Freezing of gait is a common Parkinson’s disease (PD) symptom where a person experiences the temporary, involuntary inability to move. This can make simple activities, like walking across a room, incredibly challenging and dangerous due to the risk of falls. Unfortunately, common Parkinson’s medications often don’t alleviate these freezing episodes. This has led researchers like Amitabh Bhattacharya, PhD, from the University Health Network (UHN) in Canada, to explore new treatments. 

Dr. Bhattacharya is a recipient of a 2024 Parkinson’s Foundation Postdoctoral Fellowship, and will use this support to study how TUS can be utilized to help people with PD create personalized non-invasive treatments that targets freezing of gait. 

“We will apply focused ultrasound waves to a specific part of the brain known as the pedunculopontine nucleus (PPN), a key region that helps control movement,” he said. “By precisely stimulating the PPN, we hope to make walking easier for people with Parkinson’s.” 

Participants, recruited with help from the Toronto Western Hospital Movement Disorders Clinic, a Parkinson’s Foundation Center of Excellence, will first undergo a high-resolution brain scan to create a detailed map of their brain, focusing on the PPN. This personalized brain map will guide the ultrasound device to ensure that the sound waves are precisely directed to the right spot.  

Each participant will receive three personalized TUS treatments, using different stimulation protocols to determine the most effective approach. To evaluate how well each protocol works, participants will be assessed before and after each session using tests that measure their walking ability, mental function, and brain activity. 

Finally, Dr. Bhattacharya will have enough scientific evidence to determine the ability of TUS in improving freezing of gait, as well as how to keep improving the technique to make it even safer and more effective. 

Dr. Bhattacharya is confident in this treatment’s potential to improve the lives of those experiencing PD-associated freezing of gait. “Targeting the PPN through non-invasive means such as TUS holds immense promise,” he said. “The ability of PPN-TUS to modulate these essential neural circuits could help restore a degree of normal motor function, thereby mitigating symptoms such as freezing of gait in PD.”  

The goal of this study is to explore TUS as a practical and effective treatment for freezing of gait in Parkinson’s Disease. TUS is a non-invasive approach that could offer a quicker, more accessible, and cost-effective option for patients. By avoiding the complexities and recovery time associated with surgical procedures like deep-brain stimulation (DBS), TUS has the potential to enhance mobility and improve quality of life. The accessibility of this new potential treatment is top-of-mind for Dr. Bhattacharya.  

“PPN-TUS offers a non-invasive, cost-effective alternative with fewer potential complications compared to PPN-DBS,” he said. “This study could transform the way we help Parkinson's patients regain their mobility. If successful, this non-invasive method may eventually become a standard treatment, offering improved quality of life for individuals with Parkinson’s disease.” 

Meet more Parkinson’s researchers! Explore our My PD Stories featuring PD researchers.

Thanks to our wonderful donors and community, we are excited to announce that our Reach Further fundraising campaign exceeded its goal early. In just three years, we raised $38.4 million to accelerate progress in Parkinson’s disease (PD) research, improve care and increase access to quality-of-life programs.

“Exceeding our campaign goal is a huge milestone, and we are so grateful to every person who made this campaign a priority,” said John L. Lehr, president and CEO of the Parkinson’s Foundation. “These funds allow us to accelerate our mission and create lasting impact in the lives of people with Parkinson’s.”

Launched in 2021, the Reach Further campaign helped fund PD programs and provide resources to local communities across the nation, providing support to people with Parkinson’s and their loved ones.

Here are four of the ways your support of the Reach Further campaign helped us impact people with Parkinson’s:

1. Recruited more than 15,000 participants for PD GENEration: Mapping the Future of Parkinson’s disease, our landmark genetics initiative. We also expanded access to the study to Black and African American communities, as well as Spanish-speaking communities in the U.S. and throughout the Western Hemisphere.

Thanks to this expansion, more people with Parkinson’s know if they have a genetic form of PD and have received genetic counseling to understand their results. So far, the study has identified that 12.7% of participants have a genetic form of PD.

Increasing the number of people participating in PD GENEration, and ensuring we are testing a diverse population, an accelerate relevant clinical trials, bringing us closer to a better understanding of PD and identifying potential new treatments.

Enroll Now

2. Launched Parkinson’s Virtual Biotech in partnership with Parkinson’s UK to build a pipeline of new drugs exclusively aimed to target Parkinson’s.

Taking a new drug from an idea to becoming an available medication can take years and upwards of one billion dollars. The Parkinson’s Virtual Biotech works to accelerate that timeline by building a pipeline of new drugs exclusively for Parkinson’s.

