Review 2019: Research Highlights We have had a great deal of research-related news throughout the year, but 5 highlights stand out in 2019. The publication of the Bristol GDNF clinical trial results: The Cure Parkinson’s Trust (CPT) has been instrumental in promoting research of the neurotrophic protein, glial cell-derived neurotrophic factor (GDNF), and in 2012 we co-funded a pioneering clinical trial in Bristol (UK) which explored the potential use of this neurotrophic factor in slowing the progression of Parkinson’s. In February 2019, the results of the Phase II Bristol GDNF clinical trial were published in the prestigious medical journal Brain. The study involved 41 individuals having a pioneering delivery mechanism implanted in their brains and blindly being treated with either GDNF or a placebo for 40 weeks. The results suggested that the treatment was very safe, but there was no difference between the treatment and control groups at 40 weeks (as determined by clinical rating scales*). There were, however, some interesting findings in the data, which were encouraging, and CPT is continuing to explore GDNF further. Find out more about the Bristol trial here. At the same time that the trial results were published, a documentary featuring nine of the GDNF trial participants who were filmed during the study was aired on the BBC. This documentary - “The Parkinson's Drug Trial: A Miracle Cure?” - recently won the prestigious Grierson Award for 'Best Science Documentary.' Find out more here. *The Movement Disorders Society Unified Parkinson's Disease Rating Scale The Australian Parkinson's Mission: In February, the Australian government initiated the Australian Parkinson's Mission (APM) - a commitment to provide A$30 million funding for a 5 year clinical trial programme in which CPT is a partner, along with the Michael J Fox Foundation, Shake it Up Australia and the Garvan Institute of Medical Research, Australia. The project will begin with a large multi-arm clinical trial, which is an approach that allows for the testing of 4 drugs at the same time against a single placebo treatment. 300 people with Parkinson’s participating in the trials will be randomly assigned to one of 5 groups: one will be treated with a placebo drug while the other groups will be administered one of the 4 drugs that have been prioritised by the international Linked Clinical Trials programme (which is co-ordinated by CPT and the Van Andel Institute). Once the first trial has started, additional multi-arm trials will be initiated. The research team at CPT is extremely excited by the APM project as it will not only allow for the clinical testing of 8-12 potentially disease modifying therapies over the 5-year time frame, but there will also be added value in sub-studies surrounding these trials which will enhance our understanding of Parkinson’s and allow for the testing of new methods of assessment. Find out more about the APM. The initiation of the Phase III Bydureon clinical trial: In late 2017, the results of a Phase II clinical trial evaluating the diabetes drug Bydureon (also known as exenatide) in people with Parkinson’s indicated that the treatment was having an effect on the motor skills of participants. Individuals in the Bydureon treatment group saw some stabilisation of their motor features over the course of the 48 week study, while the placebo treated group continued to worsen. This year, a larger Phase III clinical trial of Bydureon in 200 people with Parkinson's was registered. The study will be conducted across 6 sites in the UK and will involve the participants being treated and assessed for 2 years. CPT has been involved with the testing of exenatide in Parkinson's from the very beginning and is co-funding multiple substudies connected to this large Phase III trial (in collaboration with the Van Andel Institute). Find out more about this next trial phase. The start of the UDCA in Parkinson's clinical trial - ('UP study'): 2019 saw the initiation of the UDCA in Parkinson's clinical trial - the 'UP study'. This study involves a clinically available treatment called ursodeoxycholic acid (or UDCA) which is used to treat gallstones. Preclinical research has demonstrated that UDCA has beneficial properties in models of Parkinson's and the drug was prioritised by the international Linked Clinical Trials committee for clinical testing. The UP study will evaluate UDCA in 30 people with Parkinson’s. The primary goal of the study is to determine if the drug is safe and tolerable at the dose being used, but some measures of efficacy will also be collected. The study is now fully recruited and we expect to learn the results in early 2021. Find out more about the UP study. The Publication of a Potentially Useful Biomarker Approach: International Linked Clinical Trials committee member Professor Tom Foltynie, and an international team of researchers, published a seminal report demonstrating how blood-based biomarkers can be used for measuring drug impact and activity in the brain. The researchers extracted brain-derived 'exosomes' from blood samples of people with Parkinson's who participated in the phase II exenatide clinical study. Exosomes are small cell-derived sacks, which contain various proteins. Cells release exosomes as a way of disposing of unwanted material, or to send chemical communications to other cells. Prof. Foltynie and his team identified specific 'markers' which allowed them to identify exosomes which originated in brain cells, as opposed to other cells in the body. By analysing the contents of these brain-derived exosomes, the team were able to assess the consequences of exenatide treatment, and - in this way – demonstrate drug interactions. By analysing brain-derived 'exosomes' from the phase II exenatide clinical study, the researchers found that the treatment had augmented insulin signalling inside the exosome - suggesting that the drug was having an effect inside the brain. If replicated, the implications of this research are potentially huge as they could provide an objective measure of 'target engagement' of drugs in the brain from simple blood samples. And, equally important, this simple technique could be used across all clinical trials focused on neurological conditions. Find out more about this breakthrough research. What Next? The research team at CPT now look forward with considerable anticipation to the publication of results from two recently completed clinical studies:Ambroxol – a respiratory drugEPI-589 – a new drug that supports energy production in cells We also have 3 clinical trials that will be finishing in the coming months and we look forward to the publication of their results:Simvastatin – a cholesterol lowering drug Deferiprone – an iron reducing agentLiraglutide – a diabetes drug similar to exenatide There will also be a number of new clinical trials starting for potential disease-modification in Parkinson's, including the first large multi-arm study within the APM project, as mentioned. In addition, we will see the results of numerous CPT funded pre-clinical studies which will be instrumental in providing the case for support for future clinical trials in Parkinson’s. We'd like to take this opportunity to thank everyone for your support - there is a lot to look forward to in the coming year. We will keep you informed!