### Parkinson's Disease Overview
**Parkinson's disease** is a progressive neurological disorder that primarily affects movement. It occurs when certain nerve cells (neurons) in a part of the brain called the substantia nigra break down or die. These neurons produce dopamine, a chemical messenger crucial for transmitting signals in the brain that coordinate smooth and balanced muscle movements. As these neurons deteriorate, dopamine levels decrease, leading to the movement symptoms characteristic of Parkinson's disease.
### Causes
The exact cause of Parkinson's disease is unknown, but several factors are believed to contribute:
1. **Genetic Factors:** Mutations in certain genes have been linked to Parkinson's, but they account for a small percentage of cases. A family history of Parkinson's increases the risk.
2. **Environmental Factors:** Exposure to certain toxins, such as pesticides and herbicides, has been associated with an increased risk of developing Parkinson's.
3. **Age:** The risk of Parkinson's increases with age, most commonly affecting people over 60.
4. **Gender:** Men are more likely to develop Parkinson's than women.
### Early Signs and Symptoms
The early symptoms of Parkinson's disease are often subtle and may be mistaken for normal aging. Common early signs include:
1. **Tremor:** A slight shaking or tremor, often beginning in a hand or fingers.
2. **Bradykinesia:** Slowness of movement, making simple tasks more difficult and time-consuming.
3. **Rigid Muscles:** Muscle stiffness that can occur in any part of the body and limit range of motion.
4. **Postural Instability:** Problems with balance and coordination, leading to a stooped posture or difficulty standing upright.
5. **Micrographia:** Handwriting becomes small and cramped.
6. **Facial Masking:** A decrease in facial expressions, sometimes referred to as a "masked face."
### Progression Over Time
Parkinson's disease progresses gradually, and symptoms typically worsen over time. The progression can be categorized into five stages:
1. **Stage 1:** Mild symptoms that do not interfere with daily activities. Tremors or other movement symptoms may be present on one side of the body.
2. **Stage 2:** Symptoms worsen and affect both sides of the body, but daily tasks can still be completed. Walking and posture may begin to be affected.
3. **Stage 3:** Significant slowing of movement and increased risk of falls. Daily activities become more difficult, but individuals can still live independently.
4. **Stage 4:** Severe symptoms, requiring assistance with most daily activities. The ability to live independently is greatly compromised.
5. **Stage 5:** The most advanced stage, characterized by severe disability. Individuals may be bedridden or in a wheelchair and need full-time care.
### Diagnosis of Parkinson's Disease
**Diagnosis** is primarily based on medical history, a review of symptoms, and a neurological and physical examination. There is no specific test for Parkinson's, so the diagnosis is often made by a specialist, such as a neurologist, based on the presence of characteristic signs and symptoms.
### Tests and Procedures for Diagnosis
To confirm a diagnosis, the following tests and procedures may be used:
1. **Neurological Examination:** The doctor will assess motor skills, muscle tone, reflexes, and coordination.
2. **DaTscan:** An imaging test that allows doctors to visualize dopamine transporters in the brain. This can help differentiate Parkinson's disease from other conditions with similar symptoms.
3. **MRI or CT Scan:** These imaging tests are used to rule out other conditions that may cause similar symptoms, such as a stroke or brain tumor.
4. **Blood Tests:** These may be performed to exclude other disorders that may be causing the symptoms.
5. **Response to Parkinson's Medications:** A significant improvement in symptoms with the use of medications that increase dopamine levels can support the diagnosis of Parkinson's.
Diagnosing Parkinson's disease can be challenging, especially in its early stages, so ongoing monitoring and follow-up are essential to confirm the diagnosis and track the progression of the disease.
Some common attitude shifts that people with Parkinson's might experience include:
Attitude shifting in Parkinson's disease refers to changes in a person's outlook, mood, or behavior that can occur as part of the disease's progression or as a side effect of treatment. Parkinson's is primarily known for its motor symptoms, like tremors and rigidity, but it also affects the brain's chemistry, leading to cognitive and emotional changes.
1. **Depression and Anxiety**: Due to the changes in brain chemistry, people with Parkinson's often experience mood disorders. Depression and anxiety are particularly common and can significantly affect one's attitude and outlook on life.
2. **Apathy**: A lack of motivation or indifference, known as apathy, can occur in Parkinson's. This can make it difficult for individuals to engage in activities they once enjoyed or to maintain a positive attitude.
3. **Impulsivity**: Some Parkinson's treatments, especially those involving dopamine agonists, can lead to impulse control disorders. This can result in behaviors like gambling, hypersexuality, or binge eating, which can dramatically shift a person's attitude and behavior.
4. **Cognitive Changes**: As Parkinson's progresses, some people may experience changes in their thinking and memory, which can alter their attitude. For example, they might become more rigid in their thinking, struggle with decisin, which can also affect their overall attitude.
Support from healthcare professionals, counseling, medication adjustments, and a strong support network can help manage these changes and maintain a positive quality of life.
