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

Share this graphic on Facebook to help your friends and family with Parkinson's stay safe in the hospital.

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

The National Parkinson’s Project is a first-ever federal initiative to prevent and cure Parkinson’s disease, treat its symptoms and slow or stop its progression. The National Parkinson’s Project is being carried out under the National Plan to End Parkinson’s Act, by the Secretary of Health and Human Services (HHS).

What’s Next

The U.S. Department of Health and Human Services is building a supporting advisory council to develop the National Parkinson’s Project. This is a collaborative effort, as government agencies and leaders in the PD space, including the Parkinson’s Foundation, will provide essential community input and planning support.

The National Parkinson’s Project will encompass research, care, and services for Parkinson’s and all other neurodegenerative Parkinsonisms, including multiple system atrophy, corticobasal degeneration, progressive supranuclear palsy, and Parkinson’s-related dementia.

To receive updates on the Act, please sign up for the NIH listserv.

January 2025 Update

National Plan to End Parkinson's Update: NIH Seeks Nominations for Advisory PD Council

The National Institutes of Health (NIH) has received a delegation of authority to lead the implementation of the Dr. Emmanuel Bilirakis and Honorable Jennifer Wexton National Plan to End Parkinson’s Act, which was signed into law on July 2, 2024. Along with the HHS Office of the Assistant Secretary for Health (OASH), the National Institute of Neurological Disorders and Stroke (NINDS), part of NIH, will co-chair the Advisory Council on Parkinson’s Research, Care, and Services called for in this Act.

The NIH, with support from OASH and in collaboration with the Council, will create, maintain, and periodically update a National Plan to prevent, diagnose, treat and cure Parkinson’s, as well as stop disease progression.

The National Plan will encompass research, care, and services for Parkinson’s disease (PD) and all other neurodegenerative Parkinsonisms, including multiple system atrophy, corticobasal degeneration, progressive supranuclear palsy, and Parkinson’s-related dementia.  

To receive updates on the Act, please sign up for the NIH listserv.

September 2024 Update

President Biden Signs Parkinson's Bill into Law 

How to Make an Impact on Parkinson’s National Day of Action

On September 17, 2024, thousands of policy advocates across the country will virtually rally together to urge elected officials to take steps to better understand and address environmental risk factors for Parkinson’s disease (PD).

Led by the Unified Parkinson’s Advocacy Council, the Parkinson’s National Day of Action is entirely virtual, and it only takes a few minutes to participate! On September 17:

1. Sign a petition to the White House urging them to ban paraquat, a harmful herbicide thought to increase Parkinson’s risk by as much as 500%.
2. Call your member of Congress to ask them to cosponsor the HEALTHY BRAINS Act (H.R. 9233). This new bill would direct the federal government to research environmental risk factors for neurodegenerative diseases like Parkinson’s.
   • Call Congress directly from your phone by looking up your senators’ and representatives’ office numbers online or by calling the U.S. Capitol Hill switchboard at 202-224-3121 and ask to be connected to their offices.

More than 1 million Americans live with Parkinson’s, the second most common and fastest growing neurological disease. Help us get closer to a cure by participating in the Parkinson’s National Day of Action!

July 2024 Update

On July 2, 2024, President Biden signed the National Parkinson's Project into law. This is the first-ever federal legislation dedicated to ending Parkinson’s disease (PD).

Top five ways this monumental bill can make an impact:

1. Dramatically increase federal research funding
2. Develop more effective pathways for treatments and cures
3. Improve early diagnosis
4. Spark new and improved models for patient care
5. Address health disparities in diagnosis, treatment and clinical trial participation

“The Parkinson’s Foundation is excited for what comes next,” said John Lehr, Parkinson’s Foundation President and CEO. “We look forward to having input in designing exactly how this bill will mobilize meaningful change for the one million Americans living with this disease.”

The Parkinson’s Foundation would like to thank all the PD advocates, volunteers and people who wrote to their senators and representatives to make this bill to become law. We also thank President Biden and members of the U.S. Senate and House of Representatives for helping us make PD history.

Spread the word!

Share this monumental victory on your social media channels! Get friends and family excited that Parkinson’s disease has received legislative support.

Share the news on social media. Click here.

