The Parkinson’s Foundation makes research more efficient and effective by involving those living with Parkinson’s disease (PD) in the research process. People  living with PD are experts because they know this disease, its symptoms and how it impacts their lives. The Parkinson’s Foundation Research Advocacy Program (formerly referred to as Patient Advocates in Research) trains research advocates ― people with Parkinson’s and care partners ― to provide their expertise to researchers in academia, government and pharmaceutical companies. Historically, there has not been a universal process in place to help researchers engage research advocates in their work. The Parkinson’s Foundation is changing that.

In May 2020, the Parkinson’s Foundation published an article in the scientific journal Health Expectations outlining a patient engagement framework developed from the Foundation’s 12 years of experience working with research advocates. The framework is designed to help researchers integrate and measure patient engagement in their work, ultimately leading to better studies.

“Over the last decade the Parkinson’s Foundation has learned that there is critical information pharmaceutical companies and academia are missing by not involving people living with Parkinson’s in the research process,” said Megan Feeney, author and Parkinson’s Foundation Senior Manager of Community Engagement. “There are also many researchers open to making patient engagement a priority, but we need evidence to promote this practice.”

This framework provides a clear outline for researchers to follow. “The goal of this framework is to make patient engagement a common practice in the research process for all health conditions, whether a researcher has experience working with patients or not,” Megan said. “This patient engagement framework can be customized by any researcher for any study.”

Patient Engagement Leads to Smarter Research

Why is patient engagement important? Without patient input, research may target the wrong outcomes or design trials without consideration of the preferences of people living with Parkinson’s. In one clinical trial, people with Parkinson’s were excited to help test a new PD medication. However, the clinical trial requirements were burdensome. Due to poor recruitment and retention, the trial could not continue. Had the researchers designed a clinical trial allowing for patient engagement, it could have been more patient friendly, while enrolling and retaining study participants. Read the article for more case studies.

“When you design a clinical study with input from people living with Parkinson’s, each part of the study can be tailored for the community you are trying to help without impacting the quality of the science, making  research  faster and better,” Megan said. The patient engagement framework is now available for all organizations to utilize and tailor to their needs to expedite research and make it relevant to their community.

Parkinson’s and Beyond

Not every organization has a patient engagement process in place, like the Parkinson’s Foundation. Parkinson’s is a complex disease with multiple symptoms (non-movement and movement) that can make the patient engagement process difficult to navigate without the proper planning and resources. The Foundation works to mediate patient engagement so that both people living with Parkinson’s and researchers can contribute and have a positive experience.

“We work with researchers and other patient advocacy organizations all over the world to overcome the challenges that people might experiences when engaging with patients for the first time,” said Karlin Schroeder, co-author and Parkinson’s Foundation Senior Director of Community Engagement. “The ultimate goal is to create an environment for success that helps the most people possible.”

The Parkinson’s Foundation will continue to use its patient engagement framework, helping people with Parkinson’s become empowered to fight this disease through active involvement. “We hope this framework can become a blueprint, reaching beyond Parkinson’s so other patient advocacy groups can utilize this model for other life-impacting diseases and increase patient engagement for the greater good,” Karlin said.

If you are interested in becoming a research advocate or working with research advocates, please email Karlin Schroeder at KSchroeder@Parkinson.org.

Read the full article online “Utilizing Patient Advocates in Parkinson’s Disease: A Proposed Framework for Patient Engagement and the Modern Metrics that Can Determine Its Success in Health Expectations” in Health Expectations.

Impulse control behaviors (ICBs) affect between 14% and 40% of people with Parkinson’s disease (PD). Examples of ICB’s include compulsive gambling or shopping, hoarding and hyper sexuality. ICBs become impulse control disorders (ICD) when they impair one’s ability to function at work, home and navigate day-to-day life. Only 2% of people have ICBs in the general population.

Why the dramatic disparity? It has to do with the gold standard medication for PD: Dopamine replacement therapy, such as L-dopa, as well as dopamine agonists, such as Requip (ropinirole), Mirapex (pramipexole) and Neupro (rotigotine), are all strongly linked to experiencing ICBs. This is because dopamine, in addition to relaying messages that plan and control body movement, also plays a primary role in the reward pathway in our brains ― in other words, it makes us feel good, even elated.

Since ICBs are commonly experienced as highly pleasurable ― and even anxiety-relieving ― people with ICBs may go to great lengths to hide their compulsions from friends, family and their healthcare professionals. Unfortunately, all too often, this concealment results in detrimental personal and financial consequences. There is a need to better understand the Parkinson’s-ICB connection.

