Chi-Ying Lin, MD, MPH, is researching how movement and non-movement symptoms intersect for people with Parkinson’s disease (PD) and Alzheimer’s disease. Through studying these symptoms in people with movement disorders and cognitive disorders, he hopes to learn more about what parts of the brain produce specific symptoms, which could lead to new treatments for people with Parkinson’s.

Following his Parkinson’s Foundation fellowship at Columbia University Irving Medical Center, Dr. Lin is now an assistant professor of neurology at Baylor College of Medicine with dual appointments in the Alzheimer’s Disease and Memory Disorders Center and the Parkinson’s Disease Center and Movement Disorders Clinic, which is a Parkinson’s Foundation Center of Excellence. We spoke to Dr. Lin to learn more about his work and what he finds most promising in current Parkinson’s research.

What led you to Parkinson’s research?

I was very interested in the personalization of Parkinson’s evaluation and treatment plans, and in learning more about how movement and cognitive symptoms intersect.

I came to the United States after my residency in Taiwan because I was interested in neuropathology at Columbia University. When I arrived, I had a chance to hear Dr. Stanley Fahn speak about movement disorders and it blew me away. I decided I wanted additional training in movement disorders. Because of the excellent clinical training and mentorship opportunities in the U.S., I decided to restart my career here, which led me to my residency at Mount Sinai and my fellowship at Columbia University Irving Medical Center, which was supported by the Parkinson’s Foundation.

Why research the intersection of movement disorders and cognitive disorders?

In my first exposure to cognitive disorders in Taiwan, I was not entirely aware that people with movement disorders actually have a lot of cognitive issues. At Columbia University, I learned through the Parkinson’s Foundation that around 50% of people with PD could have either mild cognitive impairment or dementia. I felt it was important to study this intersection, which is a relatively new field.

There is a brain region called the cerebellum that sits right behind the brainstem and above the neck. It used to be thought of as a pure motor organ and was often studied to understand movement. However, in the past 10 years, there has been an increased understanding that the cerebellum controls non-movement symptoms as well.

Can you tell us about your impulse control study?

In my fellowship, I conducted studies, and one primarily focused on the intersection of movement and cognitive disorders, especially for impulsivity and compulsivity, which are commonly seen in people with Parkinson’s. This study compared impulsivity in people with Parkinson’s to people with a different cognitive condition, Cerebellar Ataxia, which can include impulsive behavioral symptoms as well.

Our findings determined that impulsivity was different between the two conditions, and with Parkinson’s disease, it can be more widespread to include several impulsive behaviors that are both movement and non-movement related, including gambling, eating, hypersexuality, spending and compulsively taking medication. This suggests that that cerebellum and basal ganglia, a different part of the brain that is affected by PD, can produce different kinds of impulsive behaviors, furthering our understanding of how the cerebellum functions.

What are you currently researching?

The goal of my current study is to better understand the genetic and environmental factors that lead to Alzheimer’s or Parkinson’s in each participant.

I am on dual appointment in the Parkinson’s Center and Alzheimer’s Center. I’m also part of Baylor’s Precision Medicine Core, where I comprehensively study people with and without cognitive disorders and use clinical history, comprehensive assessments, neuroimaging and genome sequencing to characterize early cognitive impairments and determine the risk a person has for a cognitive disorder. Houston, TX, where Baylor is located, is the most racially and ethnically diverse city in the country, which makes it a great place for this study.

Furthering the work I did during my fellowship; I’m also conducting a functional neuroimaging project to identify the role of the cerebellum in both Alzheimer’s and Parkinson’s. Once we understand the role, we can consider treatments like deep brain stimulation to address impulsivity and compulsivity.

What gives you hope for the future of Parkinson’s research?

My overarching goal is to be part of the experts in the world that find the modifying therapy or, to be ambitious, the corrective therapy for Parkinson’s. Practically, I want to address the symptoms of Parkinson’s, which is why I’m focusing on the cerebellum and its impulsivity power to see if we can better address that symptom for people with Parkinson’s.