The Parkinson’s Virtual Biotech is directly investing in medications that either address symptoms or aim to slow, stop or prevent the disease altogether.

Discover the drugs in development right now

3. Expanded our Global Care Network, adding 18 new Center designations to provide better, more attainable care.

Finding the right care team can improve the health and quality of life of a person with Parkinson’s. Our Global Care Network aims to make high-quality care accessible to more people with Parkinson’s, while also providing health professionals the chance to advance their skills and share their knowledge.

Through expanding our Global Care Network, we are taking one step closer to our goal of ensuring all people with PD have access to the equitable and quality care they need, when and where they need it.

Find expert care near you

4. Awarded $4 million in community grants across the U.S., addressing critical needs such as exercise, mental health and care partner support.

From dance classes to Rock Steady Boxing workout classes, local PD programs empower people with Parkinson’s and help them find community support. Through our community grants, we are proud to support the dedicated professionals and volunteers offering vital programs and resources to people with Parkinson’s around the country. These programs foster local Parkinson’s communities and help people live better with PD.

Find a program in your community

THANK YOU for helping us make life better for people with Parkinson’s through your support of the Reach Further campaign. These impact-driven achievements could not have happened without your support. Your generosity continues to elevate our research, care and education programs to new heights.

Discover new ways you can help the Parkinson’s community. Learn more about the Parkinson’s Foundation at Parkinson.org or 1.800.4PD.INFO (1-800-473-4636).

Guanylyl cyclase C (GUCY2C) is protective against dopamine neuron degeneration, a hallmark of Parkinson’s, by helping the cell’s powerhouse.

A new study is the first to identify a brain receptor called GUCY2C as a potential way to fight dopamine loss.

Parkinson’s disease (PD) is caused by the death of neurons that produce dopamine — a feel-good chemical related to movement, mood and more — in the brain. Dopamine neurons are involved in movement and the loss of these neurons disrupts the brain's ability to regulate movement, leading to hallmark PD symptoms, such as tremors, rigidity and slowness.

One of the reasons that dopamine neurons die is due to dysfunction of mitochondria, the small oxygen-consuming and energy-producing powerhouses inside cells. Recent research has found a receptor on the surfaces of those Parkinson’s-associated dopamine neurons that may provide therapeutic ways to protect the mitochondria and prevent the progression of the disease.

The receptor, called guanylyl cyclase C (GUCY2C), was first discovered on the surfaces of cells in the intestine, but was recently found in a region of the brain called the substantia nigra pars compacta (SNpc). This area of the brain is affected in PD.

A new study led by Scott Waldman, MD, PhD, and funded by the Parkinson’s Foundation 2023 Impact Award, gives a clearer picture of how GUCY2C signaling can provide protection against mitochondrial dysregulation and dopamine neuron degeneration that leads to PD. According to the study, in people with Parkinson’s, dopamine neurons make extra GUCY2C receptors.

About the Study & Results

Dr. Waldman and his team studied mice with and without the GUCY2C receptor. They found that loss of GUCY2C led to mitochondrial dysfunction, oxidative stress and cell death within the part of the brain impacted by PD, suggesting a protective nature of GUCY2C.

When the researchers gave the two groups of mice a toxin that induces PD symptoms by targeting mitochondria in dopamine neurons, only mice that did not have GUCY2C receptors had higher rates of dopamine neuron death. In contrast, mice with GUCY2C increased their production of the protein upon treatment with the toxin, further indicating a protective role.

The researchers also found that cyclic GMP (cGMP), a byproduct of GUCY2C activation, protected dopamine neurons from oxidative stress. In neurons grown in a petri dish, adding a molecule that increases cGMP protected dopamine neurons from oxidative stress and mitochondrial dysfunction when they added the PD-inducing toxin.

These results indicate that in Parkinson’s disease, the increase in GUCY2C might be the body's attempt to protect dopamine neurons from damage. It may be possible to develop a molecule that targets GUCY2C or use existing drugs that increase cGMP to protect dopamine neurons from damage.

Highlights

• Loss of the receptor GUCY2C led to dopamine neuron degeneration in mice — in other words, not having the GUCY2C receptor led to neuronal dysfunction in brain regions implicated in PD.
• A molecule that increases cGMP (a byproduct of GUCY2C activation) protected neurons grown in a petri dish from mitochondrial dysfunction and cell death when the researchers added a toxin that induces neurodegeneration.
• Because GUCY2C is increased in people with Parkinson’s, the study results suggest that the increase in GUCY2C may be the body's attempt to protect dopamine neurons from damage.

What does this mean?

This study is the first to identify the receptor GUCY2C as a possible defense mechanism against dopamine loss. This research marks the beginning of what can be a new way to significantly slow down the progression of Parkinson’s.