Some common attitude shifts that people with Parkinson's might experience include:
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Here Here are some tips for dealing with PSP on a daily basis
1. Medical Management
Medication- Consult with your neurologist about medications that might help manage symptoms, such as those to address stiffness, mood disorders, or other specific issues.
Regular Check-Ups: Maintain regular appointments with your healthcare team to monitor the progression of the disease and adjust treatment plans as necessary.
2. Physical Therapy: Work with a physical therapist to improve balance, mobility, and strength. They can also teach you exercises to maintain flexibility and reduce the risk of falls.
Occupational Therapy: An occupational therapist can help you with strategies to manage daily activities, suggest adaptive equipment, and modify your home environment to make it safer and more accessible.
3. Speech and Swallowing Therapy
Speech Therapy: Speech therapists can assist with communication difficulties by teaching you techniques to improve speech clarity or explore alternative communication methods if necessary.
Swallowing Therapy: They can also help with dysphagia (difficulty swallowing) by recommending exercises and dietary modifications to reduce the risk of choking and aspiration.
4. Assistive Devices and Home Modifications
Mobility Aids: Use canes, walkers, or wheelchairs to enhance mobility and prevent falls.
Home Safety: Make modifications to your home, such as installing grab bars, using non-slip mats, and ensuring good lighting to create a safer living environment.
5. Nutritional Management
Dietary Adjustments: Consult with a dietitian to ensure you are getting adequate nutrition, especially if swallowing becomes difficult. They can recommend food textures and consistencies that are easier to swallow.
Hydration: Maintain proper hydration, which is crucial for overall health and can help with swallowing difficulties.
6. Emotional and Mental Health Support
Counseling: Seek psychological counseling or support groups for emotional support. Coping with a chronic illness can be challenging, and having someone to talk to can make a significant difference.
Support Groups: Join support groups for PSP patients and their families. Sharing experiences and advice with others who understand can provide comfort and practical tips.
7. Daily Routine and Activity Management
Structured Routine: Establish a structured daily routine to provide a sense of normalcy and control.
Pacing Activities: Pace yourself and rest frequently to avoid fatigue. Break tasks into smaller, manageable steps.
Engagement in Activities: Engage in activities that you enjoy and can manage, such as reading, listening to music, or gentle gardening.
8. Caregiver Support
Training and Education: Educate caregivers about PSP and train them in assisting with daily activities, mobility, and emergency procedures.
Respite Care: Arrange for respite care to give primary caregivers a break and prevent burnout.
9. Technological Assistance
Communication Aids: Utilize technology, such as speech-generating devices or communication apps, to help with communication if speech becomes difficult.
Health Monitoring: Use health monitoring devices to track symptoms and manage medication schedules.
10. Legal and Financial Planning
Advance Directives: Prepare advance directives to outline your wishes for medical care.
Financial Planning: Consult with a financial advisor to manage the costs associated with long-term care and to plan for the future.
Managing PSP requires a multidisciplinary approach and the support of healthcare professionals, family, and friends. While there is no cure for PSP, these strategies can help improve daily living and enhance quality of life.
Promising Targets Discovered for Rare Brain Disorder PSP
Summary: Researchers have identified new therapeutic targets for progressive supranuclear palsy (PSP), an incurable brain disorder with symptoms mimicking Parkinson’s and dementia.
The study focused on RNA sequencing from brain samples of over 400 individuals. By analyzing almost 5,000 genes linked with PSP, the team prioritized 11 high-confidence genes.
Reducing levels of DDR2, KANK2, and STOM showed significant promise in reversing the disease.
Key Facts:
- Progressive supranuclear palsy (PSP) is an incurable brain disorder that leads to rapid decline and death.
- Using RNA sequencing from more than 400 brain samples, researchers identified nearly 5,000 genes associated with PSP.
- Among the high-confidence genes, reducing levels of DDR2, KANK2, and STOM presented potential for therapeutic development.
Source: Mayo Clinic
There is no cure for progressive supranuclear palsy (PSP), a brain disorder marked by walking and balance difficulties. Its symptoms also mimic Parkinson’s disease and dementia. The condition leads to rapid, progressive decline and death.
In a new paper published in Nature Communications, Mayo researchers and collaborators outline new therapeutic targets that may lead to potential future treatments for PSP, as well as Alzheimer’s disease and related disorders.
The next steps in this research are to work on the synthesis of small nucleic acid molecules that can regulate the target genes identified in this study. Credit: Neuroscience NewsPeople with PSP usually are diagnosed in their late 60s and 70s. While the cause isn’t known, researchers have found that the deteriorating brain cells of people with PSP have excess amounts of a protein called tau. Clumps of tau are also found in people with other neurodegenerative disorders, such as Alzheimer’s disease.
In this study, the researchers zeroed in on RNA, the carrier of genetic information in all living cells.
They integrated brain RNA data from two large, independent human study groups, including donor samples from patients with PSP from the Mayo Clinic Brain Bank. They performed RNA sequencing, which allowed them to discover which genes in certain brain cells were abnormally high or low in patients with PSP.