What do you see as the most promising recent discoveries in Parkinson’s research?

The Parkinson’s Foundation genetics study, PD GENEration, Mapping the Future of Parkinson’s Disease, is something that my patients and their families benefit from immensely because it not only includes genetic testing, but genetic counseling as well at no cost to participants. I’ve enrolled many patients into the study, and I think overall it will be a very fruitful study for Parkinson’s research.

I also believe the Parkinson’s Foundation study about alpha synuclein detection in stool is very interesting and could lead to earlier Parkinson’s disease detection. It interests me because it is noninvasive and could allow for early-stage study recruitment.

How has support from the Parkinson’s Foundation impacted your career?

My fellowship taught me that Parkinson’s does not look the same in every person, and care must be individualized. I’m so appreciative of the support I’ve received from the Parkinson’s Foundation.

There are not enough movement disorders specialists, especially in rural areas, and the Foundation’s support of expanding care for people with Parkinson’s is so important.

Because of the Parkinson’s Foundation, I was able to learn from well-respected movement disorders leaders and build upon my foundation as a movement disorders neurologist. I was lucky to be in the last fellowship class trained by Dr. Fahn before his retirement. He taught me how to be a very compassionate movement disorders neurologist who actively works with patients and their families to find the best treatment options.

For more information on our research grants, visit Parkinson.org/Grants.

A healthy immune system recognizes and fights off illness and disease. Inflammation is part of that process. However, if inflammation persists over long periods of time — which might be the case in Parkinson’s disease (PD) — it can begin to do more harm than good. New research suggests that inflammation may play a critical role when it comes to Parkinson’s.

Studies have shown that inflammation is linked to certain Parkinson’s symptoms and that people with Parkinson’s have markers of inflammation (certain proteins or chemicals that are associated with the inflammatory process) in their blood and cerebrospinal fluid. Moreover, research indicates that manipulating inflammation in an animal model of Parkinson’s resulted in damaging changes in the brain.

Many questions remain about the exact role and mechanisms of inflammation in Parkinson’s. Most importantly, scientists want to untangle whether inflammation plays a role in the onset of Parkinson’s, or whether it is a result of the disease. Another significant question is whether inflammation is associated with certain clinical features that could predict disease progression.

A new study published in Movement Disorders by Talene Yacoubian, MD, PhD, a neurologist at University of Alabama at Birmingham and a Parkinson’s Foundation Scientific Advisory Board member, and colleagues addresses some of these questions. Dr. Yacoubian and her team designed a clinical study to assess the presence of inflammation in those who were within two years of a Parkinson’s diagnosis — before starting medication that may lead to changes in inflammation.

The goal of the study was to determine whether inflammation is present early in Parkinson’s, and whether certain markers of inflammation were correlated to clinical features. The authors plan to follow the study participants to see how inflammation changes in individuals over time.

A total of 120 participants were enrolled in the study. Of those, 58 had Parkinson’s and 62 were healthy controls (did not have PD). Researchers collected blood from all participants to look for various markers of inflammation. A subset of participants also had cerebrospinal fluid samples collected and/or had regions of their brains imaged using a technique that is used for to analyze neuroinflammation.

Study Results

• Individuals with Parkinson’s showed significantly higher levels of brain inflammation than people without PD in several brain regions. This measure of brain inflammation was also correlated with other markers of inflammation in the blood and cerebrospinal fluid.

• Researchers looked at whether the brain imaging results were correlated with any clinical measure in participants with Parkinson’s. They found that inflammation in several brain regions was associated with worse visuospatial and cognitive scores.

What do these findings mean to the people with PD right now?

Currently, brain inflammation markers cannot be used to diagnose Parkinson’s or predict disease progression. Additionally, we do not yet know whether Parkinson’s medications have any impact on inflammation, nor do we yet know how inflammation changes over the course of the disease.

