What is Parkinson's Disease (PD)?

From the Guidelines

Parkinsonian syndromes, including Parkinson's disease, should be initially evaluated with a thorough clinical assessment, and imaging should be used as an essential diagnostic tool to support the diagnosis, as stated in the 2020 study by the Journal of the American College of Radiology 1. When diagnosing Parkinsonian syndromes, it is crucial to consider the various causes, including Parkinson's disease, progressive supranuclear palsy, multiple system atrophy, corticobasal degeneration, and vascular Parkinsonism.

• The clinical presentation of Parkinson's disease is characterized by resting tremor, bradykinesia, and rigidity, related to progressive degeneration of the dopaminergic neurons in the substantia nigra projecting to the striatum, as noted in the study 1.
• Other features of Parkinson's disease include autonomic dysfunction, behavioral changes, and dementia, which can impact the patient's quality of life and mortality.
• The study highlights that correctly diagnosing a Parkinsonian syndrome on clinical features alone can be challenging, and imaging remains an essential diagnostic tool in the evaluation of a patient presenting with Parkinsonian symptoms 1.
• The estimated interval between initial loss of dopaminergic neurons and the appearance of symptoms is approximately 5 years, after approximately 40% to 50% of the dopaminergic neurons in the substantia nigra have been lost, as mentioned in the study 1.
• The initial imaging evaluation for Parkinsonian syndromes should be guided by the clinical presentation and should aim to support the diagnosis and rule out other potential causes, as recommended by the 2020 study 1.

From the Research

Parkinson's Disease Treatment

• Parkinson's disease (PD) is a neurodegenerative disorder with a prevalence increasing with age, involving oxidative stress and glutamate toxicity in its pathomechanism 2
• Monoamine oxidase B (MAO-B) inhibitors have a favorable pharmacokinetic profile, improve the dopamine deficient state, and may have neuroprotective properties, making them valuable drugs in the treatment of PD 2
• Levodopa is still the most effective medical therapy for the symptomatic treatment of PD, but long-term treatment is associated with undesirable side effects such as motor fluctuations and dyskinesias 3

MAO-B Inhibitors and Levodopa

• MAO-B inhibitors, such as rasagiline and safinamide, have been proven safe and effective when added to a dopamine agonist in early PD, and as add-on therapy to levodopa in advanced PD 2
• The combination of levodopa and MAO-B inhibitors can provide a more continuous dopamine substitution, ameliorating fluctuations of motor behavior and enhancing antioxidative defense and methylation capacity 4
• A large, open-label, pragmatic randomized trial found that initial treatment with levodopa provided better long-term control of symptoms and quality of life compared to dopamine agonists or MAO-B inhibitors, but with a higher risk of motor complications 5

New Treatment Options

• A novel once-daily combination of low-dose, extended-release formulations of pramipexole and rasagiline (P2B001) has entered clinical development, with the potential to provide greater efficacy and a better tolerability profile compared to higher dosage dopamine agonist monotherapy 6
• P2B001 may offer a new treatment option for PD, with a lower risk of motor complications compared to levodopa, and a more effective and tolerable alternative to dopamine agonist monotherapy 6