Anette Schrag, FRCP, PhD, University College London, London, UK, highlights an exciting time in Parkinson’s disease (PD) research as it transitions from the use of symptomatic treatments towards the potential of disease-modifying neuroprotective therapies that can target specific aspects of the PD disease process and patient subgroups. Prof. Schrag also outlines some of the current challenges associated with conducting PD clinical trials including the lack of reliable biomarkers to study disease-modifying effects and limitations associated with current clinical outcome measures. This interview took place during the AD/PD™ 2021 conference.
Transcript (edited for clarity)
The session at the AD/PD sponsored by Roche was about really the transition period that we’re now in, from purely symptomatic treatment in Parkinson’s disease to a focus on also potential neuroprotective treatments for Parkinson’s disease. We have had symptomatic treatments for Parkinson’s disease for many years or decades and this clearly has been of huge benefit to our patients but they are not perfect, particularly in the more advanced stages and therefore, there has been a hunt for treatments that could potentially delay progression of the disease...
The session at the AD/PD sponsored by Roche was about really the transition period that we’re now in, from purely symptomatic treatment in Parkinson’s disease to a focus on also potential neuroprotective treatments for Parkinson’s disease. We have had symptomatic treatments for Parkinson’s disease for many years or decades and this clearly has been of huge benefit to our patients but they are not perfect, particularly in the more advanced stages and therefore, there has been a hunt for treatments that could potentially delay progression of the disease. Now, there have been a number of trials over the years and none of them have really been able to show that the treatment is able to delay progression of the disease itself.
And similarly to other diseases such as Alzheimer’s, Huntington’s disease, there are a number of reasons for that and in Parkinson’s disease, the great symptomatic effect of the treatments we have at the moment is an added complication and that is because it is such an important confounder that any potential neuroprotective effect of medication is sometimes quite difficult to discern, particularly as some of these may have not only immediate but also longer-term effects. And that has also led to approaches to look at biomarkers, to study potential disease-modifying effects, similarly to AD and HD but unfortunately, at the present time we don’t have a reliable and robust and exact biomarker.
There are a number of candidates and most prominently we have dopamine transporter imaging, but there are some difficulties with that, not least that there is not an optima correlation with the clinical outcome measures. There are a number of biomarkers being explored and we’re particularly interested in the ones that are easy to apply proof of biomarkers, whether it’s in the blood or in skin and there have been a number of interesting presentations at this AD/PD meeting but at the moment, we really rely on clinical outcome measures.
We have one key outcome measure, the MDS-UPDRS. These clinical outcome measures have their limitations. We therefore really quite urgently need more precise and perhaps also outcome measures that can supplement the MDS-UPDRS. There’s not just an issue with the Optima outcome measures, but of course Parkinson’s Disease is extremely heterogeneous. It presents not just with motor symptoms and even those change over time and are quite varied, but also the Parkinson’s Disease is characterized by a range of different non-motor symptoms and this makes it quite difficult to have one outcome measure that fits all.
Patients are heterogeneous and the overall population of patients with Parkinson’s Disease has been subtype and various subtype groupings have been proposed. And most importantly, perhaps we now know that there are gene carriers who are at risk of Parkinson’s disease and with increasing understanding of the underlying pathophysiology, particularly in these subgroups, there might be a window to particularly study disease progression in these subgroups and not just genotype-characterized subtypes, but also patients with particular clinical subtypes such as REM sleep behavior disorder, who we know are much more likely to develop a Parkinson’s disease or another nuclear neuropathy then controls and also may behave differently once Parkinson’s disease has developed.
Given that we have a number of different potential treatments now, which address different aspects of the Parkinson’s disease pathophysiology, it may be possible in the future to target different aspects or conduct trials, targeting specific aspects of the disease process and design trials that are specific to these specific subgroups. So we’re really at a very exciting time in research in Parkinson’s disease where we are at the cusp of shifting from purely symptomatic treatments to potentially neuroprotective treatments and there are a range of different potential treatments available targeting different aspects in the pathophysiology of Parkinson’s disease and this will help us in the future, not only to improve the symptoms, but also change the trajectory of disease progression and thereby reduce disability and symptoms in the future.
Prof. Schrag has received consultancy fees from Roche, Biogen and Abbvie and grant support from GE Healthcare in the last 12 months.