How are these findings important for the development of future treatments?

• Measures of inflammation may help predict cognitive decline. However, we need long-term studies designed to measure inflammatory signals and associated cognitive outcomes to better understand the relationship between these two processes.

• Long-term follow-up of study participants will be critical in understanding the significance of early inflammatory signals in Parkinson’s.

There are already multiple studies underway that further delve into inflammation and neurodegeneration. This research can ultimately lead to doctors being able to track inflammation to assess disease progression, and to the development of therapeutics that target inflammatory pathways in Parkinson’s.

Learn More

The Parkinson’s Foundation believes in empowering the Parkinson’s community through education. Learn more about PD and the topics in this article through our below resources, or by calling our free Helpline at 1-800-4PD-INFO (1-800-473-4636) for answers to your Parkinson’s questions.

• 6 Parkinson’s Virtual Biotech Drugs in Research & Development
• Simple Blood Draw Reveals Early Inflammation/Fatigue Connection
• Pain – This Parkinson’s symptom is directly related to inflammation.
• New to Parkinson’s

Every year, the Parkinson’s Foundation funds the most exciting and promising research ideas in the Parkinson’s disease (PD) field. In our latest Neuro Talk, Chief Scientific Officer James Beck, PhD, is joined by three researchers whose studies were funded by the Parkinson’s Foundation. Their projects, which range from investigating environmental factors to understanding cognition, explain how research is helping us further our understanding of Parkinson’s.

Watch the latest Parkinson’s disease videos on our YouTube channel.

The World Parkinson Congress is a unique conference that brings everyone in Parkinson’s disease (PD) community together — from people living with PD and their care partners, to healthcare professionals, researchers, and organizations working to make life better for people with Parkinson’s. This year, thousands attended the event dedicated to Parkinson’s research and care, in Barcelona, Spain, from July 4 to 7.

Below are the scientific posters the Parkinson’s Foundation presented at the sixth World Parkinson Congress:

Research Findings

These findings focus on how we can make PD research more inclusive and why it is essential to involve people with Parkinson’s in the research process.

SEE ALL RESEARCH POSTERS

1.  Characterizing the Frequency of Clinically Reportable Variants in Major Genes Established in Parkinson’s in a Large American Cohort

PD GENEration: Mapping the Future of Parkinson's Disease is research study that offers genetic testing and counseling, in English and Spanish, to people with Parkinson’s. This study aims to simplify access to clinical genetic testing to people with Parkinson’s and offer educational materials to clinicians on PD genetics, to help accelerate clinical trials in PD, improve PD care and research, and empower people with PD and their care teams.

Key Takeaways:

• The study has enrolled 10,510 participants, consisting of 58% males and 14.7% racially diverse participants.

• By providing genetic testing to all those interested and from all backgrounds, the study helps inform care, diversify the data, help engage people in research, and qualify more for enrollment in clinical trials for PD.

2.  Curation of Parkinson’s Genes Performed By An International Expert Panel: A ClinGen Initiative

With genetic testing for PD becoming more widely available due to studies such as PD GENEration, there is still no single definition of PD-related genes and genetic panels in the diagnostic setting. To address this, we formed the Parkinson´s Disease Gene Curation Expert Panel, recognized by ClinGen, with the mission of defining the clinical validity of gene-disease relationships for PD and atypical parkinsonism.

Key Takeaways:

• Our objective is to inaugurate an expert panel to assess the clinical validity of specific genes in association with PD. The council has published the clinical validity of these PD gene mutations: LRRK2, GBA1, PRKN, PINK1, SNCA, VPS35 and PARK7.

• This expert panel will help guide precision medicine efforts in PD and enable informed FDA decision-making in future therapeutic trials.

• The panel consists of 62 leaders worldwide representing different disciplines such as clinical neurology, genetics and molecular genomics.

