Medical marijuana, or cannabis, is one of the most popular topics among the Parkinson’s disease (PD) community ― for people with PD, health professionals and researchers, alike. Earlier this year, the Parkinson’s Foundation hosted its first-ever convening on marijuana and Parkinson’s. Among the 46 attendees, of which 17 gave presentations, there was a reoccurring theme: what are the biggest hurdles the PD community faces when it comes to medical marijuana? 

This is the second article in a two-part series. Read part one here.

Adverse Effects

Some of the most common side effects of cannabis-based products include:

• drowsiness and fatigue
• dizziness
• dry mouth
• anxiety
• nausea
• cognitive effects

Specifically, for smoked forms, side effects include cough, increased phlegm and bronchitis. Some rare but important side effects to note include: orthostatic hypotension, paranoia, depression, worsening of coordination of movement and rapid beating of the heart.

Specifically, regarding cognitive function, one review article of several studies found that attention and concentration were impaired in the short term (0-6 hours after use) but largely returned to normal in the longer term (three weeks or longer after use). However, decision making and risk taking were impaired three weeks or more after last cannabis use. Working memory was impaired shortly after use, but did not see any residual or long-term effects. Mixed results were seen as to whether there are long-term effects on impulsivity and verbal fluency after cannabis use.

→ Danny Bega, MD, MSCI, from Northwestern University Feinberg School of Medicine, spoke about this topic at the marijuana convening.

Finding the Right Formula

Physicians and pharmacologists are constantly trying to define the limits of their practice when it comes to cannabis. Not only must researchers find the right formula, they must also find the right delivery method. Cannabis can be delivered in various forms, from liquids to e-liquid (vapor) and inhalers to patches. 

One additional challenge is that cannabis products are not highly regulated, so there can be a lot of variation from product to product and even from batch to batch within a single product. This needs to be regulated more so that people can know what is in the product they are purchasing and trust that it is safe.

→ Bill Arnold, CEO of Cannoid, LLC, spoke about this topic at the marijuana convening.

The Effects of Cannabis and Pain on Men VS Women

Of the 20 common conditions that qualify for medical marijuana, chronic pain has substantial evidence supporting the use of cannabis. People with PD report pain as one of the most common non-motor symptoms, which is not always responsive to pain medications.

PD-related pain is most common among women. Differences between men and women specifically in their susceptibility to intoxication and abuse liability have not been studied. Preclinical evidence suggests that female laboratory animals are more sensitive to cannabinoid (THC) relative to males in terms of treating pain, but they are also more sensitive to the abuse-related effects of these drugs. However, female animals develop tolerance to the pain-relieving effects of THC at a faster rate than males, rendering THC close to ineffective in females.

Ziva D. Cooper, PhD, and her colleagues tested cannabis to see if these findings in animals would translate to humans. Her study found that women who heavily smoke cannabis did not show a pain-relieving response, whereas men did. Regardless of pain response, women reported feeling as intoxicated as men and reported liking the cannabis as much as men.

Future studies investigating the use of cannabis and cannabinoids for PD-related pain are warranted.  These studies should consider differences between men and women, cannabis experience and adverse effects.

→ Ziva D. Cooper, PhD, from the UCLA Cannabis Research Initiative, spoke about this topic at the marijuana convening.

The medical marijuana convening brought together a diverse group of experts from academia, clinics, industry, government and the Parkinson's community to establish a consensus on medical marijuana use in PD. The Parkinson’s Foundation will publish its findings on the convening in summer 2020. 

Learn more about Parkinson’s and marijuana at Parkinson.org/Marijuana.

Medical marijuana, or cannabis, is one of the most popular topics among the Parkinson’s disease (PD) community ― for people with PD, health professionals and researchers, alike. Earlier this year, the Parkinson’s Foundation hosted its first-ever convening on marijuana and Parkinson’s. Among the 46 attendees, of which 17 gave presentations, there was a reoccurring theme: what are the biggest hurdles the PD community faces when it comes to medical marijuana?  

This is the first article in a two-part series. Read part two here.

Treating Parkinson’s Symptoms with Cannabis

There is not enough evidence yet to support that medical marijuana can help manage Parkinson’s symptoms, however there are studies on the topic. Unfortunately, they have mixed results. Generally, the studies have been small and some with no control groups. The effects of medical marijuana are not completely understood, especially in the PD population. The bottom line is that more studies are needed, specifically larger and more rigorously conducted studies.

