A new treatment is being made available on the NHS for Parkinson’s patients. It takes advantage of automatic drug administration systems, such as the ones seen in insulin pumps, and foslevodopa–foscarbidopa – a combination drug shown to improve motor function in many trials.
Parkinson’s disease is a progressive disease of the nervous system. It is characterised by the degradation of basal ganglia in the brain – a group of structures in the thalamus (the part of the brain responsible for relaying motor and sensory signals to the cerebral cortex) involved in the coordination of movement. As a result of this, Parkinson’s patients often exhibit symptoms that involve compromised movement such as shaking and tremors, limited mobility and stiffness. The disease can yield psychological symptoms as well, with depression, anxiety and memory problems being a few of many. Despite this, Parkinson’s disease does not seem to impact life expectancy.
The substantia nigra is an area of the basal ganglia 'circuit' which, when damaged, can lead to Parkinson's disease. In the brains of people with Parkinson’s, nerve cells in the substantia nigra degrade, leading to a reduction in dopamine production. Dopamine is a crucial neurotransmitter and hormone. It is used by the substantia nigra to communicate with the basal ganglia, in order to stimulate movement. If there is a lack of dopamine, there is a resulting loss of movement. So, dopamine regulation is important in the treatment of Parkinson’s.
Levodopa is the precursor to dopamine. Clinicians use it very commonly as a dopamine replacement in treating Parkinson’s disease. Unlike dopamine, levodopa can cross the blood brain barrier – an important barrier of cells that regulates what can and cannot enter the microenvironment of the central nervous system. Levodopa is converted to dopamine in the body and is most useful in the central nervous system, but can also be converted into dopamine in the peripheral nervous system. To increase dopamine concentration in the central nervous system, levodopa is often administered with drugs that prevent its conversion before passing through the blood brain barrier, hence why foscarbidopa is administered with foslevodopa in this combination drug.
Oral administration of these drugs is the typical and first course of treatment. Pills can be tailored both in dosage and in ‘release’ timescale. Patients typically begin on a small dose regimen – around 300 to 1200 milligrams a day, divided into 3 to 12 doses. Taking pills this often can pose a challenge and an annoyance for both patient and carer, especially if one of the ways the patient’s Parkinson's manifests itself is difficulty swallowing.
Subcutaneous administration (injection) of this particular medication was detailed in a double-blind, randomised clinical trial in December 2022. A collection of patients with levodopa-responsive, advanced Parkinson’s disease were randomly assigned into two, equally-sized groups. One group received the active drug subcutaneously (by injection) during a 24-hour, continuous infusion with a tandem, orally administered placebo, whereas the other group received the opposite: a subcutaneously administered placebo, with an immediate-release pill containing the active drug.
Results of the trial showed that the combination drug foslevodopa–foscarbidopa improved motor function, both in the “off-time” (when symptoms returned between drug administration) and “on-time” (when the symptoms are controlled). It was also shown to have a favourable benefit-risk profile, making the drug a promising option for Parkinson’s treatment.
The newest available form of administration under the NHS is known as Produodopa®, made by the Illinois-based pharmaceutical company AbbVie. This method works in a similar way to insulin pumps for type one diabetes patients. The wearable pump eliminates the need for patients to take multiple pills a day, beneficial to both patients and their carers. Machine-based treatment also eliminates human error; continuous, automatic infusion of the drug removes any issues that may arise when patients forget to take their medication orally.
With an estimated one in 37 people diagnosed with Parkinson’s in their lifetime, the search for easier treatment remains important. This new option demonstrates another method by which this debilitating disease can be managed, vastly increasing the quality of life for many Parkinson’s sufferers. This drug will be rolled-out on the NHS from 27 February 2024, with thousands expecting to benefit.