3.  Building a Coalition to Advance Engagement of Black and African American Communities in PD Research

There is an underrepresentation of Black and African American communities in PD research. The Parkinson’s Foundation worked alongside Black and African American research advocates, clinicians, social workers, nurses and researchers to develop a coalition to learn more about, and respond to, the needs and priorities of these communities. 

Key Takeaways:

• This coalition will help to build relationships and allies to advance health equity research.

• The Parkinson’s Foundation will host a research advocate training, inviting 30 Black and African American research advocates to help drive research agendas/priorities and address research-related health disparities.

4.  Outcomes and Impact of Capacity Building for Patient Engagement in Research Through a Patient Advisory Board Model at Academic Research Centers

Involving people with Parkinson’s and care partners in the research process alongside scientists has gained traction. Despite this interest, research teams still seek training on methods and best practices for working alongside people with PD. Members of the Parkinson’s Foundation patient engagement team co-created a pilot training for staff of five academic research centers to create patient advisory boards and incorporate people with PD into the research process.

Key Takeaways:

• 83% of staff reported the patient advisory boards were beneficial to the organization’s research mission and will continue these meetings.

• The pilot training courses were generally successful in preparing staff to engage with participants in research through patient advisory boards.

• These practices and model can be a guideline for other academic research centers looking to engage people with PD in the research process.

Care Findings

These studies focus on how to improve care for people with Parkinson’s.

SEE ALL CARE POSTERS

5.  Optimizing Hospital Care for People with Parkinson’s: A new professional education course detailing best practices

Each year, more than 300,000 Americans with Parkinson’s receive care in the hospital. Data shows that people with PD are at increased risk for hospitalization and, once hospitalized, are more likely to have avoidable complications and poorer outcomes. To increase health care professionals’ understanding of these risks, with support from the CVS Health Foundation, we created a free accredited three-part course highlighting best practices in hospital settings. Learn more about staying safe when hospitalized.

• Course 1: Care in the Inpatient Setting

  Highlights the challenges commonly seen in the hospital and strategies that can help improve outcomes for people with Parkinson’s. Learn more.

• Course 2: Care in the Emergency Department

  People with PD visit the emergency department for many reasons, including falls. This course teaches optimal care strategies and how to mitigate risk. Learn more.

• Course 3: Care in the Outpatient Setting

  Addresses several safety risks when caring for a person with Parkinson’s who is undergoing an outpatient procedure. Learn more.

6.  Improving Parkinson’s Care in Senior Living Communities and Home Care Agencies in the U.S.

Community Partners in Parkinson’s Care has worked to provide staff education and resources to enhance staff knowledge and confidence in the provision of PD care. Training methods include site champion training, which provides an online curriculum. Outcomes including staff surveys and medication audits have been collected over time to assess awareness of PD care needs.  

Key Takeaways:

• 19,000+ health care professionals across many disciplines completed the online curriculum.

• Staff surveys have shown improvements in awareness of PD care needs following completion of the program’s online education curriculum. 

• Lessons learned include more education surrounding PD medication administration, including administering PD medications within 15 minutes of the scheduled time.

• These results indicate continued need of expanded programming for home care agencies and senior living communities to receive ongoing PD education at all sites.

7.   Pathway to Parkinson’s Foundation Exercise Education Accreditation Program & Competencies for Exercise Professionals

Exercise professionals play an important role in the care of people with Parkinson’s, but to date, there have been no unified guidelines or procedures in place to ensure that these professionals are competent to help people with PD. The Parkinson’s Foundation, in collaboration with psychometric methodologists, created a two-phase process to define competencies for exercise professionals and a framework for an accreditation program to recognize exercise education programs and courses.

Key Takeaways:

• Competencies allow for exercise professionals to describe the knowledge, skills, and abilities needed to provide optimal individual or group exercise sessions for individuals with Parkinson’s

• The Parkinson’s Foundation will accredit education programs and courses that provide the knowledge and skills necessary to create a safe and effective exercise experience for people with Parkinson’s.