Based on some observational studies, cannabinoids (the active molecules in marijuana) may potentially benefit some non-motor symptoms of PD including pain, anxiety, sleep problems (insomnia, RBD, RLS), weight loss and nausea. Potential adverse effects include dizziness, blurring of vision, loss of balance, mood and behavioral changes, hallucinations, and impaired cognition and motivation. Better studies are necessary to confirm these benefit and adverse effects for people with PD.

Controlled clinical trials of cannabinoids (where some people receive the drug and some do not) have  reported mixed results for treating motor symptoms and levodopa-induced dyskinesia as well as improving quality of life.

While stories and videos exist showing that marijuana can treat PD symptoms, the challenge is showing that cannabis is better and safer than treatments that are currently available. A recent survey shows that the health community does not have a consensus on using cannabis as a treatment. This reflects lack of data, knowledge and training on the subject.

Future studies about medical marijuana and Parkinson’s should follow the highest standards of clinical trials to focus on:

• Delivery type: do specific strains, soft gels, tinctures (alcohol-based cannabis extract), e-liquid (vapor), topicals, infused food, flower products, inhalers and patches treat symptoms differently and have different side effect profiles?
• Dosage: what is the minimum dosage to guarantee effectiveness, what is the maximum dose tolerated and what dose will have a sustained benefit? Furthermore, how does this differ by strain and formulation?
• Effect on motor vs non-motor symptoms: which symptoms can improve, worsen or stay the same with cannabis use?
• Interaction with PD medications: how does cannabis interact with medications taken for PD symptoms?
• Key component: What components of cannabis/marijuana provide the best response in PD with the least risk of side effects?  What is the optimal CBD (Cannabidiol) to THC ratio?
• PD-specific side effects: are people with PD uniquely susceptible to certain side effects that are not seen in the general population?
• Population: studies that involve participants in difference stages of the disease.

Lastly, there needs to be a widespread physician education on using cannabis as a treatment ― almost all physicians surveyed agreed that medical school curriculums should include education on cannabis.

→ Danny Bega, MD, MSCI, from Northwestern University Feinberg School of Medicine; Joseph Jankovic, MD, from Baylor College of Medicine; and Karl Kieburtz, MD, MPH, from the University of Rochester, spoke about this topic at the marijuana convening.

Potential Drug Interactions

One surprising fact shared at the meeting is that cannabis-based products have the potential to interact with other medications. Given that people with Parkinson’s may be on multiple medications for other conditions, it is important to be aware of these interactions to avoid complications.

Epidiolex® is the first FDA-approved cannabinoid prescription drug. It is an oral solution of cannabidiol most commonly used to treat rare forms of epilepsy. It has been shown to have interactions with many anti-seizure medications, some antibiotics and medications for lowering cholesterol, pain, anxiety, depression and blood pressure. In some cases, Epidiolex can make these medications more or less potent. In other cases, these medications can make Epidiolex more or less potent. Because Epidiolex largely contains cannabidiol, there is the possibility that other cannabis-based products may also interact with medications in a similar way.

Delta-9-tetrahydrocannibinol (THC) is the primary psychoactive component of marijuana (the part that gives a “high”). It can take a long time to take effect and cannot be easily measured for a therapeutic or medicinal dose. THC can also interact with certain medications such as valproic acid (for bipolar disorder, seizures, and migraines) and can result in increased psychoactive effects of marijuana.

Medical marijuana can be taken in an edible form. Care should be taken with this form, as it takes longer to feel an effect and lasts longer (4-8 hours as opposed to 2-3 hours for smoking or vaporizing). Often, because the effects are slow, people increase their dose, eating more, which can be dangerous. Edibles may also have more toxicity than smoked marijuana, because they are broken down by the liver into more toxic chemicals.

→ Jacqueline Bainbridge, PharmD, FCCP, MSCS, from the University of Colorado, spoke about this topic at the marijuana convening.

The medical marijuana convening brought together a diverse group of experts from academia, clinics, industry, government and the Parkinson's community to establish a consensus on medical marijuana use in PD. The Parkinson’s Foundation will publish its findings on the convening in summer 2020. 

