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Significant Patient Need in Advanced Parkinson’s Disease

Parkinson’s disease is the second most common neurodegenerative disorder, after Alzheimer’s disease, affecting nearly one million people in the United States.

Parkinson’s disease (PD) is a progressive disorder characterized by a diminished production of dopamine in a specific area of the brain called substantia nigra. According to the Parkinson's Foundation, PD is the second most common neurodegenerative disorder, after Alzheimer's disease, affecting nearly one million people in the United States. This number is expected to rise to 1.2 million by 2030. Incidence of the disease increases with age, but an estimated four percent of people with PD are diagnosed before age 50. Men are 1.5 times more likely to have Parkinson's than women. The estimated healthcare costs related to the disease in the U.S. alone, including treatment, social security payments and lost income, are nearly $52 billion per year.


Symptoms of PD involve movement (motor) and non-movement (non-motor) disability such as bradykinesia (slow movement), tremor, rigidity (stiffness), postural instability, depression and sleep disturbance. These symptoms generally develop slowly over years and vary by individual eventually becoming more severe over time, creating a complex clinical picture.

Disease Progression Occurs Over Time

Though PD remains largely idiopathic, increasing evidence from recent studies suggest a possible linkage between the gut (the gastrointestinal system) and PD. The current theory (part of Braak's hypothesis) is that accumulation in the brain of the protein alpha-synuclein -- a hallmark of the disease -- occurs in nerve cells of the olfactory bulb, which controls sense of smell, and the medulla in the brainstem. With disease progression, the protein aggregates also develop in the substantia nigra and the cortex over time. Under the Braak theory, the protein aggregation could begin in the nervous system of the gastrointestinal tract and migrate to the central nervous system.


There are different stages of PD defined by typical patterns of progression and the severity of symptoms over the years. Not everyone will experience all the symptoms of the disease nor will they experience them in the same order or level of intensity.

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Anticipated U.S. Population affected by Parkinson's  Disease by 2030


Approximately 150,000 Americans Living with Advanced Parkinson's Disease


Estimated Annual Healthcare Costs Related to Parkinson's Disease

Advanced Parkinson's Disease

Most people living with PD will eventually progress to the advanced stage (APD). It is estimated that approximately 15 percent of the nearly one million people living with the disease have APD.


With the disease progression, it becomes increasingly difficult to counteract PD symptoms and side effects despite combinations of oral treatments, including levodopa. In the advanced stages, gastrointestinal dysfunction with erratic gastric emptying, protein binding effect, short half-life of levodopa and a narrowing of the therapeutic window eventually result in a compromised quality of life due to significant amount of waking hours spent in the highly disabling state of hypo- and hyperkinetic states (“On-Off” fluctuations). Such fluctuation results in complications that can be a major source of distress, disability and are difficult to treat.


“On-off” fluctuations are sudden, unpredictable shifts between “well-” or “over-” treated status (“On”) and an undertreated state with severe symptoms of parkinsonism (“Off”). Reducing “Off” periods is important as this is the biggest contributor to functional impairment in individuals with APD. Therefore, a major goal in the treatment of APD is to provide continuous or continuous-like dopaminergic stimulation (CDS) in order to restore or maintain physical and cognitive functions.

Available Treatment Options for Advanced Parkinson's Disease

While available oral treatments for patients with intermediate stages of the disease have some limitations, the available treatments for patients with APD are even more restricted. They consist of highly complex combinations of anti-Parkinsonian medications and/or interventional therapies aimed at treating the symptoms. 

Despite the availability of several classes of anti-Parkinsonian medications to manage the motor and non-motor deficits, oral levodopa remains the mainstay of treatment.

Oral Treatment

The treatment regimen with an oral medication for APD, such as levodopa, is complex requiring multiple medications upwards of 10 pills per day, and the therapeutic window gradually becomes narrower as the response to each oral levodopa dose gets shorter with disease progression. Additionally, while levodopa replenishes dopamine levels in the brain, it comes with side effects, impacting the brain and nervous system, and further worsens gastrointestinal dysfunction with erratic gastric emptying. Due to the gastrointestinal stress, alternative routes of administration to bypass the stomach often need to be considered.


Device Therapies

Device-assisted therapies that bypass the gastrointestinal system and allow for continuous dopaminergic stimulation are often considered for APD patients in whom oral medications no longer offer adequate relief of their Parkinsonian symptoms. As healthcare providers and patients have become more familiar with device-assisted therapies, such as levodopa–carbidopa intestinal gel infusion, apomorphine infusion (approved in Europe), and Deep Brain Stimulation, utilization has grown significantly due to their ability to address the limitations of oral medications and the desired therapeutic activity for the APD patient.


  1. Varanese, et al. Treatment of Advanced Parkinson’s Disease. Parkinson’s Disease, 2010:480260

  2. Parkinson’s Foundation. Accessed August 31, 2021.

  3. Öthman M, Widman E, Nygren I, Nyholm D. Initial Experience of the Levodopa–Entacapone–Carbidopa Intestinal Gel in Clinical Practice. Journal of Personalized Medicine. 2021; 11(4):254.

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