Since GUCY2C appears to protect dopamine neurons in the brain, researchers could explore the possibility of stimulating GUCY2C as a treatment for PD. They could also try increasing cGMP, a byproduct of GUCY2C activation. This could potentially prevent the degeneration of dopamine neurons, a hallmark of the disease.

The study also found that people with PD have high levels of GUCY2C, which may also serve as an early indicator of Parkinson’s.

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

With more research, GUCY2C could be a potential biomarker doctors can use to detect PD earlier. Having access to early biomarkers are critical for early therapeutic interventions for people with PD.

In addition, GUCY2C is a promising therapeutic target to prevent or treat PD. While developing a treatment that targets GUCY2C or its byproducts could take time, it remains important for researchers to identify as many potential treatments as possible. People who are currently experiencing Parkinson’s symptoms should talk to a healthcare provider.

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.

• My PD Story: Scott Waldman, MD, PhD – learn more about this study and Dr. Waldman
• Neuro Talk: PD Progression
• Getting Diagnosed

For most people, being in the hospital is a stressful experience. People are usually sick or experiencing a health issue. For people with Parkinson’s disease (PD), their symptoms may get worse, and new symptoms, like confusion or thinking changes, can develop because of stress, infection, fatigue, sleep disturbances, surgery or new medications.

A new published review of more than 35,000 hospital admissions of people with Parkinson’s found an increased risk of delirium and aspiration pneumonia as potentially avoidable complications. 

As we share in our Hospital Safety Guide, preparation and clear communication can help you minimize complications and recovery time when hospitalized. Understanding the risks you or a loved one with Parkinson’s face and ways to have your needs met can help the hospital care team provide the best possible care. 

Know how to identify Delirium

Delirium is a reversible change in a person's level of attention and concentration. 

Anti-nausea, gastrointestinal and pain medications, which are routinely given before and after surgery, can worsen existing PD symptoms or cause new, temporary symptoms like delirium. Avoiding these medications can decrease your risk of developing delirium.

Additionally, some common treatments for delirium aren’t appropriate for people with PD, and can make Parkinson’s symptoms and the delirium worse. If you or a loved one develop delirium in the hospital, it is important to avoid the antipsychotic medications that are antidopaminergic, meaning they decrease the amount of dopamine in the brain. 

People with Parkinson’s should only be given one of the three antipsychotics that are safe: 

1. Pimavanserin (Nuplazid)
2. Quetiapine (Seroquel)
3. Clozapine (Clozaril). 

All psychotics, with the exception of these three, should be avoided in nearly all circumstances.

Read our list of medications to avoid

Know the signs of Aspiration Pneumonia 

Aspiration pneumonia accounts for 70% of deaths among people with PD, according to an NIH study. 

Aspiration pneumonia is an infection that happens when bacteria from your mouth gets pulled down into the lungs and causes an infection. This can happen after a person aspirates, meaning they swallow the wrong way, and something enters their airways or lungs. Aspiration occurs more frequently when someone has issues with swallowing (dysphagia), which is a common Parkinson’s symptom. 

To prevent aspiration and aspiration pneumonia, people with Parkinson’s need to be screened for swallowing changes, also known as dysphagia, to safely maintain their medication routine and minimize their risk of aspiration pneumonia and weight loss. 

In addition, ensuring that you or your loved one with Parkinson’s get their Parkinson’s medications on time and avoid contraindicated medications that are not safe for people with Parkinson’s can also help prevent the development of new dysphagia or the worsening of mild dysphagia. 

Tips to avoid delirium and aspiration pneumonia in the hospital

Tip 1.  Avoid medications that are not safe for Parkinson’s. 

This can potentially help you to:

• Prevent delirium caused by taking contraindicated anti-nausea medications
• Prevent worsening of delirium caused by taking contraindicated antipsychotic medications

Review the list of harmful medications on the Parkinson’s Care Summary with your hospital care team before surgery and before any new medication is prescribed.

Tip 2. Take medications on time, every time to help prevent new or worsening swallowing challenges. 

If your nurse or speech-language pathologist is concerned about your swallowing ability, discuss safe ways to continue taking your medications, such as with a sip of water or crushed with applesauce.

Use the Medication Form to list all your medications for Parkinson’s and other conditions, including over-the counter medications and supplements in the order that you take them each day. Your list should be clearly labeled with the dosage (usually mg or milligrams) and the specific time that you take each medication.

Download the Medication Form

Tip 3. Tell your nurses if you are having trouble swallowing and ask to see the Speech Language Pathologist (SLP). 

