An integrated biochemical, genetic and transcriptomic approach to defining target therapeutic pathways in Parkinson's disease

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Parkinson's disease (PD) is a common brain disorder affecting 127,000 people in the UK. It causes slowness of movement and other symptoms such as constipation and memory loss. Unlike cancer medicine, there have been few advances in curative treatment for PD. In cancer medicine patients' treatment is directed not only by where the cancer has developed (e.g. breast, bowel or prostate) but also by the particular proteins that the cancer cells have, so that two people with breast cancer may be treated with two very different treatments. This idea of 'personalised medicine' has proven very successful. Currently all people with PD are given the same type of treatment to help with the symptoms of the condition but no treatments exists to stop or cure PD. Many treatments have shown promising results when tested in mice but when trialled in humans they failed to show any benefit.A key reason for these disappointing results may be that, unlike in cancer medicine, all people with PD are treated the same. PD varies quite considerably within those with condition, for example some have symptoms that worsen over a short period and some have very little change in their symptoms over many years. The reason for this variation is still largely unknown, but one possibility is that although the same part of the brain is affected in all people with PD, how that particular area becomes affected may differ from person to person. Damage to mitochondria (the "power stations" of nerve cells) has long been implicated as an important feature of PD. However, there is now growing consensus that mitochondrial impairment may be greater in some people with PD than others. Therefore if a medicine targets improving the function of mitochondria then it should be trialled on those people where mitochondrial impairment is more important. Unfortunately there is no current way of detecting by symptoms, brain scans or blood tests if a person with PD has significant mitochondrial impairment. As such previous trials of medications targeted at mitochondria have been carried out in an unselected group of people with PD, many of which would not have significant mitochondrial impairment, therefore reducing the chance that the medication would show any benefit.For future trials of medicines in Parkinson's I believe it is important we identify those who would most likely benefit from the medication and target those people to the appropriate trial. Using a novel approach I wish to try and identify a reliable test that detects which people with PD have mitochondrial impairment from a blood sample. Such a blood test would revolutionise drug trials for mitochondrial therapy as not only would it allow the 'right' medication to be directed to the 'right' person (as it is in cancer medicine) but may also act as test to judge if the medication is effective.