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Produodopa: A Breakthrough Treatment for Parkinson’s

5th March 2024

By Dan Birkinshaw, science writer.

Parkinson’s is a neurological condition that affects approximately 6.1 million people globally [1], with 153,000 of those being in the UK. People living with Parkinson’s can experience a combination of over 40 different symptoms, but each case is unique and no one patient responds the same to every available treatment [2]. However, there is a new treatment that has been approved for use by the NHS and is due to be rolled out by the end of this month: Produodopa. This therapy combines two existing drugs in an automatic pump to administer 24hr relief from symptoms and may prove to be a game-changing option for improving the lives of thousands of people living with Parkinson’s [1].

Produodopa: A Breakthrough Treatment for Parkinson’s

The Human Cost of Parkinson’s

The impact of Parkinson’s on those living with the condition and those it affects, such as their family, friends, and carers, cannot be overstated. In the UK, the majority of patients are over 50 years old, and most of these people are 70-79 years old. Although symptoms tend to first present later in life, approximately 1.2% of cases are early onset in the under-50s age group [2]. In all cases, the patient’s quality of life is greatly affected.

Parkinson’s can be divided into several different types, the three most common being [3]:

Idiopathic Parkinson’s affects the majority of cases, with symptoms including tremors, rigidity (including facial masking), and slowness of movement (bradykinesia). Idiopathic cases present with no known cause.

Vascular parkinsonism is caused by restricted blood flow to the brain, such as in the aftermath of a stroke, and presents with problems with memory, sleep, mood, and movement. Mood problems can include depression and anxiety, hallucinations, and dementia. And these symptoms may also be brought on by the stress of diagnosis or of living with Parkinson’s.

Drug-induced parkinsonism can be caused by drugs that block the neurotransmitter action of dopamine (neuroleptic drugs), such as those used to treat schizophrenia and other psychotic disorders. However, the symptoms of this form of Parkinson’s do not progressively worsen as with thee other forms, and most patients recover within a period of days-months after stopping the treatment.

As well as the neurological impact of Parkinson’s, the condition is also associated with gastrointestinal issues in 80% of patients, which are often experienced several years prior to formal diagnosis. You can read our previous blog post on neurological diseases and the gut-brain axis for more information on this relationship.

Existing Therapies for Parkinson’s

There is as yet no available cure for Parkinson’s, but there are many therapeutic medicines and procedures in use around the world to alleviate its symptoms. It is important to note that because the exact mechanisms that cause Parkinson’s are unknown, therapies are focused on alleviation of its symptoms and their causes. And, in turn, as the majority of cases of Parkinson’s involve some combination of motor function symptoms, treatments are predominantly focused on alleviating these symptoms above others [4].

A broad range of neuroprotective drugs can be used to combat the neurodegeneration associated with Parkinson’s, but developing these drugs is a challenging process. The pathogenesis of Parkinson’s is elusive and there is a lack of sensitive and reliable biomarkers that can be used to monitor the condition’s progress. Because the symptomatic progression and severity of Parkinson’s varies from patient to patient, it is difficult to implement a homogeneous approach to its treatment [5].

Existing treatments for Parkinson’s can be categorized as drug therapy, surgical intervention, or behavioural therapy, and these categories contain a host of different approaches [4]:

Existing treatments for Parkinson’s can be categorized as drug therapy, surgical intervention, or behavioural therapy, and these categories contain a host of different approaches

Although these treatments have the potential to be effective, the heterogeneous nature of Parkinson’s presentation means that a combination of these therapies may be needed to meet individual patient needs. Symptoms also tend to worsen progressively throughout the day, so therapies need to account for this. Additionally, while drug-based therapies, such as L-DOPA, are effective in 80% of cases, many patients need to take over 20 pills per day to reduce the severity of their symptoms, and the effects can be inconsistent. This is especially noticeable overnight, when the effects of the drugs are reduced as patients cannot take them while asleep [6]. Another drawback to more traditional oral drug-based therapies is that they depreciate in effectiveness over time, eventually providing no relief from symptoms.

Produodopa aims to overcome some of these drawbacks.

Produodopa – A New Approach

So how does produodopa work, and just how much of a game-changer will it be?

