What is Motor Neurone disease?
Motor neurone disease is a degenerative disease of the brain and spinal cord which occurs mainly in older people. It is characterized by progressive weakness and atrophy of the muscles, due to the loss of the motor neurones that control those muscles. The onset of symptoms is most frequently seen in the limbs however about one quarter of patients experience symptoms which first affect speech or swallowing. Unfortunately, we do not know what causes motor neurones to degenerate in motor neurone disease; while 5-10% of patients have a family history of the disease, most patients are affected seemingly “out of the blue”. Much more research is required to understand the causes and processes involved in the disease so that treatments can be developed.
Genetic studies of Motor Neurone disease brain tissue
As of 2014, research has identified around 30 faulty genes that can cause motor neurone disease. Around 15% of patients have one of those faulty genes, including some patients with no family history. The same genes that cause motor neurone disease can also cause a type of personality-changing dementia called frontotemporal dementia. For most motor neurone disease patients, it is likely that a combination of genetic risk factors and environmental agents cause the disease. Identifying more of the genes that cause disease will help us to identify the cell functions which, when disrupted, cause motor neurones to degenerate. We perform this “gene hunting” work in collaboration with colleagues in the United Kingdom, who have previously identified two of the most common faulty genes that cause motor neurone disease.
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 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 the 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 motor neurone disease affects individual cells and will allow many new therapies to be trialled.
Blood-brain-barrier studies in Motor Neurone disease brains and brain cells
Blood vessels in the brain and spinal cord are tightly wrapped with cells that prevent vessel leakage. Evidence suggests that in motor neurone disease the blood vessels are wrapped with fewer of these cells, which might allow vessels to leak blood-borne chemicals into brain tissue. We are testing whether the disruption of this blood-brain-barrierhappens in the same areas of the brain where motor neurones are damaged. Because the cells we grow from patient brain tissue are these same cells that wrap the blood vessels, we can test how the cells differ between motor neurone disease patients and controls.
Protein accumulation in Motor Neurone disease brains and growing brain cells
Proteins perform important roles in all cells but if they become damaged or are no longer needed, they must be broken down and recycled by the cell. In motor neurone disease there are clumps of waste protein in the motor neurones suggesting that the disposal processes are faulty. We examine the build-up of waste proteins in different brain and spinal cord regions and use growing brain cells from patients to test the function of the protein disposal processes. We hope to identify drug molecules which can kick-start the disposal processes back into action.
Drug discovery for Motor Neurone disease
We have teamed up with a group of medicinal chemists at The University of Auckland who are making potential drugs by using novel chemistry techniques. We are then able to screen those drugs for toxicity or, ideally, protection of cells grown from the donated brains of motor neurone disease patients. We can then examine the cell functions targeted by effective drugs both to learn more about disease and to further tailor our drug screening to those important targets.
How will research help in the treatment of Motor Neurone disease?
Currently Riluzole (Rilutek) is the only drug approved to treat motor neurone disease. Riluzole was discovered in the 1980s and was trialled in motor neurone disease patients based on the more limited understanding of the disease at that time. We have since learned a vast amount more about motor neurone disease so the drugs we choose to test are ever more likely to be useful to patients. A large number of pharmaceutical companies and research laboratories including our own are now testing for new drugs for motor neurone disease. It is our hope that a new treatment that surpasses Riluzole is on the horizon.
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