Timeline at a Glance:

• July 2, 2024: President Biden signs the National Parkinson's Project S.1064/H.R.8585), the first-ever federal legislation dedicated to ending Parkinson’s.
• May 23, 2024: U.S. Senate passes the Act.
• December 14, 2023: U.S. House of Representatives passes the Act.
• March 29, 2023: the Act is reintroduced in the House and Senate for the 2023 session.

What’s Next?

Follow us on social media (Facebook, X, Instagram and others) to stay up to date on what happens next. We are excited to document the process and any movement spurred by the new Act and our involvement alongside the Michael J. Fox Foundation and other leaders in the PD space to establish next steps.

May 2024 Update

On May 23, 2024, the U.S. Senate unanimously passed the National Plan to End Parkinson’s Act, the first-ever federal legislation dedicated to ending Parkinson’s disease (PD). Next, the bill will be sent to President Biden’s desk to be signed into law. The bill passed with overwhelming bipartisan support in the U.S. House of Representatives in December.

“As we eagerly await the bill to be signed into law, we applaud members of congress for their bipartisan support and recognition of one of the most pressing health care issues of our day,” said Parkinson’s Foundation President and CEO John L. Lehr. “On behalf of the Parkinson’s Foundation, I’d like to thank members of the United States Congress for joining the Michael J. Fox Foundation for Parkinson’s Research, the Unified Parkinson's Advocacy Council and the greater PD community in the fight against Parkinson’s disease.”

This monumental bill has the potential to shape the lives of the one million Americans living with Parkinson’s. It is designed to:

• Dramatically increase federal research funding
• Develop more effective pathways for treatments and cures
• Improve early diagnosis
• Spark new and improved models for patient care
• Create standards and measures to prevent Parkinson’s disease
• Address health disparities in diagnosis, treatment and clinical trial participation
• Enhance public awareness of the disease

Timeline at a Glance:

• On May 23, 2024, the U.S. Senate passed the National Plan to End Parkinson’s Act S.1064/H.R.8585), the first-ever federal legislation dedicated to ending Parkinson’s.
• On December 14, 2023, the Act passed through the U.S. House of Representatives.
• On March 29, 2023, the Act was reintroduced in the House and Senate for the 2023 session.

What’s Next?

Once President Biden signs the bill into law, the Federal government will begin to establish actionable steps to carry out the plan. The Parkinson’s Foundation looks forward to working alongside the Michael J. Fox Foundation and other leaders in the PD space to help throughout this process.

Content provided by The Michael J. Fox Foundation for Parkinson’s Research (MJFF). Read the MJFF blog article here.

December 2023 Update

Congress Reintroduces the National Plan to End Parkinson’s Act

On December 14, 2023, The National Plan to End Parkinson’s Act (S.1064/H.R.8585) passed through the U.S. House of Representatives. Next, the bill will go to the U.S. Senate. 

Now is the time to have all of your members of Congress sign on to support the bill so it will pass this session!

Your senators and representatives need to hear from members of the Parkinson’s community about why we need a focused, national strategy to prevent Parkinson’s, find a cure, and ensure those living with the disease can access care.

Specifically, we encourage members of the Parkinson’s community in the U.S. to Call Your Members of Congress.

• Call Congress directly from your phone by looking up your senators’ and representatives’ office numbers online or by calling the U.S. Capitol Hill switchboard at 202-224-3121 and asking to be connected to their offices.

VIEW THE CALL SCRIPT

On July 28, 2022, the U.S. House of Representatives introduced the first-ever legislation solely devoted to ending Parkinson’s. This is a historic moment for the Parkinson’s community!

The National Plan to End Parkinson’s Act will, for the first time, unite the federal government and private enterprises in a mission to prevent and cure Parkinson’s, alleviate financial and health burdens on American families, and ensure those living with the disease have access to the care they need.

This bipartisan legislation is led by Representative Paul Tonko (D-NY) and Representative Gus Bilirakis (R-FL). The Parkinson’s community is thankful for its leadership.

Now what?

This bill will go through the traditional congressional process and will need to be voted on by the House. A Senate’s companion bill will be introduced in the coming weeks, because it is standard congressional procedure for both chambers of Congress to pass the bill before it can go to the President for signature.

Why a national plan and why now?

Parkinson’s is a disease that requires a national effort to cure and prevent. Parkinson’s costs the U.S. $52 billion every year, half of which is shouldered by the federal government, and that annual cost is expected to grow to $80 billion by the year 2037.