Learn more about Parkinson’s and marijuana at Parkinson.org/Marijuana.

One of the most common genetic risk factors for Parkinson’s disease (PD) is having a mutated GBA gene (which makes the enzyme glucocerebrosidase). In fact, 5 to 10 percent of people with PD have that specific GBA mutation in one copy of the gene (mutations in both copies of the gene lead to Gaucher disease). It is more common than other genetic mutations associated with PD such as LRKK2, α-synuclein (SNCA) and PARK2. People with PD who have the GBA mutation tend to experience motor symptom deficits sooner, cognitive decline more rapidly and have particular difficulty with their gait (walking) and postural balance.

When GBA works as it should, it helps code (provide instructions) for making a digestive enzyme that breaks down potentially harmful substances, getting rid of unwanted bacteria and performs various housekeeping duties, including recycling worn out cell components. If both copies of the GBA gene are damaged (mutated), this negatively impacts a cascade of essential processes — which can lead to a dangerous build-up of toxins that harm the spleen, liver, lungs, bone marrow and brain (Gaucher disease). To date, most studies assessing GBA-related PD risk have been performed primarily in European and Asian-derived populations, while very few studies have been done in other populations, such as in the Latino population of South America.

A recently published study, titled, “The distribution and risk effect of GBA variants in a large cohort of PD from Columbia and Peru” (Velez-Pardo et al., 2019) sought to remedy that shortfall and characterize the frequency and distribution of GBA variants (variations in the gene). Specifically, Valez-Pardo et al. (2019) sequenced the entire GBA coding region in 602 participants with PD and 319 controls (people who do not have PD) from Colombia and Peru — all of whom were enrolled in the Latin American Research Consortium on the Genetics of Parkinson's disease. Age at enrollment was comparable for all participants. All study participants were evaluated by a movement disorder specialist at each site and met UK PD Society Brain Bank criteria for PD. The study used a blood test to sequence DNA from each participant.

Results

• A significantly higher proportion of GBA mutation carriers (mutation in one copy of the gene) were seen in people with PD compared to people without Parkinson’s.  
• Those with GBA mutations from Peru and Columbia have a 4- and 6-fold increase in PD risk, respectively.
• The age at onset was significantly earlier in GBA carriers (about 8 years) when compared to people with PD who were non-carriers.
• A novel population-specific GBA mutation called, p.K198E was found only in Colombian participants. This was the first study to identify the p.K198E mutation.
• Frequency of GBA mutations in Colombian participants was more than double most populations, e.g., Peruvian participants and European-derived populations. Note: This was primarily due to the presence of a population-specific mutation, p.K198E.

What Does It Mean?

While the specific biological mechanisms are still unclear, this study found that genetic changes in the GBA gene is linked to a higher risk of developing PD in both Columbians and Peruvians. Further, the novel mutation (p.K198E) the authors identified, found exclusively in the Columbian population, suggests there may be more yet to be discovered mutations in Latin American populations, that could provide unique insights into the disease mechanism.

Moreover, as nearly 10% of the Columbian population carries the GBA mutation — as opposed to about only 4% in other populations — the Columbian PD population may be particularly well suited as a group to study novel therapeutic approaches targeting GBA-related PD.

Learn More

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

• Common Genetic Mutations
• FAQs: Genetics & Parkinson’s
• Episode 7: Genetics as a Guide to Neuroprotection in Parkinson’s Disease

A new study finds vitamin D levels are significantly correlated with falls and some non-motor symptoms in people with Parkinson’s disease (PD). The results of this clinical trial appear in the March 9, 2019 edition of Neurologica.

Vitamin D deficiency is widespread in people with PD. Although epidemiological studies have investigated the relationship between PD progression and vitamin D levels, the results have been mixed. Some studies have reported a higher prevalence of vitamin D deficiency in people with PD compared to those without PD, while others did not find a relationship between vitamin D and PD progression.

Previous studies of vitamin D and PD only focused on one or two aspects of PD and did not include non-motor symptoms, which can seriously limit quality of life. Vitamin D has a vital role in bone metabolism. Lack of vitamin D is correlated with an increased risk of falls and fractures. This can increase hospitalization and even fatal disability rates in people with PD. Studies have also shown that vitamin D levels are associated with cognition and mood in people with PD.