8.  Utilizing the Parkinson’s Foundation Five Domains of Exercise Professional Competencies to Map Five Criteria for Exercise Education: A Pilot Study

The Parkinson’s Foundation sought to develop condition-specific competencies for exercise professionals (personal trainers and group exercise instructors) who work with people with Parkinson’s.

Key Takeaways:

• We developed a pilot accreditation process for Parkinson’s exercise education programs and continuing education courses to validate exercise competencies.
• The accreditation process accounts for the variety of exercise professionals (personal trainers, group exercise instructors, physical therapists, other healthcare professionals) who help people with PD.

Education Findings

These studies focus on trends in the Parkinson’s community and aim to provide information that can empower people in the PD community.

SEE ALL EDUCATION POSTERS

9.  Transforming Parkinson’s Education & Care in Underserved Populations: Engaging & Addressing American Indian and Alaskan Native Communities

Though there are many educational resources for Parkinson’s, very few address American Indian and Alaska Natives (AIAN) specifically. These populations have experienced historical trauma, systemic racism, and a lack of funding and access to health care services. We set out to understand how PD awareness and management is currently approached in tribal health clinics and Indian Health Services, worked to identify key partners and advisors, and to pilot outreach and education programming that reaches and engages AIAN populations and organizations.

Key Takeaways:

• A lack of PD information is available across tribal health organizations, demonstrating a need for more general outreach, basic education, and resource accessibility.

• These initial efforts will continue to advise upcoming Parkinson’s Foundation programming for AIAN populations and tribal public health organizations.

• The long-term goal is to create lasting partnerships and lines of communication to further develop responsive education and awareness initiatives.

10.  Caregiving Through the Progression: Themes from Parkinson’s Care Partners through early, mid-stage, and advanced Parkinson’s

The Parkinson’s Foundation conducted interviews with three Parkinson’s care partners for the Care Partner Program online course Caregiving Through the Progression. This poster highlights their unique experiences:

• Early Caregiving: Julia shares the turbulent road to her husband Phil’s diagnosis and her experience of Black cultural norms. She discusses these challenges, and how the strength of their core family provided unique support.

• Mid-stage Caregiving: Dick shares his experience as a male care partner expressing emotions in a healthy and productive way. He discusses how he prioritizes his spiritual and emotional wellness and how he and Chris prioritize communication.

• Advanced Caregiving: Edna shares the impact her husband Mark’s PD had on their daughters, who grew up with Parkinson’s as a part of their childhood. She discusses the cultural norms she experienced as a Filipino woman.

11.  Care Partners in Parkinson’s: Who calls the Parkinson’s Foundation Helpline and Why?

Our Helpline provides answers about PD, referrals to health professionals, support groups and wellness programs. This poster describes the reasons care partners contact the Helpline between 2016 to 2022.

Key Takeaways:

• The Helpline received 21,489 first-time callers and emailers where the gender of the person with Parkinson’s was known. 46% were cases with a spouse/partner and 33% were from an adult child.

• Nearly 81% of spouse/partner Helpline inquiries were regarding men with Parkinson's, despite men accounting for 60% of Parkinson's cases.

• Because male spouses/partners contact the Helpline less often than female, this study suggests a need for increased outreach toward male spouses/partners. This outreach could help male care partners gain information and resources to support their caregiving, and thus have a positive impact on the well-being of women with PD.

Stay up to date with the latest Parkinson’s Foundation programs, research and happenings in our Parkinson’s Today blog.

Living at Camp Lejeune, which had drinking water contaminated with tetrachloroethylene (PCE), is associated with an increased risk of developing Parkinson’s.

No one knows exactly what causes Parkinson's disease (PD), but scientists believe both genetic and environmental factors play essential roles. It is also not known why Parkinson’s cases appear to be on the rise. One theory is that industrial chemicals in the environment could contribute to diseases such as Parkinson’s, and new evidence supports this idea.

