Parkinson's Disease Research

Parkinson's disease (PD) is a chronic, progressive neurodegenerative disorder that affects movement and often leads to cognitive and behavioral changes. It is the second most common neurodegenerative disease after Alzheimer's disease. PD is caused by the loss of neurons capable of producing dopamine, a neurotransmitter that plays a crucial role in regulating movement, coordination, and balance. As these neurons die, dopamine levels decline, leading to the characteristic motor symptoms of PD. While PD is not yet curable, several drug types have been found that reduce its symptoms. Many researchers are investigating the underlying mechanisms of the disease and searching for new therapeutic targets.

Image Credit: Naeblys/Shutterstock.com

Image Credit: Naeblys/Shutterstock.com

The hottest topics in PD include biomarker development, stem cell therapy, gene therapy, neuroprotective treatments, nutritional approaches, and beyond.

Biomarker development

Currently, PD diagnosis relies primarily on clinical assessment of motor symptoms, which often appear when a significant portion of dopamine-producing neurons have already been lost. This delay in diagnosis can hinder early intervention and personalized treatment strategies. Researchers are developing biomarkers, such as blood or cerebrospinal fluid tests, to diagnose PD earlier and track disease progression more accurately. Early diagnosis and monitoring are crucial for timely intervention and personalized treatment strategies.

Several potential types of biomarkers for PD are under investigation, including:

  • Alpha-synuclein is an essential protein involved in PD pathology, and its misfolded forms can be detected in cerebrospinal fluid (CSF) or blood samples. Researchers are identifying new molecular drug targets, including proteins involved in alpha-synuclein aggregation. These novel targets could lead to more effective and disease-modifying therapies.
  • Imaging techniques scans can reveal changes in brain structure and function that may indicate PD.
  • Genetic testing can identify mutations associated with increased PD risk, although genetic factors play a role in a minority of cases.
  • Omics technologies, such as proteomics and metabolomics, can provide a comprehensive profile of PD-associated molecular changes.

Stem cell therapy 

Recent progress in developmental and stem cell biology research has paved the way for cell-replacement therapies involving dopamine neurons derived from human pluripotent stem cells. Additionally, researchers led by a team at the University of Edinburgh have successfully used skin samples from a patient to create brain nerve cells. By studying patient-derived nerve cells, scientists can gain deeper insights into the cellular and molecular processes contributing to neuronal death in PD. These nerve cells provide a valuable platform for testing new drugs aimed at slowing the progression of Parkinson's disease. By observing how drugs affect the nerve cells, researchers can assess their efficacy and safety before moving to clinical trials.

Gene therapy

Much research has been done to identify the genes that can raise the risk of developing PD. In a large genetic study, five new common risk genes have been discovered, bringing the total number of known genetic susceptibility genes to 11. The researchers found that any of these specific genes increased the risk of developing PD by 2.5 times. Assuming a prevalence of PD of 0.14% in the general population, the risk would increase to 0.35% in the highest-risk group.

Yet another study by US researchers suggests that the immune system may play a critical role in the development of PD. In their 20-year study of 4,000 people, half with PD, researchers found an association between genes that control immunity and the diseased condition.

A clinical trial by US researchers has shown promising results for gene therapy in PD. This study, published in The Lancet Neurology, used a viral vector to deliver genes to brain cells. This resulted in improvement in symptoms in half of the patients.

The proposed viral vector-based gene therapy involved using a non-infectious virus to carry a gene into a part of the brain called the subthalamic nucleus (STN). This gene produces an enzyme called glutamic acid decarboxylase (GAD). This enzyme catalyzes the production of a neurotransmitter called GABA. GABA acts as a direct inhibitor of the overactive cells in the STN. People with PD have reduced levels of GABA in their STN.

Neuroprotective treatments

Neuroprotective treatments have been extensively investigated over the last decades. These agents could protect neurons from cell death and slow the progression of the disease. Agents currently under investigation as neuroprotective agents include anti-apoptotic drugs (CEP 1347 and CTCT346), lazaroids, bioenergetics, and antiglutamatergic agents.

Other neuroprotective agents that have been used include the monoamine oxidase inhibitors selegiline and rasagiline, dopamine agonists, and the complex I fortifier coenzyme Q10.

Nutrition and further approaches

Nutrients have been investigated in clinical trials for patients with PD. The L-dopa precursor L-tyrosine has been shown to relieve an average of 70% of symptoms. Ferrous iron, an essential cofactor for L-dopa biosynthesis, reduced symptoms between 10% and 60% in some patients. Efficacy has also been noted with tetrahydrofolate  (THFA), nicotinamide adenine dinucleotide (NADH), and pyridoxine—coenzymes and coenzyme precursors involved in dopamine biosynthesis.

Research has shown that people who take ibuprofen regularly have a lower risk of developing PD. In studies of more than 135,000 men and women, regular ibuprofen intake was 40% less likely to develop PD. However, like all NSAIDs, ibuprofen can cause concerning side effects, such as an increased risk of gastrointestinal bleeding.

Personalized medicine

Personalized medicine is gaining traction in PD research. This approach involves tailoring treatment strategies based on an individual's genetic profile, disease stage, and symptom severity, leading to more effective and individualized care. While personalized medicine in PD is still in its early stages, it holds great promise for improving treatment outcomes and quality of life for individuals with this complex neurodegenerative disorder. As research advances and technologies evolve, personalized medicine approaches are poised to transform PD care and provide patients with more effective and individualized treatment options.

Deep brain stimulation (DBS) is a surgical therapy for treating specific aspects of PD. It involves implanting a device that delivers electrical impulses to specific areas of the brain that control movement. These electrical signals help to regulate abnormal brain activity and improve motor symptoms associated with PD, such as tremors, stiffness, slowness of movement, and gait issues.

Original Sources

  1. http://www.nhs.uk/conditions/Parkinsons-disease/Pages/Introduction.aspx
  2. https://www.parkinson.org/
  3. http://www.ninds.nih.gov/research/parkinsonsweb/index.htm
  4. http://www.parkinsons.org.uk/research.aspx

References

Further Reading

Article Revisions

  • Jul 10 2024 - References added for the new information included.
  • Jul 10 2024 - Body improved for spelling, punctuation, grammar, and readability, as well as the providing the most up to date information. Two new sections added to reflect progress of field since original publication.
  • Jul 10 2024 - Image added.

Last Updated: Jul 10, 2024

Dr. Luis Vaschetto

Written by

Dr. Luis Vaschetto

After completing his Bachelor of Science in Genetics in 2011, Luis continued his studies to complete his Ph.D. in Biological Sciences in March of 2016. During his Ph.D., Luis explored how the last glaciations might have affected the population genetic structure of Geraecormobious Sylvarum (Opiliones-Arachnida), a subtropical harvestman inhabiting the Parana Forest and the Yungas Forest, two completely disjunct areas in northern Argentina.

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