For the new study, researchers led by Jing Chen and Chun-Feng Liu at the Department of Neurology, Second Affiliated Hospital of Soochow University in Suzhou, China, studied 182 participants with PD and 185 people without PD. Researchers measured participants’ vitamin D levels and bone mineral density (BMD) of the lumbar spine and femoral neck (located near the top of the femur bone).

Results

• PD Participants had significantly lower vitamin D levels in their blood compared with people without PD.
• PD participants with lower vitamin D levels had significantly higher frequency of falls and insomnia.
• PD participants with lower vitamin D levels had significantly higher scores for the Pittsburgh Sleep Quality Index (a measure of sleep problems, depression and anxiety).
• Participants with PD had significantly lower mean BMD of the lumbar spine and femoral neck.

What Does It Mean?

This study clearly identified associations between vitamin D levels and some non-motor symptoms in people with PD. The results indicate that vitamin D deficiency may play a role in the development of PD and suggests that vitamin D supplementation may be useful in treating the non-motor symptoms of PD.

The researchers conclude that overall, the findings support further study of vitamin D supplementation for its possible benefits on both the clinical symptoms and quality of life of people with PD.

Learn More

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

• Over the Counter & Complementary Therapies
• Diet & Nutrition
• The Latest in Nutrition and Parkinson’s Disease

Over the next three years the Parkinson’s Foundation will invest more than $50 million to Parkinson’s disease (PD) research and clinical care. At the heart of our research initiatives are scientists and researchers who have received Foundation awards to improve our understanding of Parkinson’s, which will ultimately lead us to a cure.

A key feature of Parkinson’s disease is abnormal protein clumping within nerve cells or neurons. These protein clumps, called aggregates, spread throughout the nervous system as Parkinson’s progresses. How this occurs remains unclear.

Mutations in the GBA1 gene are a strong genetic risk factor for developing Parkinson’s. They are also linked with faster progression of motor and cognitive symptoms.

Marie Ynez Davis, MD, PhD, of VA Puget Sound, received a Clinical Research Award from the Parkinson’s Foundation to investigate a potential new role for the gene GBA1 in speeding the spread of protein aggregates through exosomes. These are small bubble-like structures released by neurons and other cells. They contain proteins and other material that can travel and be received by other neurons and cells.

Dr. Davis’ goal is to find out whether a lack of GBA1 influences the development of Parkinson’s by increasing the number of exosomes and the proteins inside them that can be delivered to other neurons. This could promote clumping in the receiving neurons throughout the nervous system.

To achieve this goal, she will study human neurons from people with GBA1 mutations and Parkinson’s. She will examine the development and structure of exosomes. She will also look at their ability to promote protein aggregation.

Our hope is that results from this work will improve our understanding of how Parkinson’s occurs. It may also reveal new targets for therapies that could halt or slow progression of the disease.

Parkinson's Foundation Clinical Research Awards help facilitate the development of clinician scientists, ensuring that promising early career scientists stay in the PD field to help us solve, treat and end this disease. 

What's Next: Reporting Our Findings
Parkinson’s Foundation research awards fund Parkinson’s studies than can span up to three years. Scientists submit yearly progress reports to the Parkinson’s Foundation, and we report findings once the studies have concluded. Stay up to date with our latest research findings at Parkinson.org/Blog.

While the leaves may be changing, your favorite podcast isn’t going anywhere! Cozy up, sit back and get ready to learn from our Parkinson’s disease (PD) experts with our top Substantial Matters: Life and Science of Parkinson’s podcast episodes:

1. Stall the Fall
   People with Parkinson’s are two times as likely to fall as other people their age. While healthcare professionals recognize the extent of the problem, there is still a lot to learn about why they happen and what can be done to prevent them.

Listen Now

2. Depression in Parkinson’s 
   With depression as a common PD symptom, people with Parkinson’s should be conscious of their increased susceptibility to seasonal depression. Learn about the symptoms that accompany depression and how they may overlap with PD itself.  

Listen Now

3. The Launch of PD GENEration
   Fall means school is in session. Learn about our latest study, PD GENEration: Mapping the Future of Parkinson’s Disease, and how it aims to help uncover key mechanisms responsible for PD and its progression.

