This article was sourced from news stories highlighted by The Cure Parkinson’s Trust.

As the urgent need for disease-modifying therapies for the Parkinson’s community continues, what’s currently leading the way in the research landscape?

Earlier Diagnosis and Treatment of Dementia in Parkinson’s

A research team at the UCL Queen Square Institute of Neurology – led by Dr Rimona Weil – have recently published research that suggests that the monitoring of levels of iron in the brain might eventually help predict which people with Parkinson’s will go on to develop dementia.

A significant number of people with Parkinson’s will eventually develop cognitive impairments or dementia, but the severity and the onset of this affliction are currently unpredictable and vary greatly between people. The identification of biomarkers that can help to detect who will be affected would considerably help with earlier diagnosis and treatment.

Tiny amounts of iron have been found to accumulate in people’s brains as a normal part of the ageing process. In Parkinson’s, however, these levels are higher than normal. And high levels of iron in the body can become toxic, killing cells and leading to proteins being irreversibly altered.    

Many of the proteins associated with neurodegenerative conditions like Parkinson’s are known to interact with iron. Consequently, monitoring iron levels over time could be a useful tool for predicting cognitive issues or dementia in people with Parkinson’s.

In their study, the researchers recruited 100 people with Parkinson’s (and 37 unaffected individuals to act as control subjects), supported by The Cure Parkinson’s Trust. They were administered both cognitive and clinical assessments, as well as a brain imaging technique called quantitative susceptibility mapping (or QSM). QSM determines iron levels in different regions of the brain and then maps them onto MRI images of the brain.

The researchers found that people with Parkinson’s had increased levels of iron in their brains compared with the control group. They also reported that iron accumulation in two regions of the brain involved in memory (the hippocampus and the thalamus) was associated with poor memory and thinking scores in people with Parkinson’s who had not at the time been diagnosed with dementia.

They concluded their study by suggesting that their findings have important implications for brain imaging biomarkers for Parkinson’s and associated conditions, and this could have important applications in both the clinic and in therapeutic trials.

UDCA and Laboratory Cell-Based Parkinson’s

There is a great deal of variability between individuals with Parkinson’s in terms of features, like the symptoms and speed of disease progression. Given these differences, many researchers believe that we may not be dealing with a single condition, but rather a ‘syndrome’ – that is, a collection of different diseases that appear very similar.

This idea has led to a lot of research focused on attempting to define possible ‘subtypes’ of Parkinson’s, where the disease is categorised into groups according to dominant symptoms. This approach will hopefully lead to more targeted and relevant treatments for people with Parkinson’s in the future.

Researchers at Sheffield and Oxford Universities have published research exploring this idea. They took skin cells from 100 people with Parkinson’s and skin cells from 50 age-matched control people without Parkinson’s, and they analysed the health of all the cells according to two functions: energy production within the cells, and how well the cells coped with waste products.

While there was little difference between the Parkinson’s cell samples and the control cell samples in both sets of experiments, there were a lot of differences between the Parkinson’s cells samples themselves – with much greater variability than the control samples – which allowed for distinct subgroups to be identified.

The researchers also treated some of the cells with a drug called ursodeoxycholic acid (or UDCA). This is a medication that is already used for treating gallstones, which has previously demonstrated interesting results in models of Parkinson’s. The researchers reported that UDCA treatment restored the Parkinson’s cells to normal levels of energy production.

Who is Best Suited to Benefit from Genetic-Targeted Therapies?

The Cure Parkinson’s Trust approved funding for a project with Associate Professor, Antony Cooper, Garvan Institute, Sydney, to determine if there is a group of people with idiopathic Parkinson’s (where the cause is unknown) who have a deficiency of their GBA enzyme GCase (glucocerebrosidase) because of DNA changes outside of the GBA gene. It’s predicted that these idiopathic Parkinson’s individuals could benefit from the new therapies that are being developed for the genetic form of the condition – GBA Parkinson’s.

In people with a GBA deficiency – particularly those with GBA gene mutation Parkinson’s – there is a decrease in activity of the GCase enzyme which helps cells dispose of unwanted and potentially toxic surplus material. Dr Cooper is predicting that his research will identify people with Parkinson’s who also have poor GCase enzyme activity but who don’t have a mutation in the GBA gene.

Dr Cooper’s research will use large clinical and genomic datasets, held at the National Institutes of Health in America, of people with both genetic and idiopathic Parkinson’s and healthy individuals, to test whether other changes in their DNA might cause an individual to make less GBA. These small variations in their DNA might impact how Parkinson’s presents in different people. By comparing data from GBA and idiopathic Parkinson’s in this way, we will have a clearer understanding of this stratified group and be able to determine if there is a larger cohort of people with lowered G-Case enzyme activity who might benefit from new treatments targeted to this aspect of Parkinson’s.

This project will also provide a clearer indication of the potential to predict clinical outcomes and help with more direct patient selection criteria for future clinical trials investigating GBA therapeutics in Parkinson’s.

A 15-Year Milestone

2020 is a milestone year for The Cure Parkinson’s Trust – marking their 15th year of investing in pioneering Parkinson’s research, and a chance to reflect on the advances they have achieved within the Parkinson’s arena.

The team are utilising this anniversary as an opportunity to reflect on what they have achieved so far, and look ahead towards a future with renewed confidence and belief in their mission – to slow, stop, or even reverse Parkinson’s.

The Cure Parkinson’s Trust have led the way in bringing real focus to global research and their efforts to engage and refine a more collaborative approach with research teams across the world have helped maintain progress and momentum.

This dynamic approach means that they must maintain their fundraising momentum. 2020 has brought a new drive towards finding a cure. The Cure Parkinson’s Trust have come a long way in 15 years – but another 15 years is too long to wait!

 For more information, visit www.cureparkinsons.org.uk.