Together, your nurse and SLP can provide safety measures to decrease risks.

You may need to temporarily stop eating and drinking if you have a serious swallowing issue (dysphagia) or are scheduled for a medical procedure that requires fasting. If you or your loved one are instructed you cannot swallow pills, show the nurse and SLP “Other Ways to Take your Medication” to explore potential ways to safely continue taking Parkinson’s medications

If you have swallowing or speech symptoms, we recommend you regularly see a speech language pathologist. Once discharged, ask your doctor for a referral, or call our Helpline at 1-800-4PD-INFO (1-800-473-4636).

Tip 4. Reducing the risk of aspiration pneumonia is a two-part process.

Help reduce aspiration pneumonia when hospitalized and at home that involves (1) preventing swallowing issues and (2) reducing bacteria in your mouth by cleaning your teeth and mouth regularly. Learn more about dental health and Parkinson’s.

Prevent aspiration by eating when PD meds are working and you have energy. It can also help to sit up for meals and take smaller bites. Prevent aspiration pneumonia by brushing your teeth, tongue and mouth before and after eating to reduce bacteria. 

Read more about the steps you can take to avoid delirium, aspiration pneumonia, and other avoidable complications in our Hospital Safety Guide.

Help Spread the Word

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Sleep recharges our brains and bodies, while boosting mental wellness. People living with Parkinson’s disease (PD) need even more time to reset and restore. Discover how Parkinson’s symptoms, medications or other health problems can impact your sleep, and what you can do to maximize slumber.

This article is based on Trouble with Zzz's: Sleep Challenges with Parkinson's, a Parkinson’s Foundation Expert Briefing webinar presented Aleksandar Videnovic, MD, MSc, associate professor of neurology at Harvard Medical School and director for the Massachusetts General Hospital Division of Sleep Medicine and Program on Sleep, Circadian Biology and Neurodegeneration.

Aging, PD and Trouble with Sleep

As people age, it may be harder to fall asleep and waking up at night can be more frequent. Parkinson’s can further disrupt restorative sleep. As many as 80-90% of people with Parkinson’s can experience a sleep problem during the course of the disease.

Parkinson’s-related brain changes upset the circadian system, sometimes called the body’s internal clock. PD also impacts sleep drive — the growing sensation as day turns to night of the need to sleep. Other elements of PD that can disrupt slumber include:

• Parkinson's symptoms, such as tremor or PD-related pain, may emerge overnight as medications wear off. Other symptoms include akinesia (difficulty moving or inability to move), rigidity, dyskinesia (erratic, involuntary movement) and more.
• Medications used to treat PD can interfere with sleep. Others can make it harder to stay alert during the day.
• Depression and anxiety are extremely common PD symptoms. These and other symptoms, such as hallucinations, can keep a person awake at night.
• Changes to the autonomic system, the body’s network for regulating jobs like breathing and blood pressure, impact sleep. Nocturia — excessive nighttime urination — can be common in PD.

Sleep disorders can be exhausting for a person with Parkinson’s, as well as their bed partner. These can include:

• Obstructive sleep apnea and other sleep-disordered breathing can obstruct the airway repeatedly during sleep, resulting in coughing, choking and frequent waking. People with sleep-disordered breathing experience microarousals, waking up to 60 times hourly, without recognizing it. Sleep apnea affects up to 10% of the population, impacting people without Parkinson’s and those with PD with the same frequency.
• Excessive daytime sleepiness (EDS) may make it difficult to stay awake during daylight hours or cause sudden daytime sleep. PD brain changes and symptoms, medication regimens, co-existent sleep disorders and age-related physical changes can all cause EDS. Up to 16% or more of people with PD may experience poor daytime alertness. Some may be unaware of how EDS affects them. A trusted companion can offer honest input. Sometimes, sleep attacks can come on without any warning, significantly impacting a person’s ability to drive safely.
• Restless legs syndrome (RLS), an uncomfortable feeling in the legs or feet and irresistible need to move, can impact some people even prior to a PD diagnosis. However, not everyone with Parkinson’s experiences RLS, nor will most people who experience RLS go on to develop PD.
• Rapid eye movement (REM) sleep behavior disorder (RBD): People dream and experience muscle relaxation during REM stage of sleep. RBD can affect up to half of people with Parkinson’s, impacting muscle relaxation and causing people to act out their dreams — talking, yelling or moving about.

Like restless legs syndrome, RBD can begin long before a Parkinson’s diagnosis. Although not everyone who lives with RBD will develop Parkinson’s, their risk of developing PD or Dementia with Lewy Bodies — diagnosed when cognitive decline happens before or alongside motor symptoms  —  is significantly higher. This is meaningful for Parkinson’s research.

