Discovery Illuminates How Parkinsons Disease Spreads In The Brain
A person with Parkinson’s disease visiting the doctor. Credit: Shutterstock
Aggregates of the protein alpha-synuclein spread in the brains of people with Parkinsons disease through a cellular waste-ejection process, suggests a new study led by Weill Cornell Medicine researchers.
During the process, called lysosomal exocytosis, neurons eject protein waste they cannot break down and recycle. The discovery, published Aug. 22 in Nature Communications, could resolve one of the mysteries of Parkinsons disease and lead to new strategies for treating or preventing the neurological disorder.
Our results also suggest that lysosomal exocytosis could be a general mechanism for the disposal of aggregated and degradation-resistant proteins from neuronsin normal, healthy circumstances and in neurodegenerative diseases, said study senior author Dr. Manu Sharma, an assistant professor of neuroscience in the Feil Family Brain and Mind Research Institute and Appel Alzheimers Disease Research Institute at Weill Cornell Medicine.
In the study, Dr. Sharma and his team, including co-first author Ying Xue Xie, a doctoral candidate in the Weill Cornell Graduate School of Medical Sciences, showed with detailed studies of Parkinsons mouse models that alpha synuclein aggregatescapable of spreading and causing neurodegenerationoriginated within neurons. These aggregates, they found, then accumulate within capsule-like waste bins in cells called lysosomes.
What Is Fetal Cell Transplantation
Fetal cell transplantation is a procedure in which fetal cells are implanted into the brains of people with Parkinson’s disease to replace the dopamine-producing cells in the substantia nigra. Although promising, this area of research is one of the most controversial. Some studies have found that fetal cell transplantation caused an increase in severe involuntary movements due to too much dopamine in the brain. There are also moral and ethical objections to the use of fetal cell implants. As a result, other methods of treatment are being explored.
Apda Center For Advanced Research
Boston University School of Medicine is home to an Advanced Center for Parkinsons Research supported by the American Parkinson Disease Association. The Center is directed by Marie Hélène Saint-Hilaire, MD, FRCPC, with a comprehensive team of experts.
APDA Centers for Advanced Research must meet the highest academic standards and be distinguished leaders in the field of PD research. There are eight such centers across the country.
The funding of this Center supports a large research program, which includes: Biomarker studies, studies of non-motor symptoms, studies of self-management strategies, an active clinical trials program, 3500 patient visits per year, a Deep Brain Stimulation program, and a fellowship program in Movement Disorders.
Parkinsons disease affects more than 1 million people in the United States annually, with at least 60,000 new cases diagnosed each year. The chronic and progressive neurological condition is the second most common neurodegenerative aging disorder, after Alzheimers disease.
For more information contact:
Medical Director: Marie-Hélène Saint Hilaire, MD, FRCPPhone: 800-651-8466
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Researchers Discover 50 Novel Parkinson’s Disease Candidate Genes Using An Innovative Integrated Functional Genomics Approach
- Date:
- Texas Children’s Hospital
- Summary:
- A study has used a multidisciplinary high-throughput functional genomics approach to identify and functionally validate dozens of genes that could cause or protect against Parkinson’s disease.
Many neurodegenerative disorders such as Parkinson’s disease result from the combined effects of mutations in several genes . Although previous studies have identified a few genes that are responsible for familial or sporadic cases of PD, we are still far from knowing the entire spectrum of genes that contribute to this complex disorder. Researchers at the Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital and Baylor College of Medicine have recently developed an integrated functional genomics approach that led to the discovery of 50 genes that have been shown for the first time to modify PD pathology in a disease animal model. The study was published in Human Molecular Genetics.
The study was led by Dr. Juan Botas, professor at Baylor College and investigator at the Duncan NRI. The highlight of the study is a new multidisciplinary high-throughput approach the team developed to identify and functionally validate dozens of PD-causing and neuroprotective genes.
To speed up the gene validation process, the lead author of this study, graduate student, Jiayang Li, and others developed a multi-step approach that combined several computational and in vivo validation methods.
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New Research Explores The Possibilities Biomarkers Offer In Early Detection Accurate Diagnosis And Effective Treatment For Parkinsons Disease
Parkinsons disease affects nearly 1 million people in the United States. We expect that number to grow to 1.2 million by 2030. In our recent webinar, Matt Stern, MD, a renowned expert in the field of Parkinsons disease, shared updates on the current state of Parkinsons research. He also discussed ongoing research and new discoveries that offer hope for people suffering from Parkinsons and other neurodegenerative diseases.
Dr. Stern is a professor of neurology, co-founder of the Parkinsons Disease and Movement Disorder Center at the University of Pennsylvania, and founding director of the Parkinsons Disease Research, Education and Clinical Center at the Pennsylvania VA Medical Center.