A large, three-year, prospective, multi-center study published in Neurology titled, “Impulse control disorders in Parkinson disease and RBD: A longitudinal study of severity” (Baig et al., 2019) sought to address four key questions:

1. What is the distribution and severity of PD-ICBs?
2. How does this vary over time?
3. How common are Parkinson’s ICBs?
4. Which clinical factors are associated with PD-ICBs?

In this study, otherwise healthy people with ICBs were compared with those who had PD and a REM sleep behavior disorder (RBD). Why was REM chosen? Previous studies have suggested that the presence of RBDs may infer a higher risk of developing PD-ICD. However, it is not known whether RBD itself, or whether a particular RBD-PD subtype, increases that risk.

There were 932 PD participants in the study. Due to factors such as withdrawal and deaths, 531 completed the study. Those with RBD (and the control arm) were clinically screened for ICBs using the Questionnaire for Impulsivity in Parkinson’s Disease. Those who were ICB-positive were then invited to participate in a semi-structured interview, that was repeated every 18 months. Clinical assessments were performed with a variety of tools to assess a broad range of motor and non-motor symptoms at each visit. Severity of the ICB was assessed with the Parkinson’s Impulse Control Scale, and ICB prevalence and associations were mathematically calculated.

Results

• Impulse control behaviors were common in the early stages of PD (19.1% prevalence).
• There were no increased risks for having ICBs associated age, sex, cognition, sleep disorders or marital status.
• The incidence of depression was higher among participants with PD with ICD than those without.
• There was significant variation in the severity (both the impact and intensity) of PD-ICB – fluctuating within a relatively short period of time.
• Internal factors (mood and coping mechanisms) impacted the severity of PD-related Impulse control behaviors.
• External factors (major life events and social support) also impacted the severity of the PD-ICBs.

What Does This Mean?

This study found that ICBs are common in the early stages of PD, with a larger proportion of this population having symptoms of ICD, but not enough for the behavior to be designated a disorder. While scientists have known for over a decade that dopamine-related drugs could be linked to ICDs in some people with PD, it wasn’t until 2004 that people living with Parkinson’s began to learn that ICDs could be a rare side effect of dopamine agonists.

Thus, dopamine dosage changes may need to be considered, when ICB or ICD behaviors appear to be present. Lastly, people with PD, and their care partners, need to be aware that internal (mood and coping mechanisms) and external factors (major life events and social support) were found to be contributing causes for progressing from an impulse control behavior problem to a disorder.

Learn More

Learn more about Parkinson’s and impulse control issues in the following Parkinson’s Foundation resources or by calling our free Helpline at 1-800-4PD-INFO (473-4636):

• Fact Sheet: Impulse Control
• Why Do I Keep Doing This? Impulsivity

For more insights on this topic, listen to our podcast episode “Clinical Issues Behind Impulse Control Disorders.”

PD GENEration: Mapping the Future of Parkinson’s Disease, which launched last year, is one step closer to understanding the complex connection between Parkinson’s disease (PD) and genetics.

The goal of PD GENEration is to leverage genetics as a powerful tool to help us uncover what is responsible for slowing or stopping the progression of Parkinson’s, which will ultimately improve care and speed the development of new treatments. Study results will advance how we design clinical trials, for instance, testing a new medication based on what type of PD gene a person carries.

As the first national Parkinson’s study to offer bilingual genetic testing in a clinical setting with counseling, the Parkinson’s Foundation flagship study has unearthed exciting preliminary findings.

Higher Detection Rate

Of the 291 people who have been tested as part of the study, 51 tested positive with a genetic mutation that is linked to PD. This amounts to 17% of all PD GENEration participants.

This percentage is higher than the current reported estimates of one to 10% of people with PD who have a genetic connection to the disease — a range that is not representative of the entire PD population since not everyone with Parkinson’s has been genetically tested. PD GENEration researchers theorize that as more people with PD get genetically tested, the rate of detection will most likely rise.

Discovering Rare Mutations

Genetic test results have led researchers to identify extremely rare genetic mutations linked to PD. Some study participants carry multiple mutations, meaning one person can carry two or three different genetic mutations associated with PD.

These multiple genetic mutation carriers have not been extensively studied — thus, we do not know how living with multiple genetic mutations affects PD symptoms or progression. This finding will significantly contribute to the biological understanding of the disease, helping us assess the impact of each mutation and which ones are more influential towards causing the disease, which will lead to better treatments.

Creating an International PD Panel

PD GENEration is working to finalize the development of a global leadership council on genetics and  PD. The international expert PD panel convenes leading clinicians, molecular biologists and geneticists who will develop global consensus to decide which genes and mutations are important for PD and will accelerate research efforts towards better PD treatments.

“This panel welcomes anyone and everyone who is significant in genetics and PD,” said James Beck, PhD, Parkinson’s Foundation Chief Scientific Officer. “It will be a platform for experts from around the world to assess PD GENEration data in real time — data that has already led us to new findings.”