Listen Now

4. Seeking a Second Opinion After a Parkinson’s Diagnosis
   People are being newly diagnosed with Parkinson’s year-round. Learn more about seeking a second opinion from a movement disorders specialist. It may help to confirm the diagnosis and address any lingering unanswered questions.

Listen Now

5. Addressing Sleep Discomfort with Parkinson’s
   The seasonal time change can lead to trouble sleeping for everyone, but people with PD experience sleep problems as a symptom. Changes in the brain can affect mood, thinking and the sleep-wake cycle. Find out how to address sleep discomfort.

Listen Now

6. Palliative Care as Supportive Care in PD
   A change in temperature can bring muscle stiffness. As people with PD understand the benefits of palliative care, they are adding it to their regimen. Palliation means to ease the burden of the symptoms of a disease.

Listen Now

7. Dance Therapy for PD
   A change of season can be the perfect time to try something new. Besides medication, people with Parkinson’s can benefit from many other forms of therapy, including physical, occupational, speech, music, art therapies, along with dance/movement therapy (DMT).

Listen Now

If you liked what you heard, subscribe, rate and review the series on Apple podcasts or wherever you get your podcasts.

If you have any questions about the topics listed or want to leave feedback on this podcast or any other subject, you can do so here.

Non-movement Parkinson’s disease (PD) symptoms can impact mental health, relationships and quality of life. The Parkinson’s Foundation has conducted two recent studies dedicated to learning more about treating non-movement symptoms within its Center of Excellence Network.

Centers of Excellence are medical centers with a specialized team who are up to date on the latest Parkinson’s medications, therapists and research to provide the best care to a combined 185,500 people with Parkinson’s.

This year, the Parkinson’s Foundation will share their research findings at two international conferences: at the International Congress of Parkinson’s Disease and Movement Disorders in Nice, France, and at the World Parkinson Congress (WPC), which took place in June at Kyoto, Japan.

Both conferences gather thousands of neurologists, researchers and health professionals in the Parkinson’s community.

Multidisciplinary Care Models for Parkinson’s Disease: The Parkinson’s Foundation Centers of Excellence Experience

People living with Parkinson's benefit most from a comprehensive, team-based healthcare approach, where different specialists treat motor and non-motor symptoms as the disease progresses. Every Center of Excellence works with a multidisciplinary team in one of three different care models:

1. Team members are all in the same institution.
2. Team members are within different, but affiliated institutions.
3. Team members are in separate institutions, mainly community based.

The Parkinson’s Foundation studied usage of complementary health therapies across the three models and examined relationship between therapy usage and clinical outcomes. The study used Parkinson’s Outcomes Project (the largest ongoing Parkinson’s study) data to analyze 10,058 patients from 22 designated centers. The study showed that:

• Therapy referrals varies across different disciplines among Centers of Excellence, with physical therapy being the most common referral.
• Psychosocial and mental health therapies may be underutilized ― in terms of physician’s referrals and patients seeing a mental health professional.  
• There were significant differences in clinical outcomes across care models.

These findings show the need to expand our understanding of how different care models and therapies (such as occupational, physical and psychological) affects care and outcomes for people with PD.

→ This study was shared at the 2019 World Parkinson Congress in Kyoto, Japan. Authors: Clarissa Martinez-Rubio, PhD, Jennifer G. Goldman, MD, MS, Samuel S. Wu, PhD, Hanzhi Gao, Fernando Cubillos, MD, Nadia Romero and Veronica L. Todaro, MPH.

Relationships of Gender, Care Models and Neuropsychiatric Symptoms In Parkinson’s Disease

In this study, the Parkinson’s Foundation compared complementary health therapies across the three care models mentioned above in relation to the difference between men and women living with Parkinson’s, their outcomes, management of the neuropsychiatric symptoms ― specifically depression and psychosis.

Using data from the Parkinson’s Outcomes Project, we studied 10,058 people with PD seeking treatment at 22 Parkinson’s Foundation centers who experienced depression or psychosis, referred to a psychologist or psychiatrist and receiving antipsychotic or antidepressant medication. The study showed that:

• Depression and psychosis are experienced and treated differently depending on gender.
• Psychosocial and mental health therapies may be underutilized ― in terms of physician’s referrals and patients seeing a mental health professional.  
• Significantly more women than men were identified with depression, self-reported limitation of activity due to depression and received antidepressant medication.
• People with Parkinson’s who sought care at a center with an external allied healthcare team were significantly more likely to be hospitalized due to mental health, gastrointestinal issues and DBS-related symptoms.

