Breakthrough for Parkinson’s disease

Parkinson’s disease is a progressive neurodegenerative condition which affects the central nervous system. The disease is caused by a lack of dopamine-producing cells in the substantia nigra region of the brain. Without sufficient dopamine, movement are slow, giving rise to the common motor symptoms including tremor, bradykinesia (slowness of movement), rigidity and postural instability, and the neuropsychiatric symptoms including, executive dysfunciton, memory loss and depression (1).

Statistics from the Parkinson’s UK website report that 1 in 500 people have Parkinson’s disease, which is equivalent to approximately 127,000 people in the UK. Although the majority of these people are over 50 years old, 1 in 20 are under 40.

The breakthrough

On the 7th February, a paper entitled ‘Parkin controls dopamine utilization in human midbrain dopaminergic neurons derived from induced pluripotent stem cells’ by Jiang et alwas published in Nature Communications. The paper reported the successful creation of human brain cells that are exact replicas of cells in Parkinson’s disease. The study was based on the hypothesis that a type of Parkinson’s disease can be caused by mutations in genes such as parkin.

In the study, Jiang and his team for the first time were are able to generate pluripotent stem cells from normal subjects and PD patients with mutations in parkin. Pluripotent stem cells are able to develop into different types of cells, for example skin, blood, brain and bone, by a process known as differentiation. They are self-renewal and have the potential to be used in treatment to repair and renew mutated or deficient cells to treat diseases. These stem cells were transformed into brain cells that are seen in patients with mutations in parkin. This remarkable step, is the first time that scientists have been able to artificially reproduce these cells, in order to examine the mutations that cause the Parkinson phenotype, meaning that the exact mutations that cause the disease can now be fully investigated,

The study demonstrated that loss of the parkin gene, increased the transcription of monoamine oxidases and oxidative stress, significantly reduced the uptake of dopamine, and increased the spontaneous release of dopamine. The scientists used expression of lentivirus to insert the parkin gene to demonstrate that parkin controls dopamine levels in the brain and enhances its transmission. Therefore, indicating new targets for treatment and diagnosis. If scientists are able to develop a clinical method of inserting normal parkin into mutated cells, they might me able to prevent this type of Parkinson’s disease from occurring.

The future of treatment

The work from this study could be the key to developing future personalised treatments, which target mutations in parkin. They study also opens the door to studying the brains complex circuitry and pathways.

This accomplishment, Feng says, is advancing not only the study of Parkinson’s but other neurological diseases simply by enabling researchers to non-invasively study the disease at its cellular level. “It finally allowed us to obtain the material we needed to study the disease”.

Dr Feng said “This is the first time that human dopamine neurons have ever been generated from Parkinson’s disease patients with parkin mutations. Before this, we didn’t even think about being able to study the disease in human neurons. The brain is so fully integrated – it’s impossible to obtain live human neurons to study”.

Dr Michelle Gardner, Research Development Manager at Parkinson’s UK, concluded that “New stem cell technology which allows nerve cells to be made from adult skin cells is opening doors for research into Parkinson’s”.

This is an exciting and optimistic time for Parkinson’s researchers and patients, as a step is taken toward treatment for this currently incurable disease.