A national plan to end Parkinson’s has the potential to:

• Dramatically increase federal research funding
• Develop more effective pathways for treatments and cures
• Improve early diagnosis
• Spark new and improved models for patient care
• Create standards and measures to prevent Parkinson’s disease
• Address health disparities in diagnosis, treatment and clinical trial participation
• Enhance public awareness of the disease

The public-private advisory council created as part of this legislation will report every year to Congress on their progress and impact in ending Parkinson’s. This is the kind of forward-looking strategy and responsible accountability the Parkinson’s community needs and deserves.

The Parkinson’s Foundation is a member of the Unified Parkinson’s Advocacy Council (UPAC), a collection of nearly 30 Parkinson’s organizations that come together to help shape federal and state public policy in ways that support the Parkinson’s community. There will be many opportunities for all of us to engage our Members of Congress on this legislation and have conversations about the bill and its intended impact, and we will begin to communicate those opportunities in the coming weeks.

Content provided by The Michael J. Fox Foundation

We will update this blog and our social media channels as the legislation advances, so stay tuned! Follow us on Facebook, Instagram and Twitter.

Though there is still a lot we don’t know about Parkinson’s disease (PD), therapies aimed at modifying disease progression are poised for major breakthroughs. Researchers are excited about the potential of current studies to improve, slow or someday stop PD.

This article is based on Research Update: Working to Halt PD, a Parkinson’s Foundation Expert Briefing webinar presented by Lorraine Kalia, MD, PhD, FRCPC, assistant professor in the Division of Neurology, Department of Medicine at the University of Toronto and scientist at Toronto Western Research Institute and Tanz Centre for Research in Neurodegenerative Disease.

Understanding PD Progression

Parkinson’s is not a static condition — it's an intricate, progressive disease that evolves over time. Uncovering its many complexities is one of the challenges PD researchers face as they work toward halting its progression.

As people age, the loss of some brain cells is expected. In Parkinson’s this loss happens at a much faster rate. Neurodegeneration, the progressive loss of neurons that produce dopamine — a feel-good chemical related to movement, mood and more — is tied to movement and non-movement symptoms that develop in PD. As time progresses, new symptoms may develop or worsen.

Right now, we have therapies that can treat Parkinson’s symptoms — lessening tremor, easing mobility, improving mood and more — but we can’t stop the disease. Research is at the beginning stages of discovering disease-modifying therapies that might slow or stop the loss of dopamine-producing neurons.

Exploring Disease-Modifying Therapies

Therapies that can potentially change the course of Parkinson’s are rapidly evolving. A 2023 analysis of 139 PD drug therapy clinical trials registered as active on the ClinicalTrials.gov website showed 76 were investigating symptomatic treatments and another 63 were exploring disease-modifying therapies.

Though these therapies are still on the horizon for use in PD, the first drug to change the course of multiple sclerosis (MS) — a condition that affects a person’s spinal cord and brain and spine — was discovered in 1993. Now, there are more than 20 disease-modifying therapies for MS. One reason medications to slow MS progression have been so successful is that scientists have a way to identify the disease and observe its response to therapies. This is known as a biomarker.

Researchers are beginning to discover possible biomarkers related to Parkinson's. PD is tied to the abnormal clumping of a protein called alpha-synuclein in the brain. Alpha-synuclein can act as a biomarker in PD. Reliable biomarkers can potentially lead to the ability to diagnose Parkinson’ sooner, track disease progression and help researchers design and test therapies that might change the course of the disease.

Changing the Course of PD

Neurodegeneration in Parkinson’s — progressive damage to normal, healthy brain cells — can cause cell dysfunction and death. This process may be reversible. Cell protection is an approach that seeks to slow or prevent this process.

Areas of research that focus on cell protection are expected to show the most progress in the near future. They include:

Exercise

One of the most important PD symptom management tools, it improves heart, muscle and bone health, lung function, as well as cognitive and mental health. Exercise can also reduce the risk of fractures and falls. Research shows it can also help maintain movement in Parkinson’s, slow disease progression and improve symptoms; it may also provide cell protection.

Studies suggest exercise might reduce inflammation in PD and increase growth factors — proteins that stimulate cell growth and influence how a cell functions.