These findings show the need to expand our understanding of how different care models and usage of complementary therapies affects care and outcomes for people with PD, as well as, the need to expand our understanding on how gender affects these factors

→ This study was shared at the 2019 International Congress of Parkinson’s Disease and Movement Disorders in Nice, France. Authors: Jennifer G. Goldman, MD, MS, Clarissa Martinez-Rubio, PhD, Samuel S. Wu, PhD, Hanzhi Gao, and Veronica L. Todaro, MPH.

Learn more about the Parkinson’s Outcomes Project at Parkinson.org/Research.

About 89 percent of people with Parkinson’s disease (PD) experience speech and voice disorders, including soft, monotone, breathy and hoarse voice and uncertain articulation. Speech disorders can progressively diminish quality of life for a person with PD. The earlier a person receives a baseline speech evaluation and speech therapy, the more likely he or she will be able to maintain communication skills as the disease progresses. Communication is a key element in quality of life and positive self-concept and confidence for people with PD.

Speech and swallowing issues in Parkinson’s can occur for various reasons. The top three issues include:

1. Directly related to the disordered motor system that accompanies PD, including rigidity, slowness of movement and tremor.
2. Change in sensory processing that is related to speech. It is believed that people with PD may not be aware that their speech is getting softer and more difficult to understand.
3. Another cause of this condition is that people with PD may have a problem with “cueing” themselves to produce speech with adequate loudness.

Tell your doctor If you are experiencing any changes in your speech or voice. Ask for a referral and a prescription for a speech evaluation a treatment. If you have not noticed changes in your speech, but a spouse, care partner or friend has pay attention to their comments. The sooner you get a speech evaluation and start speech therapy, the better.

Take Our Quiz

Many people with Parkinson’s have these statements to describe their voices and the effects of their voices on their lives.

Choose the response that indicates how frequently you have the same experience (0 = never, 1 = almost never, 2 = sometimes, 3 = almost always, 4 = always).

To find your score, add up your answers. A score of 10 or higher indicates you might have a speech or voice problem that is affecting your quality of life and you should ask for a referral to a speech pathologist.

The quiz is no longer available.

What next?

The Parkinson’s Foundation Helpline can help you find a nearby speech pathologist who has experience in Parkinson’s. Call our Helpline at 1-800-4PD-INFO (1-800-473-4636).  

Looking for ways to improve your speech and communication? Check out this blog article for ways you can improve your speech starting now. 

For more information about Speech Therapy and Parkinson’s check out our Speech Therapy Fact Sheet and other resources at Parkinson.org.

Parkinson’s disease (PD) is neurodegenerative disorder characterized, in part, by the clumping of the protein alpha-synuclein. These clumping proteins are called Lewy Bodies that can be found in an area of the brain stem where dopamine cells die. However, we do not know exactly how the two are connected. Researchers believe that better understanding this connection would help us develop optimal targeted therapies to treat PD. 

A study published in Nature, “Alpha-synuclein is a DNA binding protein that modulates DNA repair with implications for Lewy body disorders” (Schaser et al., 2019), wondered if healthy alpha-synuclein help repair DNA damage caused by double-strand breaks (DSBs). DSBs can be the result of many things, such as environmental exposure to irradiation and other chemical agents. However, DNA damage is also a normal result of cells undergoing constant wear-and-tear. In fact, DNA damage happens in human cells thousands of times per day. Fortunately, cells repair damaged DNA on their own.

However, what if the unhealthy alpha-synuclein (which becomes Lewy Bodies) causes the loss of DSB repair, leading to healthy cells dying? While this study was not PD-specific, what if it were dopamine-producing cells that were not getting repaired and dying? The researchers conducted a series of sophisticated tests in both living mouse brains and human cells to see if this chain of events was taking place.

First, using a powerful microscope (or imaging techniques) the researchers confirmed that healthy alpha-synuclein appear exactly where the DSBs are located. However, the test did not show the cause, so further experiments were required.

