Parkinson’s disease is a neurodegenerative disorder that plagues more than 10 million people globally; in the United States alone, nearly 90,000 people are newly diagnosed every year. This debilitating disease manifests motor symptoms, such as tremors, involuntary movements (dyskinesia), and painful muscle contractions (dystonia), as well as non-motor symptoms, including cognitive impairment, dementia, and sleep disorders. These significantly degrade patients’ quality of life over time with disease progression. It is estimated that Parkinson’s costs the U.S. healthcare system approximately US$52 billion per year, when combining direct and indirect expenses such as lost income, social security payments, and treatment costs.

Despite the disease’s severity and widespread prevalence, the past few years have witnessed substantial advancements in clinical research related to Parkinson’s disease. In honor of the upcoming World Parkinson’s Day, held annually on April 11, this article spotlights five promising therapies on the horizon for these patients providing a glimmer of hope for achieving a world without Parkinson’s disease.

Read on to learn about the top five advances being supported by sponsors, contract research organizations (CROs), and researchers in Parkinson’s research! 

1. Deep Brain Stimulation (DBS) in Parkinson’s Disease

Deep brain stimulation (DBS) is the most important therapeutic advancement in Parkinson’s research since the emergence of levodopa, a synthetic analogue of dopamine that is currently a first-line therapy for Parkinson’s disease. DBS is a surgical therapy that involves the delivery of electrical stimulation to targeted areas of the brain that control movement, guided by magnetic resonance imaging (MRI) via a small, implanted device.

Although certainly more invasive than drug interventions for Parkinson’s disease, several studies have demonstrated DBS to successfully counteract the debilitating symptoms of the condition. Patients report experiencing an improved quality of life, bolstered by the advantages of the procedure over others like a thalamotomy or pallidotomy, including its reversibility and the minimal damage to surrounding nerve tissue. The benefits of DBS have been shown to last as long as five years, but it may also result in side effects such as dysphonia, depression and apathy, and personality changes.  

 

2. Clinical Research into New Levodopa Formulations

Recent advances in Parkinson’s research have brought considerable attention to the development of new forms of levodopa therapy. The focus of these clinical research advances has been to address the short half-life of levodopa and the resulting fluctuations in symptoms that patients with Parkinson’s disease experience.  

• Levodopa/carbidopa intestinal gel (LCIG) is continuously infused into the upper jejunum and has been shown to reduce off-times and extend symptom-free periods. 

• IPX066 is a sustained-release capsule preparation and maintains blood levodopa levels longer than immediate-release tablets.  

• CVT-301 is a levodopa inhalant being developed as a rescue medication during off-time, with studies showing rapid absorption and symptom improvement. 

• The Accordion Pill® capsule has a biodegradable polymeric film for gradual release. 

• ND0612 is a continuous subcutaneous levodopa injection being developed to reduce plasma concentration fluctuations. 

 

3. Alpha-Synuclein Targeting Immunotherapy

Alpha-synuclein (α-synuclein) is a protein that becomes misfolded and forms clumps in the brain in Parkinson’s disease, resulting in significant brain cell damage and triggering neurodegeneration. Given its critical role in the disease’s pathogenesis, Parkinson’s research is focused on advancing therapies targeting α-synuclein by developing passive and active immunization interventions, as well as protein aggregation modulators.

For example, PRX002 (prasinezumab) is a monoclonal antibody that is being used in passive immunization against aggregated α-synuclein. Clinical research into its safety and efficacy is being evaluated in the Phase 2 PASADENA and PADOVA clinical trials. On the other hand, PD01A is an active vaccine being developed against α-synuclein that has shown its safety and tolerability in early human trials. Lastly, inhibitors like NPT200-11, which prevents α-synuclein misfolding and aggregation, are also showing promise in experimental models to reduce α-synuclein pathology and associated neuroinflammation in Parkinson’s disease.

Visit this article from the TFS Intellect Hub to learn about how CROs tackle the unique complexities of inflammatory diseases like Parkinson’s. 