Alpha-synuclein

This protein is abundant in the brain. Though it’s unclear why, alpha-synuclein malfunctions in PD and the proteins start to misfold and stick together, forming increasing buildups. These ultimately form Lewy bodies.

Brain cells are complex and require several healthy components to function. Researchers think malformed alpha-synuclein can disrupt these cell functions and can impact nearby brain cells. Targeting misfolded alpha-synuclein may protect brain cells from dying. There are many potential ways to do this. Researchers are currently exploring prescription therapies that could:

• Reduce alpha-synuclein production in the cell (Buntanetap ION464.)
• Degrade corrupt alpha-synuclein (Minzasolmin.)
• Reduce or prevent problematic alpha-synuclein moving from one cell to another (Prasinezumab ACI-7104.056 and UB-312.)

GBA1 and LRRK2 Genes

There is a connection between genetics and Parkinson’s. GBA is the most common Parkinson's-related gene, occurring in 5 to 10% of people with PD. Carriers may experience PD symptoms at an earlier age compared to those who do not have a genetic form of PD. LRRK2 is involved in about 5% of people with a family history of Parkinson’s. Carriers may have milder symptoms of dementia and depression. 

Lysosome, one of the disposal systems of the cell, is an enzyme that breaks down and gets rid of waste. One thing it may get rid of is alpha-synuclein. GBA lives within the lysosome. In people with a GBA gene mutation, the lysosome enzyme may be underactive. Researchers are currently exploring prescription therapies that could enhance lysosome activity and make it work better.

In Parkinson’s, a LRRK2 mutation impacts the autophagy lysosomal pathway, another cell waste disposal system, causing overactivity. Slowing this activity might reduce neurodegeneration. BIIB094 and BIIB122, intended to curb this excess activity, are currently in clinical trial.

Repurposing Existing Drugs

Therapies already approved for other diseases may hold great potential in Parkinson’s. If proven effective, they can be fast-tracked to begin treating people with PD because they have already gone through clinical trials to demonstrate their safety.

More than one-third of the drugs in current PD clinical trials being tested as potential disease-modifying therapies are repurposed drugs.

Amantadine is an example of drug repurposing in Parkinson’s as it was originally developed as a flu treatment. In the 1960s, a woman with PD taking amantadine for the flu told her doctor her Parkinson’s symptoms felt much better. Subsequent clinical trials confirmed the benefits of amantadine on some PD symptoms. The medication was initially prescribed for movement symptoms, before levodopa became the most effective, widely available Parkinson’s drug. Today, amantadine is primarily used to treat dyskinesia.

Ambroxol is currently approved as a cough suppressant and is in clinical trial to enhance GBA activity. It has quickly moved from Phase II onto Phase III clinical trials.

GLP-1 receptor activators are another category of medications that may hold major disease-modifying potential, are currently making headlines. These drugs were primarily developed for diabetes (one of the most familiar brand names in the category is Ozempic).

GLP-1 receptor activators bind to a receptor on the outside of a cell, causing a chain of activities that can potentially improve memory, cell survival and effects of mitochondria, while reducing inflammation and alpha-synuclein. Exenatide is the first of these to be tested. Various versions of it, NLY01 (slow-release) and PT320 (pegylated), have been or are in clinical trials.

Two related medications, Liraglutide and Lixisenatide, have been or are also in clinical trials. The results of a phase II trial of Lixisenatide published in the April 3, 2024 New England Journal of Medicine are causing a lot of excitement. Lixisenatide therapy in participants with early PD resulted in less motor disability progression than placebo at 12 months. The study is poised to move on to a phase III trial.

Cell Replacement

Early studies to investigate whether brain cells could be replaced in Parkinson's isolated and removed dopamine-making stem cells from human fetal tissue and grafted them into the brains of research participants with PD. While the research showed promise, nuances and complications limited long-term research.

Remarkable advances in stem cell technology over the past decade have led to the ability to make dopamine-producing cells from a person’s blood or skin cells or from embryonic stem cells, unlocking a new generation of stem cell research. There are ongoing clinical trials in countries around the world, including the U.S., investigating potential benefits in Parkinson's.

Cautious Optimism

Parkinson's disease looks different for different people. Different causes may spur its development. Multifaceted research is essential to moving forward.