Researchers then measured the amount of DSBs in healthy human cells and human cells where alpha-synuclein was completely removed (known as knock-out cells). To cause DNA breaks, they exposed the cells to a chemotherapy drug, called bleomycin. The researchers found that the cells without alpha-synuclein (knock-out cells) had higher levels of DSBs compared to healthy cells, suggesting that alpha-synuclein plays a role in repairing DSBs. They also found that the healthy human cells repaired DSBs more rapidly compared to the knock-out cells, again supporting the role of alpha-synuclein in aiding DNA repair.

Next, researchers used a strong laser, which they knew would damage the DNA and cause DSBs, to see if healthy alpha-synuclein are recruited there to help seal the breaks. They tested this in two groups of live mice and live human cells: 1. healthy and 2. Group with the disease that carry the abnormal form of alpha-synuclein. Lastly, they tried adding healthy human alpha-synuclein back into the mice without alpha-synuclein to see if it might restore the normal DNA damage response.

Results

• In both human cells in a dish (in vitro) and living mouse brains (in vivo) alpha-synuclein was present in the exact same location as the DNA repair proteins, suggesting alpha-synuclein binds directly to DSBs, and helps repair those breaks.
• In both healthy human cells and living mouse brains, the laser-induced DSBs, triggered alpha-synuclein to move to the site of DNA damage.
• In diseased human cells and mice carrying the abnormal form of alpha-synuclein, the laser-induced DSBs, impaired alpha-synuclein from moving to the site of DNA damage.
• Removing alpha-synuclein in human cells lead to increased DSB levels after receiving chemotherapy drug (bleomycin) treatment, and a reduction in the ability to repair these DSBs, compared to healthy human cells.
• Removing alpha-synuclein in mice (the knock-out mice) also resulted in increased DSBs, following bleomycin treatment.
• Giving healthy human alpha-synuclein to the alpha-synuclein knock-out mice, restored the mice cells’ DNA damage response to normal levels.

What Does This Mean?

This study suggests that the abnormal clumping of alpha-synuclein cells into the form of Lewy Bodies diminishes the available healthy alpha-synuclein to do its job of assisting in DNA damage repair (DSBs). This lack of repair triggers the cell death process, because the cell is damaged to the point where it can no longer function normally.

Of note, while this study was not designed only for Parkinson’s, these finding may offer insights as to how abnormal alpha-synuclein clumping leading to Lewy Bodies may result in the increase of cell death of dopamine-producing cells. These findings could inform the development of new PD treatments that target alpha-synuclein-mediated DNA repair mechanisms.

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

Over the next three years the Parkinson’s Foundation will invest more than $50 million to Parkinson’s disease (PD) research and clinical care. At the heart of our research initiatives are scientists and researchers who have received Foundation awards to improve our understanding of Parkinson’s, which will ultimately lead us to a cure.

The dementia that many people with Parkinson’s disease develop greatly affects both those who experience it as well as their families. Parkinson’s-related dementia is associated with significant increases in illness and death compared with people who have Parkinson’s without dementia. There are currently no tests to determine which people with Parkinson’s will develop dementia and/or how quickly they will do so.

About 80% of people with Parkinson’s develop dementia by about 15 years after their PD symptoms appear. However, there is a wide variation. In some people, dementia begins as early as a few years after PD symptoms start. Other people have near-normal cognition after more than 15 to 20 years of PD motor symptoms. This difference may be related to different strains of the protein alpha-synuclein (α-synuclein), which is central to Parkinson’s.

Liana Rosenthal, MD, PhD, at Johns Hopkins University School of Medicine, received a Parkinson’s Foundation Clinical Research Award to study markers of dementia in people with PD. Her goal is to determine whether a specific, less toxic strain of α-synuclein is associated with slower progression of dementia.

To accomplish this, she will study α-synuclein from the fluid in the brain and spinal cord from people with Parkinson’s with and without dementia. Identifying progression markers for PD-related dementia, might allow us to improve the function and health of people with Parkinson’s.

Parkinson's Foundation Clinical Research Awards help facilitate the development of clinician scientists, ensuring that promising early career scientists stay in the PD field to help us solve, treat and end this disease. 

What's Next: Reporting Our Findings

Parkinson’s Foundation research awards fund Parkinson’s studies than can span up to three years. Scientists submit yearly progress reports to the Parkinson’s Foundation, and we report findings once the studies have concluded. Stay up to date with our latest research findings at Parkinson.org/Blog.