 

4. Stem Cell Therapy in Parkinson’s Research

Parkinson’s research is also exploring the therapeutic potential of stem cells in patients with this neurodegenerative disease, particularly those who exhibit resistance to existing treatment strategies. Although levodopa can relieve motor symptoms by boosting levels of dopamine, it does not address the underlying issue of progressive neuronal cell loss. Pluripotent stem cells (PSCs) offer exciting possibilities in cell transplantations because of their remarkable ability to differentiate into multiple types of cells, including dopaminergic neurons, in vitro and in vivo. Although fetal cell transplantation approaches date back to the 1990s, today’s PSC-based therapeutic methods offer novel advantages such as cellular reprogramming, utilizing PSCs with little to no graft rejection, and generating clinical-grade dopamine-producing neural cells (mDAPs) before transplantation to ensure their safety and efficacy.

In March 2024, the latest clinical research data on bemdaneprocel, a promising stem cell-derived treatment for Parkinson’s disease, indicated the drug continues to show positive results 18 months after treatment. Both low-dose and high-dose bemdaneprocel patient cohorts showed improvement in motor function tests. It was announced that these findings will be further tested in a Phase 2 clinical trial set to start later this year.  

 

5. Therapies Targeting Neuronal Rescue Pathways

As mentioned earlier, targeting α-synuclein misfolding is a critical component of understanding Parkinson’s disease pathophysiology and the neuronal cell loss it causes. Another promising avenue in Parkinson’s research is therapeutic targeting of the underlying neuronal pathways driving disease progression. One of these is neuroinflammation, a significant factor in the onset and worsening of Parkinson’s disease. For example, sargramostim is a modified recombinant human granulocyte-macrophage colony-stimulating factor that has shown potential for disease modification in mouse models. It was also found to be well-tolerated and effective at restoring immune homeostasis in patients with Parkinson’s disease following long-term treatment in a phase 1b clinical trial. Azathioprine is another anti-inflammatory agent that is being investigated in Parkinson’s research for its potential to slow disease progression.  

Another key neuronal pathway contributing to the loss of dopaminergic neurons in Parkinson’s disease is mitochondrial dysfunction. Dopamine-generating cells have high energy demands, which is supported by the mitochondria; however, when these organelles no longer function properly within a cell, neuronal death is the inevitable result. There is increasing evidence that boosting cellular levels of nicotinamide adenine dinucleotide (NAD), an important player in mitochondrial processes, may have neuroprotective effects, specifically through nicotinamide riboside (NR) therapy.

A Phase 1 trial reported that NR therapy was well-tolerated, led to a significant increase in cerebral NAD levels, and showed mild clinical improvement in patients with Parkinson’s disease. Other clinical research findings from the NR-SAFE safety trial also showed no moderate or severe adverse events and no signs of acute toxicity with NR therapy in these patients. 

 

Conclusion

In conclusion, Parkinson’s research is undergoing several advancements, with a range of promising innovations on the horizon, offering a beacon of hope for patients living with Parkinson’s disease. Although many of these therapies are still in the experimental stages and require further validation of their safety and efficacy, they hold immense potential to change the lives of millions of people. This upcoming World Parkinson’s Day (April 11), TFS HealthScience CRO invites you to celebrate the relentless efforts of researchers, sponsors, and CROs worldwide who are dedicated to finding a cure for Parkinson’s disease.  

 

Discover TFS HealthScience’s Neuroscience CRO

TFS HealthScience’s neuroscience services are dedicated to providing comprehensive support for your clinical trials, whether they’re local or global. With a proven track record of nearly 150 studies in neurology, psychiatry, and pain, and over 50 ongoing projects, we’re committed to delivering solutions that match your needs. Our global operations teams are specialized in neurology, offering rigorous operational oversight and adherence to global standards under the strong leadership of Anne Marie Nagy, Ph.D., who was named one of our top 10 influential women in clinical research as the Vice President, Head of Internal Medicine & Neuroscience at TFS.

Visit the TFS Neuroscience CRO website to learn more or connect with a TFS representative here!