Produodopa is a combination of two drugs, foslevodopa and foscarbidopa, and is administered via a small automatic pump that delivers a continuous dose of the medication, 24 hours a day. Patients can also administer ‘top up’ doses when required. Although some other treatments are administered in a similar manner, such as apomorphine (which mimics dopamine and is also administered via injection), this is the first treatment that provides patients with round-the-clock relief from the motor symptoms of Parkinson’s [7].

The drug therapy itself works by converting foslevodopa into the neurotransmitter dopamine, improving signal transmission in the brain and thereby nervous control of movements. Foscarbidopa, meanwhile, acts outside the brain to prevent metabolism of foslevodopa so that more can be taken up by the central nervous system (CNS) [8].

The National Institute for Health and Care Excellence (NICE) first approved produodopa for use on October 26th, 2023. Manufactured by AbbVie, the drug and pump used for administration make the process much more convenient for patients and carers than previous drug therapies [9]. Benefits of this new therapy include reduced dyskinesia, better sleep quality, improved overnight motor control, and more relaxed wake-ups with reduced dyskinesia and improved mobility. This brings the overall benefit of improved quality of life, with only mild to moderate side effects which mostly resolve spontaneously without the need for clinical intervention [10].

There’s Hope for the Future

Although Parkinson’s has no known cure, the future is looking brighter in terms of therapies to alleviate its symptoms. Research into transplantation and gene therapy techniques shows great promise, and the arrival of produodopa for round-the-clock relief from motor symptoms will allow patients a greatly improved quality of life.

Where standard oral medications no longer work, produodopa has been shown to bring great benefit in clinical trials.

And although the initial impact of this treatment technique may be small, for those it helps, the effect will be profound and life-altering. We may eventually see more widespread use of produodopa to treat Parkinson’s, and hopefully more patients will soon experience a lessening of their symptoms, and an improved quality of life.

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[References]

1.AbbVie Launches PRODUODOPA® (foslevodopa/foscarbidopa) for People Living with Advanced Parkinson’s Disease in the European Union. (2024, January 9th). Abbvie. https://news.abbvie.com/2024-01-09-AbbVie-Launches-PRODUODOPA-R-foslevodopa-foscarbidopa-for-People-Living-with-Advanced-Parkinsons-Disease-in-the-European-Union

2.Reporting on Parkinson’s: information for journalists. (2023, September 6th). Parkinson’s UK. https://www.parkinsons.org.uk/about-us/reporting-parkinsons-information-journalists

3.Types of Parkinsonism. (2023, September 11th). Parkinson’s UK) https://www.parkinsons.org.uk/information-and-support/types-parkinsonism

4.Lee, T. K. and Yankee, E. L. 2020. A review on Parkinson’s disease treatment. Neuroimmunology and Neuroinflammation, 8, 222-244

5.Jankovic, J. and Tan, E. K. 2020. Parkinson’s disease: etiopathogenesis and treatment. Journal of Neurology, Neurosurgery & Psychiatry, 91(8), 795-808

6.New Parkinson’s drug Produodopa to be available on NHS. (2024, February 17th). BBC News. https://www.bbc.co.uk/news/health-68316877

7.New treatment for Parkinson’s approved by NICE (The National Institute for Health and Care Excellence). (2023, October 26th). Parkinson’s UK. https://www.parkinsons.org.uk/news/new-treatment-parkinsons-approved-nice-national-institute-health-and-care-excellence

8.Greig, S. L. and McKeage, K. 2016. Carbidopa/Levodopa ER Capsules (Rytary(®), Numient™): A Review in Parkinson’s Disease. CNS Drugs, 30(1), 79-90

9.First NICE-recommended treatment for Parkinson’s set to benefit hundreds. (2023, October 26th). National Institute for Health and Care Excellence. https://www.nice.org.uk/news/article/first-nice-recommended-treatment-for-parkinson-s-set-to-benefit-hundreds

10.Ayazpoor, U. 2023. Continuous effective levels with subcutaneous levodopa. Info Neurology and Psychiatry, 25(54), https://doi.org/10.1007/s15005-023-3502-6

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