Recent studies have suggested that certain chemical pollutants could contribute to Parkinson’s. For instance, in rodents studies, when ingested, the industrial solvent trichloroethylene (TCE), a known human carcinogen, can cause brain damage and result in motor deficits. TCE does not occur naturally and is used in common household products, such as cleaning wipes and paint removers. Commercial dry cleaners also use the chemical. 

Additionally, one small study of twins in 2012 indicated that TCE was linked to a 6-fold increased risk of Parkinson’s. TCE and a similar chemical called tetrachloroethylene (PCE), a likely human carcinogen, are found in up to one-third of U.S. drinking water samples. However, only one small study had ever attempted to assess the risk of developing PD from these chemicals in drinking water.

In a new study published in JAMA Neurology, researchers analyzed the medical records of 84,824 veterans who were stationed at Camp Lejeune in Jacksonville, NC, in the 1980s. Camp Lejeune drinking water was contaminated with TCE, PCE, and several other volatile organic compounds (VOCs) from 1953 until 1987. Wells that provided water to the base were contaminated by sources found on the base, such as leaking underground storage tanks, industrial spills, and waste disposal sites (largely TCE) and an off-base dry-cleaning business (largely PCE). Median monthly levels of TCE in the base’s water supply were more than 70 times the permissible amount, the researchers noted in their new article.

Study Results

• The study compared the Camp Lejeune veterans’ records to those of more than 73,298 veterans stationed at Marine Corps Base Camp Pendleton in Oceanside, CA, which did not have contaminated drinking water. From the medical records, they found that 279 veterans from Camp Lejeune and 151 from Camp Pendleton had been diagnosed with Parkinson’s disease, for a prevalence of 0.33% and 0.21% respectively.
• Moreover, among those without a Parkinson’s diagnosis, there was a significant association of living at Camp Lejeune with diagnoses of anxiety, tremor or erectile dysfunction, all of which can be early signs of Parkinson’s.
• The study hypothesizes that TCE could be contributing to the more than doubling of Parkinson’s disease cases worldwide from 1990 to present.
• Overall, Camp Lejeune veterans who were exposed to drinking water contaminated with TCE and other chemicals had a 70% higher risk of developing Parkinson’s disease than Camp Pendleton veterans who were not exposed to contaminated water.

What does this mean?

TCE may contribute to risk of developing Parkinson’s. However, conclusions are still not definitive. The veterans who were stationed at Camp Lejeune may also have been exposed to other chemicals that could have contributed to Parkinson’s risk, such as vinyl chloride and benzene. Veterans could also have been exposed to other these or other chemicals before or after they were stationed at Camp Lejeune. More research is needed to determine whether exposure to TCE and/or other chemicals contributes to Parkinson’s risk.

What do these findings mean to the people with PD right now?

Even for people with Parkinson’s who had known exposure to TCE, it is still not conclusive that those chemicals caused the disease and/or are the sole cause of the disease.

Veterans with Parkinson’s who were stationed at Camp Lejeune for no less than 30 days between August 1, 1953, and December 31, 1987, may be eligible for additional benefits. Learn more on the VA webpage, Camp Lejeune: Past Water Contamination.

Learn More

The Parkinson’s Foundation believes in empowering the Parkinson’s community through education. Learn more about PD and the topics in this article through our below resources, or by calling our free Helpline at 1-800-4PD-INFO (1-800-473-4636) for answers to your Parkinson’s questions.

• Veterans & Parkinson’s
• Episode 122: Environmental Factors and Parkinson’s Disease
• Veterans Benefits

While still in the developmental stage, gene and cell-based therapies for people with Parkinson’s disease (PD) hold promise to improve quality of life. Learn how researchers hope these therapies might benefit symptom management and slow disease progression.

This article is based on Understanding Gene and Cell-Based Therapies in Parkinson's, a Parkinson’s Foundation Expert Briefing webinar presented by Roger Barker, PhD, Clinical Neuroscience Professor, John van Geest Centre for Brain Repair, University of Cambridge, U.K. Watch the webinar now.