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How Is Parkinsons Disease Treated Or Cured
Although no treatment restores damaged neurons, medications can moderate the symptoms of Parkinsons disease. The most common, a combination medication called carbidopa-levodopa in its generic form, works directly on the dopamine supply in the brain.
While the levodopa converts into dopamine in the brain, the carbidopa prevents it from breaking down and allows more of it to be converted. This supports the brains natural absorption and use of dopamine, which improves voluntary control of body movement.
Several other medications may be used, either long-term or in the diseases later stages.
A surgical procedure called deep brain stimulation helps some patients as Parkinsons gets more severe. In this procedure, electrodes are implanted into the brain. A doctor can fine-tune the electrical signals sent by these devices to reduce day to day symptoms.
Some lifestyle changes can help patients maintain quality of life and manage symptoms. Many doctors recommend Parkinsons patients undertake ongoing aerobic exercise.
Stretching can improve balance and coordination, making falls less likely. For those who experience speech issues, therapy with a speech language pathologist can maintain abilities.
Patients should become familiar with common mobility aids and consider changes to make the home environment safer, such as grab bars in the tub to reduce the risk of falling.
What Should I Know Before Participating In A Clinical Study
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Nerve Damage Seen In Skin Can Predict Parkinsons Progression
In Parkinsons patients, greater nerve damage in the skin around the ankle is significantly associated with subsequent progression of motor symptoms, while the presence of such damage in neck skin is linked to progressive cognitive decline, a study shows. Notably, this nerve damage progression was not related to increased
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Complementary And Supportive Therapies
A wide variety of complementary and supportive therapies may be used for PD, including:
A healthy diet. At this time there are no specific vitamins, minerals, or other nutrients that have any proven therapeutic value in PD. The National Institute of Neurological Disorders and Stroke and other components of the National Institutes of Health are funding research to determine if caffeine, antioxidants, and other dietary factors may be beneficial for preventing or treating PD. A normal, healthy diet can promote overall well-being for people with PD just as it would for anyone else. Eating a fiber-rich diet and drinking plenty of fluids also can help alleviate constipation. A high protein diet, however, may limit levodopas absorption.
Exercise. Exercise can help people with PD improve their mobility, flexibility, and body strength. It also can improve well-being, balance, minimize gait problems, and strengthen certain muscles so that people can speak and swallow better. General physical activity, such as walking, gardening, swimming, calisthenics, and using exercise machines, can have other benefit. People with PD should always check with their doctors before beginning a new exercise program.
Alternative approaches that are used by some individuals with PD include:
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Exploring Seven Recently Approved Parkinsons Treatments
Remarkably, in the last five years, seven new medications have been approved for the treatment of the motor symptoms of Parkinsons disease , with two approved in 2020. Thats exciting progress! And while it is great to have so many choices, the various options can be confusing so today I will describe these new medications and their uses.
Symptoms Of Parkinsons Disease
Parkinsons has four main symptoms:
- Tremor in hands, arms, legs, jaw, or head
- Muscle stiffness, where muscle remains contracted for a long time
- Slowness of movement
- Impaired balance and coordination, sometimes leading to falls
Other symptoms may include:
The symptoms of Parkinsons and the rate of progression differ among individuals. Early symptoms of this disease are subtle and occur gradually. For example, people may feel mild tremors or have difficulty getting out of a chair. They may notice that they speak too softly, or that their handwriting is slow and looks cramped or small. Friends or family members may be the first to notice changes in someone with early Parkinsons. They may see that the persons face lacks expression and animation, or that the person does not move an arm or leg normally.
People with Parkinson’s disease often develop a parkinsonian gait that includes a tendency to lean forward take small, quick steps and reduce swinging their arms. They also may have trouble initiating or continuing movement.
Symptoms often begin on one side of the body or even in one limb on one side of the body. As the disease progresses, it eventually affects both sides. However, the symptoms may still be more severe on one side than on the other.
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From Diagnosis On: My First Days With Parkinsons
A Parkinsons diagnosis can bring many different emotions denial, anger, sadness, frustration. Its important to know that no matter what emotions you feel, youre not alone. Listen as experts people with Parkinsons and their loved ones discuss how theyve navigated emotions in the early years with Parkinsons. This podcast episode offers personal reflections on steps people can take toward acceptance and real-world advice for those recently diagnosed and beyond.
If youd rather listen on the go, or through any podcast app on your smartphone or tablet. If you enjoyed what you heard, share it with a friend or leave a review on iTunes. It helps listeners like you find and support our mission.
Host and person with Parkinson’s Larry Gifford leads a discussion with expert panelists:
- Barry Grey, nonfiction writer, TV producer and book editor diagnosed with Parkinsons in 2021 at age 65
- John Lipp, Parkinsons advocate, writer and nonprofit executive diagnosed with Parkinsons in 2015 at age 49
- Tim Hague Sr., registered nurse, founder of U-Turn Parkinsons, co-founder of PD Avengers diagnosed with Parkinsons in 2011 at age 46
- Sheryl Hague: Tim Hague Sr.s wife and care partner
In this podcast, the host also highlights six tips for your first year with Parkinsons . Learn about those tips on our website.