A Community Dedicated to Research

As evidence that the study’s outreach to the PD community goes far beyond the Foundation’s immediate network, 33% of the PD GENEration participants came from outside of the Parkinson’s Foundation Centers of Excellence network. Participants traveled from 21 states to six pilot sites.

“This community is determined and resilient to do what it takes to contribute to Parkinson’s research, a great indication that we will be able to successfully complete our goal of enrolling 15,000 participants who want to know if they have a genetic link to this disease,” Dr. Beck said.

The Next Phase

The PD GENEration study will expand to more testing sites. In response to the current climate, PD GENEration leaders are designing a telemedicine-based approach, where participants can submit their test using an at-home kit and complete virtual, bilingual genetic counseling.

PD GENEration recently partnered with Biogen to accelerate the study. Looking ahead, once PD GENEration is complete, the partnership will help drug development companies, like Biogen and others, recruit for clinical trials faster. This will help speed up the development of better PD medications and recruitment for PD clinical trials.

Learn more about PD GENEration and sign up for email updates at Parkinson.org/PDGENEration.

The gut-brain relationship is real. Stomach or intestinal distress can lead to anxiety or depression. However, those gut-brain connections go much further: evidence from recent studies strongly suggest a link between the gut (the gastrointestinal system) and Parkinson’s disease (PD).

In the PD research field, the Braak Hypothesis states that the earliest signs of Parkinson's are found in the enteric nervous system (known as the brain in the gut). This theory is supported by evidence that in PD, non-motor symptoms, such as constipation, may appear before motor symptoms. Braak hypothesized that abnormal alpha-synuclein can spread from the gut via the vagus nerve to the midbrain, where it selectively kills dopamine neurons.

Published in Neuron, a 2019 study titled, “Transneuronal Propagation of Pathologic alpha-Synuclein from the Gut to the Brain Models Parkinson's Disease" (Kim et al., 2019) a group of scientists tested Braak’s hypotheses, mimicking the spread of abnormal alpha-synuclein observed in PD, scientists injected both normal mice and knock-out mice (mice with no alpha-synuclein) with misfolded alpha-synuclein directly into the stomach opening and part of the small intestine ― which are packed with vagus nerve branches.

To monitor the injected abnormal alpha-synuclein, scientists used a stain to observe the progression, if any, from the gut to the brain over several months. They also tested severing the vagus nerve in the mice, to see whether it might prevent the spread of the abnormal alpha-synuclein to the brain. Additionally, throughout the study, several tests were conducted on the mice to measure motor and non-motor symptoms.

Results
In normal mice:

• Injecting abnormal alpha-synuclein into the gut did get taken by the vagus nerve and successfully traveled into the brain, causing the normal alpha-synuclein to transform into abnormal, misfolded alpha-synuclein.
• This transformation process traveled from cell-to-cell, forming more Lewy body clumps. Remember, misfolded alpha-synuclein is the main component of Lewy bodies.   
• Injecting abnormal alpha-synuclein into their gut resulted in significant dopamine loss.

In the mice with no alpha-synuclein:

• Injecting abnormal alpha-synuclein into their gut successfully made it into the brain, but nothing happened. Since there was no normal alpha-synuclein, it was not able to start the clumping.

Motor and Non-Motor Findings

Seven months after injecting abnormal alpha-synuclein into the gut of normal mice:

• There was a significant loss of dopamine in the brain.
• There were non-motor cognitive impairments, including memory and social deficits, anxiety, depression and olfactory and gastrointestinal dysfunction.
• Motor deficits included a loss of grip strength and agility.
• Those mice that had their vagus nerve severed prevented the loss of grip strength and agility shortfalls.

What Does This Mean?
The major findings of this study support that abnormal alpha-synuclein is capable of spreading from the gastrointestinal tract (the gut) through the vagus nerve into the brain, leading to a loss of dopamine.

Further, the Kim et al. (2019) study also revealed that the misfolded alpha-synuclein in the brain causes the normal alpha-synuclein to misfold; and those misfolds form into clumps, resulting in Lewy bodies, which in turn, result in Parkinsonian symptoms. In terms of potential therapeutic applications, if this gut-brain PD connection via the vagus nerve works the same way in people, it may be possible to interfere with this trafficking to prevent PD symptom progression before it reaches the brain.

Learn More
The Parkinson’s Foundation believes in empowering the Parkinson’s community through education. Learn more about the Parkinson’s and LID in the below Parkinson’s Foundation resources or by calling our free Helpline at 1-800-4PD-INFO (473-4636).

• Protein May Hold Clues to Development of Parkinson’s