Scientists studying potential gene and cell therapies for Parkinson’s base their work on the understanding that the disease stems from a genetic predisposition that impacts a protein found in brain cells called alpha-synuclein. In people with Parkinson’s, this protein builds up (or misfolds) into clusters called Lewy bodies. When Lewy bodies amass and spread, it leads to the death of dopamine-producing brain cells. Dopamine helps us move, balances moods and influences our emotional health. Once a significant number of these cells have died, a person begins to show the movement symptoms of Parkinson's, such as tremors, slowing and stiffening.

Current Parkinson’s therapies relieve symptoms by replacing lost dopamine through medication and disease management and lifestyle tools, such as exercise and complementary therapies.

New frontiers in PD therapy research include:

• Improved medications to target the dopamine system and treat dyskinesia (involuntary movements of the face, limbs or trunk) associated with levodopa use.
• Experimental closed-loop deep brain stimulation (DBS), in which a DBS system can learn what's happening in the brain and control stimulation applied to the brain to improve symptoms such as dyskinesia.
• Therapies targeting alpha-synuclein through reducing its production, slowing the build-up, or stopping the spread.

There are also various approaches within investigational gene and cell-based therapies targeting PD. Some of these aim to:

• replace lost dopamine
• rescue dying cells
• regrow dopamine-producing pathways

Ideally, a person with Parkinson’s could benefit from new therapies while still utilizing current treatment options. Each area of research — including those aimed at improving symptoms and gene therapies that seek to help the body help itself — tackles different factors of Parkinson’s. In the near future, a combination of cell and gene therapies along with pioneering medications, surgical advancements and lifestyle management might offer the most comprehensive therapy for people living with Parkinson's.

Examining PD Gene Therapy Approaches

Different companies are pursuing the potential behind various investigational therapies. At the forefront of research are approaches designed to:

1. Regrow the dopamine system. This method injects a gene intended to act as a growth factor, or fertilizer, to stimulate brains cells to regrow the dopamine system.
2. Replace lost dopamine. This method injects a gene that converts existing cells to produce dopamine. These could replace the need for dopamine-replacement medication.
3. Rescue dying cells. New research holds the potential to rescue dying cells, which could offer a path toward disease modification. This type of investigation is designed to interfere with PD and slow progression.

Though still experimental, different strategies have been taken to explore the above types of research over the past two decades with varying levels of success.

Research Aiming to Strengthen the Dopamine Pathway

In 1993, scientists made a pivotal discovery: glial cell line-derived neurotrophic factor (GDNF) — a protein that supports neurons (nerve cells in the brain) — is extremely powerful at regrowing dopamine nerve cells in a lab environment. This led to clinical trials where GDNF was infused into people's brains to try to regrow the dopamine system. The results of these trials are complex, and it is still unclear whether the therapy works.

Another gene therapy program that worked on the same principle was linked to those studies. The program connected neurturin protein (a similar substance to GDNF, though not as powerful) to the AAV2 gene. The investigation studied whether injecting the AAV2-neurturin gene into the area of the brain where dopamine is released would spur cells to take up the gene and promote dopamine fiber growth.

The AAV2-neurturin study went to a double-blind, placebo-controlled trial (participants were randomized, some receiving the treatment while others received a placebo). The study found that:

• At 12 months, there was no difference between those who received neurturin therapy and those who did not.
• At the end of 18 months, people who received the treatment seemed to be doing slightly better, leading investigators to think a successful trial needed more time.

In its second trial, AAV2-neurturin gene was injected into two sites in the brain. After two years, the study showed no therapeutic difference between the trial and placebo groups.

After the GDNF and AAV2-neurturin gene therapies trials, researchers came together to identify what they learned. They concluded such therapies held promise, but recommended future studies take place earlier in the course of Parkinson’s. In the first 1 to 3 years of diagnosis, a person still has several functioning dopamine fibers. These decline rapidly after the first three years. By 5 to 15 years post-diagnosis (the stage most previous trial participants were in) there are few dopamine fibers left.

