Cutting Edge Science for Parkinson’s Clinicians was an educational meeting sponsored by Bial Pharma UK Ltd, and delivered in association with the Parkinson’s Academy. This one-day meeting, chaired by Dr Peter Fletcher set out to review advances in the clinical understanding of Parkinson’s, and discuss how to build on these insights in routine clinical practice. As Dr Fletcher noted “Science provides the building blocks, the art is applying the evidence to the patients sitting in front of us”.
Professor Huw Morris began his presentation on genetic testing with its conclusion – that there is, indeed, an increasingly urgent need to rethink how genetic testing is used in Parkinson’s. In a world that is rapidly moving into a new era of readily available genetic testing, clinicians need to be ready to understand the complexities of ethics and consent issues that such testing brings. Patients increasingly want to know if their Parkinson’s has a family basis, and we can expect increasing numbers of genetic-based cases as the population ages. Services must also be ready with the necessary framework for genetic and family counselling, as a genetic diagnosis has profound implications for the whole family.
Moving onto imaging, Dr Donald Grosset called for clinicians to also rethink how they use imaging within their clinical practice. Like genetics, the imaging field has taken big steps forward in recent decades, and Parkinson’s services must consider how best to make use of these important tools. For example, in patients with a prominent tremor, DaTscan imaging can help differentiate between Parkinson’s and essential tremor. However, an abnormal scan will not clearly differentiate between Parkinson’s and Parkinson’s plus syndromes. It is also vital that clinicians understand there are always exceptions to every rule. For example, the current threshold for detection on DaTscan means that patients with very early Parkinson’s may initially show a normal scan, that changes with disease progression.
Dr Daniel van Wamelen took the audience on a whirlwind tour of therapies for Parkinson’s. Starting with the available therapies, he noted that the new NICE guidelines continue to recommend a choice of MAO-B inhibitors COMT-inhibitors, or dopamine agonists as adjunct therapy to levodopa. In terms of new COMT inhibitors, Dr van Wamelen described recent studies that show that the COMT-inhibitor opicapone given once daily reduces OFF time by about an hour versus placebo, increases ON time without troublesome dyskinesia, and is non-inferior to entacapone given with each levodopa dose. Moving to more advanced disease, Dr van Wamelen described how both levodopa and apomorphine are ‘old’ drugs currently undergoing reformulation for improved delivery and wider utility.
Professor Ray Chaudhuri argued that despite tremendous progress in our understanding of Parkinson’s, many challenges remain. These largely relate to the changes in the modern definition of Parkinson’s and how the condition is now regarded as having distinct syndromic presentations based on non-motor manifestations. Clinicians must be aware that ‘one size does NOT fit all’, and that consideration of the non-motor subtypes can guide decision making. For example, if a patient has cholinergic involvement, they should be counselled regarding cognitive decline, anticholinesterase inhibitors and gait training. Likewise, patients with presentations affecting sleep should consider avoiding agonists acting at D3 receptors (implicated in sudden onset sleep) and be given early advice on issues such as driving and working with machinery.
“Walking is part of being human” began Dr Emily Henderson who explained that although walking is often assumed to become an automatic movement, dual tasking experiments show that walking does require frontotemporal function. Both the nucleus basalis of Meynert and the pedunculopontine nucleus undergo degeneration in Parkinson’s, with more severe loss associated with cognitive impairment. Once gait is threatened, the brain has to use greater attentional resource, but this is difficult in the presence of a cholinergic deficit and can lead to problems such as falls. This has led to the hypothesis that improving cognition may prevent falls in people with Parkinson’s and Dr Henderson discussed the accumulating evidence for improved cognition as a therapeutic target for reduced falls.
Using case studies, Dr Ben Wright highlighted the often life-changing benefits that deep brain stimulation (DBS) can offer patients, but stressed that these benefits are only achieved in the ‘right’ patients. According to the updated NICE guidelines, DBS can be considered for people with advanced Parkinson’s whose symptoms are not adequately controlled by best medical therapy. However, even after decades of use, there remains a need for a better understanding of who to refer, when to refer them, and what benefits may be achieved, as well as an appreciation of the potential risks.
Closing with the controversial topic of neuroregeneration, Professor Roger Barker noted that this field of research is once again attracting investment. Attention had moved away from this approach in the face of famously failed trials, but Professor Barker suggested that the growth factor and stem cell trials may have been conducted too early – even before trying to understand the mechanisms of success in smaller studies. For example, clinical trials of growth factors have used suboptimal methods to deliver the treatment to the target site of action. While in some patients the effects of stem cell therapies were life changing, the clinical response varied from patient to patient. The challenge, therefore, is not whether this approach works, because it does in some patients, but rather how we can replicate this more consistently.