There has been a lot of research done on trying to identify the genetic causes of Parkinson’s. One of the most common mutations that has been found associated with hereditary Parkinson’s is a mutation in a gene called Leucine-Rich-Repeat-Kinase 2 (LRRK2, more commonly referred to as Lark-2).
Parky people with a Lark-2 mutation show an increase in the activity of the work done by Lark-2 but not all people who carry a Lark-2 mutation will develop Parkinson’s, so we are far from understanding the mechanisms around this.
Everyone has a Lark-2 gene, which is expressed (i.e. doing its job) in all brain regions but is at very low activity levels in all other areas of the body. Lark-2 does its job by adding phosphate molecules to itself as well as other molecules in the brain, which makes these other molecules active; active molecules made by Lark-2 ensure the successful transmittal of nerve signals through the axons, they maintain neurites (any projections from a neuron e.g. axons or dendrites) and are also key in the pathway of axon guidance (where they grow and how long they are) and synapse formation (essential for transmission of nerve signals).
Any cell in the body excretes waste products by sealing all the stuff it doesn’t want into a ‘vesicle’ which is expelled from the cell (like putting out the bin bag!) and these find their way out of the body into the urine. One of the ‘waste products’ that can be detected is Lark-2 itself. It turns-out that we can measure how active Lark-2 in urine by measuring the number of phosphates it contains. I have already mentioned that Parky people with a Lark-2 mutation show overactivity in these molecules (there are too many phosphate molecules added – a bit like over-fertilising your allotment) but scientists in the USA have also discovered that this overactivity can be detected in 20% of Parky people who have a normal Lark-2 gene, and this test can be performed on a urine sample (the original scientific article can be found here).
This is an exciting discovery because it not only gives us a method of detecting Parkinson’s early but in people who have this mechanism behind their Parkinson’s, this could also be a way of detecting if, and subsequently, how well a drug therapy is working.
The work is still in preliminary stages and more studies are in the pipeline to work-out if this is a potential breakthrough.
Meanwhile, on the other side of the planet, Australian scientists have been working on blood samples to see if there is diagnostic potential – and in the process of doing so, they have made an astonishing discovery.
We have heard about the importance of mitochondria and the potential role that they play in Parkinson’s at our researcher meetings, so these cellular ‘power-houses’ are no strangers to us. The current understanding is that there is a toxic build-up of by-products from energy metabolism, caused by a defect in the mitochondria. However, the Australian team, led by Professor Paul Fisher, found that there was no damage to mitochondria in Parky people. Rather than the mitochondria being dysfunctional, working more slowly and therefore toxic byproducts building up, Fisher’s team discovered that the mitochondria were working four times as hard, which was also leading to a build-up of poisonous chemicals.
There is, as always, plenty of work to be done to see whether this hyperactivity of mitochondria is present exclusively in Parkinson’s or whether it occurs in other types of neurological disease. Funding has been provided from the Michael J Fox Foundation and Shake It Up Australia Foundation to do further research into the potential of this blood test.
Both of these discoveries have the same aim; to diagnose people with Parkinson’s at the earliest possible stage, hopefully before they have symptoms, so that interventions and potential disease modifying agents can be used to slow or stop the progression. However, it would also be good to have a tool for definitive diagnosis, rather than the diagnosis being based on a series of non-specific tests and a process of elimination that still carries the risk of a person being treated for a condition that they do not have.
I will continue to watch this space with interest!