Science must keep an open mind, follow the evidence and — when disease-modifying treatments become available — target people with the right treatments at the most impactful stages of the disease.

Ultimately, Parkinson’s is a global disease with symptoms and a rate of progression that is unique to each person living with it. It is important to pursue different avenues of research because there may be more than a single cure.

Learn More

The Parkinson’s Foundation works improve care for people with PD and advance research toward a cure.

• Discover how we are working to close gaps in knowledge about PD: Advancing Research
• Explore ongoing Parkinson’s research studies: Join A Study

Learn about PD GENEration — a global genetics study that provides genetic testing and counseling at no cost for people with Parkinson’s.

Vivir bien con la enfermedad de Parkinson (EP) significa obtener el apoyo que necesita: desde herramientas que le ayuden a trabajar junto con su equipo de atención médica hasta recursos que lo empoderen. La Parkinson’s Foundation es su aliada de confianza para obtener información que puede ayudarle a navegar por cada etapa de esta enfermedad.

¿Sabía que nuestros 7 recursos principales están disponibles en inglés y español? Explore a continuación estos recursos diseñados para ayudar a facilitarle un poco más la vida a las personas con la enfermedad de Parkinson, a sus cuidadores y a sus familiares:

1. Línea de Ayuda

Llame al 1-800-4PD-INFO (1-800-473-4636), opción 3 para español o envíe un correo electrónico a Helpline@Parkinson.org para hacer sus preguntas sobre la EP a un especialista de la Línea de Ayuda, de lunes a viernes de 9 a.m. a 7 p.m., hora del Este.

Contactar a la Línea de Ayuda en inglés    Contactar a la Línea de Ayuda en español

2. Parkinson.org/Espanol

Visite nuestro sitio web para consultar un número ilimitado de artículos dedicados a la información más reciente sobre el Parkinson. Consulte nuestras páginas más populares: 10 signos,  Etapas del Parkinson y Levodopa.

Leer más en inglés    Leer más en españOL

3. Eventos en línea

Inscríbase a un evento en línea diseñado para usted. ¿Listo para aprender algo nuevo ahora mismo? Explore nuestra impresionante colección de eventos grabados:

• Concéntrese en su salud mental con los Lunes de Atención Plena
• Aprenda algo nuevo de un experto en la EP con Miércoles de Bienestar
• Muévase con una clase de ejercicio a la carta adaptada para la EP con los Viernes de Ejercicio

Ver eventos en inglés    Ver eventos en español

4. Biblioteca de la EP

Lea información detallada acerca de la EP en nuestra colección de publicaciones gratuitas. Adéntrese en nuestros mejores contenidos en español: El libro Cuidado y manejo, la hoja informativa Fatiga y trastornos del sueño y nuestras Recomendaciones de ejercicio.

Visitar nuestra Biblioteca de la EP en inglés    Visitar nuestra Biblioteca de la EP en español

5. Videos

Descubra nuestro Canal en Español: Recursos para ti, canal de YouTube. Comience con

• Los 5 mitos respecto de participar en ensayos clínicos
• Playlist: Programa de cuidadores

Ver videos en inglés    Ver videos en español

6. Podcast

Hablamos de lo último en la investigación, el ejercicio y los tratamientos de la EP a lo largo de nuestra serie de podcast. Los episodios más populares en español incluyen Los beneficios de la fisioterapia y Dónde acudir para obtener recursos y apoyo como cuidadores. Suscríbase ahora.

Escuchar ahora en inglés    Escuchar ahora en español

7. Blog

Visite nuestro blog para leer artículos que destacan los temas más recientes sobre el Parkinson: desde investigaciones hasta consejos para ayudarle a vivir mejor con el Parkinson.

Leer más en inglés     Leer más en español

Recuerde participar con nosotros en este Mes de la Concientización sobre el Parkinson compartiendo su ABC de la EP y lea nuestras ideas para publicaciones en redes sociales en nuestro kit de herramientas en español.

A clinical trial shows that an ultrasound treatment can help with involuntary and impaired movement for people with Parkinson’s.

People with Parkinson’s disease (PD) experienced significant improvement in tremors, mobility, and other movement symptoms after undergoing a minimally invasive procedure using focused ultrasound, a study published in the New England Journal of Medicine shows.