Today, companies moving GDNF gene therapy trials forward include uniQure and Bayer. Though not gene therapy, Parkinson's UK is pursuing the potential benefits of a protein infusion to boost GDNF levels in the brain.

Can we spur non-nerve cells to make dopamine?

Another PD gene therapy approach is to attempt to infect certain non-nerve brain cells to give them the capacity to make dopamine. There are two main approaches:

• Inject cells to create a synthetic pathway for dopamine in its entirety.
• Give someone enzymes that mediate aspects of the dopamine pathway, along with medication that converts into dopamine.

A ProSavin gene therapy trial relied on a lentivirus as the means to infect cells with pathways that contain the enzymes for making dopamine. Researchers delivered the gene therapy in a single operation on both sides of the brain into the area where dopamine is normally released. They found that using three different doses, delivered in slightly different ways, produced a benefit. However, the benefit was not as effective as DBS and other therapies.

Based on that study, Oxford BioMedica came up with a new gene therapy called OXB-102, which was later bought by Sio Gene Therapies. The study was to have three cohorts of increasing doses, however, the trial was stopped for financial reasons. We cannot draw firm conclusions; however, preliminary research shows the therapy may offer some signs of disease stabilization. Oxford BioMedica now has the license but is not developing the therapy.

Parallel to the above study, U.S.-based Voyager Therapeutics ran a trial using an enzyme associated with making dopamine. Researchers used a similar process — giving different doses to different groups of participants, correctly hypothesizing that giving more gene therapy would induce a bigger response. However, the study was placed on a clinical hold in 2020 by the U.S. Food and Drug Administration when magnetic resonance imaging (MRI) showed unexplained brain abnormalities or changes. That same year, study funding ended to prioritize other research.

• Overall, dopamine gene therapies have yet to be shown to work, but researchers say they continue to hold promise.

On the Horizon: Glucocerebrosidase (GCase) Gene Therapy

A mutated GBA gene (that makes the enzyme glucocerebrosidase) is one of the most common genetic risk factors for Parkinson’s. Up to 10 percent of people with PD have this mutation in one copy of the gene. Researchers believe the GBA mutation can cause enzyme activity to drop, predisposing someone to PD.

A Prevail gene therapy trial currently underway called Propel injects gene therapy into participants with GBA1 Parkinson's. At this stage, the study is evaluating:

• Long-term therapy safety
• Immunosuppression requirements (due to therapy-related inflammation)
• The immune response
• Preliminary effectiveness indicators

Cell Therapies

Every person has about 400,000 to 500,000 dopamine cells. When a person has lost about half of those (200,000 or more) they begin to experience PD movement symptoms. Cell replacement aims to inject new dopamine cells into the brain to replace those that are lost or dying. Such therapy could provide the maximum benefit of dopamine medications with none of the side effects.

Trials have been going on since the late 1980s using human fetal dopamine cells. Around 2007, science developed the capacity to take a human stem cell (a cell that divides indefinitely and can be directed to become any type of cell) and turn it into the type of dopamine cell lost in PD. Allogeneic stem cells are those derived from another human. Autologous stem cells are taken from the person for whom they will be used.

Analysis suggests that younger people with less advanced PD fare better with cell therapy. Tissue preparation prior to implantation, post-graph length of immunosuppression to prevent tissue rejection and long-term follow-up also appear to be important.

Learn More

The Parkinson’s Foundation believes in empowering the Parkinson’s community through education. Learn more about PD and the topics in this article through our below resources, or by calling our free Helpline at 1-800-4PD-INFO (1-800-473-4636) for answers to your Parkinson’s questions.

• Genetics Behind Parkinson's
• PD GENEration: Mapping the Future of Parkinson's Disease
• Join A Study
• Advocate for Research