"There are a number of new treatments in the pipeline and in development that might help to improve our current management of Parkinson's disease. Such new therapies are aimed at reducing progressive functional worsening over time. This is a major unmet need, but most difficult to obtain, as therapeutic targets are still not clearly identified and methods to demonstrate such an effect in patients are long and complex", Prof Olivier Rascol from the University Hospital Toulouse, France, Chair of the EAN Subspecialty Scientific Panel Movement Disorders, told the Congress of the European Academy of Neurology (EAN) in Berlin.
New hopes for disease modification
Around 1.2 million patients in the EU suffer from Parkinson's disease, and an estimated 7 to 10 million people worldwide. Although a broad range of treatments are available that offer symptomatic relief, there is currently still a lack of methods reversing the effects of the disease.
Neuroprotective interventions that would be able to modify the progression of Parkinson`s disease have stood out as a failed therapeutic goal over the last two decades, despite potentially encouraging results with compounds like rasagiline, according to Prof Rascol. "Newer molecular targets, new animal models, novel clinical trial designs, and biomarkers to assess disease modification, however, have created hope for future therapeutic interventions. Among the compounds which have been investigated in proof-of-concept studies are, for example, GLP-1 analogues or iron chelators."
New application forms for better motor symptom control
In parallel, new medications to better treat motor and non motor symptoms of Parkinsonian patients are in late stages of development, "which provides hopes for rapid benefit", as Prof Rascol pointed out. "Recent trials have documented a potential of novel levodopa-carbidopa formulations for the improved control of motor symptoms in PD. These include intrajejunal infusions, new extended-release applications, subcutaneous pump-patches or formulations for inhalative administration. New COMTinhibitors and MAO-B inhibitors such as opicapone or safinamide have been shown to improve 'off'-problems in PD patients."
As the expert reported, innovative non-dopaminergic drugs have been tested to manage motor fluctuations and dyskinesia, although trials testing compounds like adenosine A2A antagonists or MGluR5 modulators have not yet produced consistent positive results.
Improvement of non-motor symptoms
"For the first time, new randomized controlled trials have demonstrated that dopamine and non-dopaminergic drugs can improve non-motor parkinsonian symptoms," Prof Rascol said. This is of particular significance since non-motor symptoms, an intrinsic part of PD, have a major impact on quality of life.
Nocturnal sleep disturbance occurs in 60 to 98 per cent of PD patients and is often severe. Neuropsychiatric problems such as anxiety, dementia and gambling addiction are also common comorbidities. Anxiety and depression develop in about 60 percent of patients with PD; this is twice the rate seen in the general population. The severity of mood disturbance or apathy is an important determinant of quality of life in patients, often having a greater impact than motor impairment.
"The dopamine agonists pramipexole and piribedil have shown efficacy in treating PD-related depression or apathy; the opiate agonist oxycodone/naloxone has demonstrated potential to effectively control pain; and the 5HT2A inverse agonist pimavenserin seems to be able to positively influence hallucinations", Prof Rascol said. Importance of non-pharmacological interventions
Therapeutic advances are not only being made in the field of novel substances or new application forms, but also as regards non pharmacological interventions, Prof Rascol explained: "There is an important amount of research under way in order to better understand and characterize the importance of physiotherapy or various types of physical exercise to better manage PD. However, at the moment, the quality of such trials remained usually insufficient to provide indisputable robust evidence."