Deep brain stimulation (DBS) has become the main surgical treatment for people with PD who do not fully respond to levodopa. It involves the invasive surgical placement of tiny wires into the targeted brain area, which is then stimulated by sending electrical signals through the wires. Focused ultrasound is a treatment that emits high-intensity sound waves into the brain, guided by magnetic resonance imaging (MRI). Where these waves cross, they create high energy, which creates heat, destroying a specific area in the brain connected to tremor. It is considered non-invasive because it does not involve incisions or holes in the skull.

Both treatments have pros and cons.

• Focused ultrasound is non-invasive. It does not require additional adjustments and creates a permanent change.
• DBS is an invasive surgery that allows for adjustments as movement symptoms worsen through the course of Parkinson’s, even years after surgery. DBS can still be an option for those who undergo focused ultrasound if the disease continues to progress.

The U.S. Food and Drug Administration (FDA) approved focused ultrasound as a Parkinson’s treatment for those with movement symptoms mainly on one side of the body. However, most people with Parkinson’s have movement symptoms on both sides of the body. This study included people who have symptoms on both sides of the body.

About the Study & Results

The focused ultrasound targets a part of the brain called the globus pallidus internus (GPI), which is part of the basal ganglia, a network of brain structures that controls movement. In Parkinson’s, the loss of dopamine-producing neurons disrupts the normal functioning of the basal ganglia. This can ultimately lead to abnormal activity in the GPI and can contribute to the movement symptoms of Parkinson’s.

This study examined the safety and efficacy of focused ultrasound of the GPI in a randomized trial of 94 participants with PD movement symptoms. Only the side of the brain opposite the participant’s most symptomatic side was treated. Of the 94 participants, 69 were randomly selected to undergo the procedure, with 25 receiving the false treatment as a control.

Each participant received a clinical assessment for the severity and progression of their Parkinson's before and after treatment. Nearly 70% of participants in the treatment group had improvements in symptoms after three months of follow-up, compared to 32% in the control group who had an inactive procedure without focused ultrasound.

One year later, a follow-up assessment tracked 60 of the original 69 participants and found that 66% of those who received treatment and initial improvement in symptoms continued to have a positive response to the treatment. Additionally, of the 25 participants who initially had a placebo treatment, 20 chose to undergo treatment three months later. Of the 20 that chose treatment, 70% had a positive response at three months, and 57% had continued success one year later.

A third of the participants had no side effects. Among those who did, most participants experienced only some mild to moderate symptoms, including headaches, dizziness and nausea. However, one person experienced a serious complication related to the procedure: a nonfatal pulmonary embolism. At the three months check-up, adverse reactions were mild to moderate and included slurred speech, disturbances in walking, loss of taste, visual disturbance and facial weakness. 

Highlights

• The clinical trial used focused ultrasound to target movement symptoms of participants with Parkinson’s with the goal of improving them.
• Nearly 70% of participants in the treatment group responded successfully to treatment after three months of follow-up, compared to 32% in the control group who did now undergo the focused ultrasound.
• About 66% of participants in the treatment group who had initial success continued to have a positive response from the treatment a year later.

What does this mean?

This treatment may be effective for improving physical symptoms of Parkinson’s. However, the long-term effects of the procedure are still not known. All participants in the study will be followed for five years to assess the effects and long-term safety of the procedure.

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

Although approved by the FDA, it will be years before we know the long-term effectiveness and impacts of focused ultrasound as a PD treatment. The Parkinson’s Foundation encourages people with PD to work with a movement disorders specialist to make sure a focused ultrasound is a good option.

There are an increasing number of sites offering focused ultrasound for Parkinson’s across the country. For a list of sites that offer the treatment, visit the Focused Ultrasound Foundation website. Be sure to ask about the site’s experience with treating Parkinson’s disease, specifically.

Of note, focused ultrasound is not universally covered by Medicare — eligibility and region vary when it comes to Medicare reimbursement. It will take time for the procedure to become more widely available and to be covered by insurance. Directly contact the center offering focused ultrasound in your area for specific information about insurance coverage.

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 below, or by calling our free Helpline at 1-800-4PD-INFO (1-800-473-4636) for answers to your Parkinson’s questions.

• Other Surgical Options
• Non-pharmaceutical Treatments for PD: DBS and Focused Ultrasound
• Surgical Options: A Treatment Guide to Parkinson's Disease - Updated