As potential therapies evolve to slow PD progression, there may be a window of opportunity for preventative intervention in people who experience REM sleep behavior disorder but have yet to develop a neurodegenerative disease.

Management Strategies for Fragmented Sleep

Talk to your healthcare provider about sleep issues, fatigue or daytime sleepiness. Your doctor may ask questions about your sleep history. A careful review of each or your medications will help your doctor determine whether a simple adjustment or addition might improve slumber:

• Long-acting levodopa or additional levodopa is sometimes prescribed for bedtime use.
• Catechol-O-methyl transferase (COMT) is an enzyme in the body. It can impact the effectiveness of levodopa. COMT inhibitors prolong the benefits of levodopa. These are primarily used for wearing off (changes in the ability to move between doses of levodopa) but are sometimes also prescribed with levodopa for use at night.
• People taking diuretics might be directed to use them earlier in the day. Likewise, limiting the use of PD medications selegiline and amantadine later in the day might improve insomnia.
• Anticholinergic medications are sometimes used for nocturia, however, cognitive slowing can be a side effect. These can also cause confusion and hallucinations and are not recommended in older people.
• Caffeine and some stimulant medications can promote alertness during the day.

Mental wellness: Talk to your doctor about symptoms of depression or other emotional challenges. Parkinson’s impacts areas of the brain that regulate mood, sleep, energy and more. Caring for mental health also benefits sleep.

Sleep disorders: If your doctor suspects a sleep disorder such as obstructed breathing, restless legs or RBD, you might be referred for a sleep study in a sleep clinic.

• Sleep apnea treatment may require a dental appliance or a continuous positive airway pressure (CPAP) machine that is worn when sleeping or napping.
• Dopamine agonists — medications that rouse areas of the brain motivated by dopamine — benzodiazepines, opioids and a class of medications known as calcium channel alpha-2 delta ligands, such a gabapentin, are sometimes used for restless legs syndrome. Dopamine-blocking, anticholinergic and antihistamine medications should be avoided for RLS.
• Your doctor may recommend melatonin or the medication clonazepam for RBD. While antidepressants may help with some aspects of insomnia, some can unmask or worsen RBD.

Tips to Improve Shut-eye

A healthy sleep routine — sometimes called sleep hygiene — is another key component to a good night’s rest. Try these small changes that can make a big difference:

• Exercise regularly (aim for early in the day) to improve sleep quality and overall function.
• Limit naps: a short snooze earlier in the day, of 30 minutes or less, is less likely to interfere with nighttime sleep. 
• Avoid stimulants, such as caffeine, later in the day.
• Minimize your screen time before bed. Avoid screens entirely — including TV and mobile devices — in the bedroom.
• Go to sleep and rise at the same time, weekdays and weekends.
• Turn the lights out: light regulates the body’s clock, signaling that it is time to wake.
• Employ motion-detecting nightlights to safely guide you to the bathroom.
• Sleep in a wider bed that is lower to ground. This can minimize injuries and lessen the impact in case of an accidental fall.
• Consider a bedside rail to prevent falls; a bedside commode can also be helpful for people who have difficulty getting to the toilet at night.
• Use satin or silk sheets or pajamas to make it easier to turn in bed.

Adequate hydration can improve PD symptoms, boosting low blood pressure and easing constipation. However, drinking liquids too close to bedtime can cause frequent nighttime urination. Minimize beverages a few hours before bed.

Research

Light hitting the eyes is one of the biggest environmental factors regulating the circadian system. The timing of meals, exercise, naps and rest also influences our body clock. In turn, this timer regulates our mood, behavior, immune response and more. Researchers are exploring ways to improving circadian system function in PD.

Light therapy shows great promise as a noninvasive, widely available, nonpharmacological treatment to ease non-movement symptoms of Parkinson’s, including fatigue, sleep issues and mood changes.

In a 2017 JAMA Neurology journal study, Videnovic et al. found that exposure to bright light (10,000 lux) or dim-red light (less than 300 lux) — twice daily in one-hour sessions over two weeks — improved daytime alertness and sleep quality.

Those findings were carried over into the recently completed ENLITE PD trial conducted at 25 sites across North America. The study analyzes the effect of daily light therapy on PD symptoms, including sleep. At the time of this Expert Briefing, the study’s authors were preparing to submit their findings for publication, with the aim of conducting a phase III clinical trial.

Learn More

To learn more about Parkinson’s and sleep explore these resources:

• Parkinson’s Disease and Sleep
• Sleep Disorders
• Care Partner Deep Dive: Three Experts Discuss Sleep, Cognition and Mood in Parkinson's