on human brain cells in culture, we undertake studies involving knocking genes out or expressing them at high levels in cultured human brain cells. We use the cultured human brain cells to test the effects of individual genes on the cultured stem cells
Tracking and stopping the spread of the pathology from one cell to another
There is considerable evidence that the pathological entity (alpha synuclein) in Parkinson’s disease can be passed from one cell to another beginning in the olfactory bulb and then spreading to the rest of the brain. There is debate over how this spread occurs and we are actively studying this process as well as means to stop this spread. Much of this work involves using cultured brain cells and carefully examining the methods cells use to pass a protein from one cell to another.
Drug discovery for Parkinson’s disease
The most commonly prescribed drug for Parkinson’s disease has remained unchanged since Levodopa was first trialled for Parkinson’s disease in 1961. Whilst the drug is effective at improving the motor symptoms it is ineffective at slowing the progression of the underlying disease. We have teamed up with a group of medicinal chemists who are making potential drugs by using novel chemistry techniques. We are then able to screen them for toxicity and for efficacy in cell cultures including on human Parkinson’s disease cells grown from the brain post-mortem. The classification of the drugs and the targets they work on are diverse and the hope is that one or more of these drugs may one day become useful for slowing the progression of the disease.
For emergencies call 111 or visit your nearest hospital
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