Breakthroughs In Treatments And Therapies
Current therapies for Parkinsons often involve replacing dopamine. Dopamine replacement therapy was a dramatic breakthrough in the late 1960s and early 1970s. Since then, researchers have been looking for ways to reduce the side effects inherent in this type of treatment. Dr. Stern is enthusiastic about these newer forms of dopamine therapy, including infusions and long-acting oral formulations, which more closely mimic how the body naturally processes dopamine.
He also points to research that is helping us better understand the beneficial effects of non-drug treatments such as regular exercise and dietary changes. There are some studies that have shown that a regular exercise program and things like the Mediterranean Diet may actually reduce the incidence and severity of Parkinsons disease, says Dr. Stern.
Dr. Stern also encouraged people with Parkinsons to talk to their doctor about all symptoms they are experiencingnot just the ones they think are related to the disease. For many people, the non-motor symptoms of Parkinsonswhich can include anxiety, depression, and sleep issuescan be a greater source of disability than the typical motor symptoms. Finding ways to deal with these symptoms is every bit as important to addressing a persons overall well-being.
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How Could Stem Cells Help People With Parkinson’s
Stem cells are the parent cells of all tissues in the body. This means they can turn into any type of cell. The hope is that they will eventually be able to make these cells into specific types of cells, like dopamine-producing neurons, that can be used to treat Parkinson’s disease. However, there are concerns that patients may have the same risk of increased involuntary movements as those who undergo fetal cell transplantation. And, like fetal cell transplantation, stem cell therapy is surrounded by moral and ethical controversy.
What The Research Data Tells Us
Over the past eight months, physicians and scientists with expertise in PD have gathered their preliminary data on the experience of people with PD with COVID-19. These findings have been published in journals for others to learn from. This type of work is not unique to PD of course. Physicians are collating the data on how COVID-19 affects different people with the entire array of human conditions.
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Latest Research On Covid
UPDATE: This post has been updated with the latest information available.We will continue to keep this post up-to-date as new information develops.
As citizens of the world, we all continue to grapple with the COVID-19 pandemic. And as members of the Parkinsons disease community, we continue to have specific concerns about COVID-19 and how it relates to PD. There is so much information out there, some of it misinformation, so it is important to rely on credible, trusted sources. In this post, I will cover the latest information that investigates the relationship between PD and COVID-19.
The Motor Network In Parkinsons Disease And Dystonia: Mechanisms Of Therapy
open to eligible people ages 21-75
This is an exploratory pilot study to identify neural correlates of specific motor signs in Parkinsons disease and dystonia, using a novel totally implanted neural interface that senses brain activity as well as delivering therapeutic stimulation. Parkinsons disease and isolated dystonia patients will be implanted unilaterally or bilaterally with a totally internalized bidirectional neural interface, Medtronic Summit RC+S. This study includes three populations: ten PD patients undergoing deep brain stimulation in the subthalamic nucleus , ten PD patients with a globus pallidus target and five dystonia patients. All groups will test a variety of strategies for feedback-controlled deep brain stimulation, and all patients will undergo a blinded, small pilot clinical trial of closed-loop stimulation for thirty days.
San Francisco, California
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What New Treatments Are Being Developed
Thanks to the progress weve already made, new treatments are being tested in clinical trials that have the potential to slow, stop or even reverse Parkinsons.
These include:
- stem cell therapies, which aim to use healthy, living cells to replace or repair the damage in the brains of people with Parkinsons
- gene therapies, which use the power of genetics to reprogramme cells and change their behaviour to help them stay healthy and work better for longer
- growth factors , which are naturally occurring molecules that support the growth, development and survival of brain cells.
And were developing treatments that aim to improve life with the condition, including new drugs that can reduce dyskinesia.
Healthy Eating With Pd
Eating a whole food, plant-based diet, often called a Mediterranean diet, can help you live well with PD. Eat what you need to eat to be happy but also eat more of the food that is good for your health.
If you have Parkinsons, every healthy lifestyle change can help. Choosing to eat well also leads to a feeling of empowerment that helps you in your daily life with PD. While it can be challenging to eat better, most people make minor diet changes gradually that become major changes over time. Always consult your physician before making major changes.
To learn more about nutrition and Parkinsons, visit Parkinson.org/nutrition or read more about the Mediterranean diet.
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Parkinsons Foundation Seeks To Add To Global Care Network In Us
To help expand patient access to treatments and other services, the Parkinsons Foundation is inviting U.S. medical centers that provide outstanding Parkinsons disease clinical care and resources to apply for membership in its Global Care Network. The network comprises Parkinsons Foundation Centers of Excellence as well as