British broadcaster Jeremy Paxman has revealed he is one of more than 10 million people living with Parkinson’s disease worldwide. It is the fastest growing neurological condition in terms of diagnosis and cases that lead to disability and death.
Although there is no cure yet, treatments for the disease have come a long way since it was first discovered over 200 years ago. People with Parkinson’s don’t have enough of the chemical dopamine, because some of the nerve cells that make it have died. Dopamine allows messages to be sent to the parts of the brain that co-ordinate movement.
We like to think of the management of Parkinson’s as a table that rests on four legs. There are drugs that replace the missing dopamine or mimic its effects; there is deep brain surgery; lots of different kinds of care; and then there is the importance of keeping patients and their families well informed and engaged.
Parkinson’s results from the deterioration of neurons in a part of the brain called the basal ganglia – a group of nuclei deep beneath the cerebral cortex (or outer layer of the brain). These neurons are responsible for processing information on movement and fine tuning activity as well as in a variety of cognitive and emotional functions.
A reduction in dopamine causes a variety of motor symptoms including tremors, rigid limbs and a general slowing of movement. Dopamine deficiency also leads to a wide range of non-motor symptoms – which may be less visible but are still severely debilitating – such as cognitive decline, depression, pain, urinary incontinence and constipation.
The history of Parkinson’s
Though Parkinson was the first to describe the disease in modern medicine, Charcot and his colleagues revolutionised treatments in the mid-19th century.. Parkinson was a proponent of blood-letting from the neck, in a bid to siphon off inflammatory pathogens and prevent them from reaching the brain. But Charcot and his colleagues favoured pharmaceutical approaches centred around anticholinergic drugs, which block the action of a neurotransmitter called acetylcholine. Anticholinergics are still in use today.
Around the same time, a host of other treatments were being explored at a hospital in Paris. Hyoscyamine, a plant-derived medication, was put in bread and fed to patients. Other medications, such as a derivative of quinine, were mixed with a syrup of orange rinds.
Charcot also claimed to see the symptoms of patients with Parkinson’s improving when travelling by train and horse-carriage. He became a proponent of vibration therapy, where patients’ bodies and heads were shaken vigorously by a rigged motor.
Modern treatments can be divided into pharmaceutical and surgical interventions, as well as a wide range of non-pharmacological interventions.
One of these, known as dopamine therapy, includes the mainstay drug levodopa. These drugs provide an external source of dopamine, acting as a replacement in depleted areas. Another type, called dopamine agonists, mimic the action of dopamine. This allows neurons to maintain communication.
Other types of drugs try to fight the source of the problem, either by preventing the breakdown of dopamine or by increasing its production.
Surgery for Parkinson’s, and a host of additional neurological conditions, was popularised at the start of the 20th century. Surgery involved either removing an area of the brain – such as the cerebral cortex – or electrically ablating (using electricity to create targeted burns in specific areas of the brain) other areas. In the 1940s, these kinds of procedures were the primary evidence used to pinpoint the exact location of the disease – the basal ganglia.
Modern surgical techniques, such as deep brain stimulation, target the same area.
Thin wires are threaded deep into the brain, with the tips placed in specific regions of the basal ganglia. The wires are manoeuvred around the exterior of the skull and weaved under the muscles of the neck into a pacemaker-like generator box sitting under the skin in the upper chest.
Wireless control of the generator allows pulses of electricity to be delivered to the part of the brain where the disease occurs. Similarly to a heart pacemaker, these electrical pulses are used to regulate brain activity. Surgery like this provides symptomatic relief, but doesn’t stop disease progression.
Many studies are underway to find new therapies. A variety of medications are being tested, from stem cell treatments to probiotics and some are even testing the potential to use hypoxia – limiting people’s oxygen levels.
Many new trials are focusing on a specific protein, called alpha-synuclein, which is affected by the deterioration of the neurons that causes Parkinson’s. The hope is that targeting the protein could halt the progression of disease.
Stimulation techniques using vibrations are beginning to make a comeback in modern medicine too, although the evidence to support them is still in its early days.
Recent research has shown exercise can help to suppress the motor symptoms of Parkinson’s disease, much like a drug. There’s some initial evidence to suggest it may even help to slow down the progression of Parkinson’s.
People are beginning to acknowledge the importance of a holistic approach, by focusing on treating the patient themselves and not just the disease. Such treatments involve physical, speech and cognitive behavioural therapies. Though these therapies don’t alter the disease progression, by targeting symptoms specific to patients, they can substantially increase their quality of life.
Professor Antoniades is the head of the NeuroMetrology group at the division in clinical neurology, Nuffield Department of Clinical Neurosciences, at the University of Oxford. She receives funding from various sources including project grants from NIHR, Wellcome Trust, UCB, Merck, EU collaborative grant and the University of Oxford. Prof Antoniades leads the OxQUIP trial and the digital phenotyping development for telemedicine and home monitoring. Prof Antoniades does not hold any stocks or stock options with any companies that are connected to Parkinson's disease or to any of the topics in this paper.
Prof. Bloem currently serves as co-Editor in Chief for the Journal of Parkinson’s disease, serves on the editorial board of Practical Neurology and Digital Biomarkers, has received honoraria from serving on the scientific advisory board for Abbvie, Biogen and UCB, has received fees for speaking at conferences from AbbVie, Zambon, Roche, GE Healthcare and Bial, and has received research support from the Netherlands Organization for Scientific Research, the Michael J Fox Foundation, UCB, Abbvie, the Stichting Parkinson Fonds, the Hersenstichting Nederland, the Parkinson’s Foundation, Verily Life Sciences, Horizon 2020 and the Parkinson Vereniging. Prof. Bloem does not hold any stocks or stock options with any companies that are connected to Parkinson's disease or to any of the topics in this paper.
Salil Patel does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.