Each study group contained brain samples from people who had died from PSP, as well as a control group of brain samples from people who did not die from a neurodegenerative disorder. The researchers used samples from more than 400 people overall.
After performing the RNA sequencing, the researchers used a computational model to systematically identify nearly 5,000 genes involved in PSP in relevant brain cells. They then compared their findings to an analysis performed in a preclinical model that mimics the brain pathology seen in PSP.
In the end, the researchers “ranked,” or prioritized, 11 high-confidence genes that are unusually elevated in human PSP brains and this model.
Finally, the investigators manipulated these target genes in an experimental fruit fly model. They wanted to determine whether reducing the levels of these abnormally elevated genes could correct the degeneration in the model.
Among the 11 high-confidence genes, researchers found that reducing the levels of DDR2, KANK2 and STOM showed the most promise in reversing disease and as leading targets for therapeutic development.
“This research enhances our understanding of progressive supranuclear palsy and other related incurable neurological disorders,” says the study’s senior author, Nilüfer Ertekin-Taner, M.D., Ph.D., a Mayo Clinic neurologist, neuroscientist and chair of the Department of Neuroscience.
“Moving forward, we can target these specific genes or others that are biologically related to them to develop a potential treatment for this untreatable disease.”
The team also built a web application to enable data-sharing among the wider research community.
“This project highlights the power of multiomics data,” says Yuhao (Harry) Min, a Mayo Clinic Graduate School of Biomedical Sciences predoctoral student in the Clinical and Translational Science track and first author of the paper.
“Using these datasets, we were able to tease apart the complex molecular changes that took place in patients with PSP, which is important to understand to find a cure for this disorder.
“We also shared our datasets with the scientific community to enable collaborative efforts, with the goal of finding a treatment for patients. Because PSP shares similar biology as other neurological disorders such as Alzheimer’s disease, we hope our findings might also benefit drug discovery efforts in other neurological disorders.”
The next steps in this research are to work on the synthesis of small nucleic acid molecules that can regulate the target genes identified in this study. The researchers hope to assess the safety and efficacy of those molecules in cell and animal models, with the long-term goal of beginning clinical trials in PSP patients.
About this PSP and neurology news
Author: Lynda De Widt
Source: Mayo Clinic
Contact: Lynda De Widt – Mayo Clinic
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Cross species systems biology discovers glial DDR2, STOM, and KANK2 as therapeutic targets in progressive supranuclear palsy” by Nilüfer Ertekin-Taner et al. Nature Communication
Abstract
Cross species systems biology discovers glial DDR2, STOM, and KANK2 as therapeutic targets in progressive supranuclear palsy
Progressive supranuclear palsy (PSP) is a neurodegenerative parkinsonian disorder characterized by cell-type-specific tau lesions in neurons and glia. Prior work uncovered transcriptome changes in human PSP brains, although their cell-specificity is unknown. Further, systematic data integration and experimental validation platforms to prioritize brain transcriptional perturbations as therapeutic targets in PSP are currently lacking.
In this study, we combine bulk tissue (n = 408) and single nucleus RNAseq (n = 34) data from PSP and control brains with transcriptome data from a mouse tauopathy and experimental validations in Drosophila tau models for systematic discovery of high-confidence expression changes in PSP with therapeutic potential. We discover, replicate, and annotate thousands of differentially expressed genes in PSP, many of which reside in glia-enriched co-expression modules and cells.
We prioritize DDR2, STOM, and KANK2 as promising therapeutic targets in PSP with striking cross-species validations. We share our findings and data via our interactive application tool PSP RNAseq Atlas (https://rtools.mayo.edu/PSP_RNAseq_Atlas/).
Our findings reveal robust glial transcriptome changes in PSP, provide a cross-species systems biology approach, and a tool for therapeutic target discoveries in PSP with potential application in other neurodegenerative disea
PROGRESSIVE SUPRANUCLEAR PALSY NEWS AND RESEARCH
C-Path announces formation of new task force to foster drug development for Progressive Supranuclear Palsy
Critical Path Institute (C-Path) today announced the formation of a new task force under its Rare Disease Cures Accelerator-Data and Analytics Platform, dedicated to advancing therapeutic development for Progressive Supranuclear Palsy.
UVA Alzheimer's study pinpoints how tau protein damages brain cells
University of Virginia Alzheimer's researchers have discovered how harmful tau proteins damage the essential operating instructions for our brain cells, a finding which could lead to new treatments.
Redefining the battle against Alzheimer's with tau-focused treatments
Researchers explore the potential of tau-targeting therapies in treating Alzheimer's disease, focusing on immunotherapies and strategies to improve their efficacy. The study dives into the complex biology of tau proteins, their modifications, and how they can be targeted to halt the progression of Alzheimer's.
Wearable devices and machine learning revolutionize Parkinson's disease monitoring
The quantitative progression of motor symptoms of Parkinson's disease (PD) over time using wearable sensor data.
Developer launches long-awaited study of light device for Parkinson’s
PhotoPharmics overcomes funding, pandemic challenges to test treatment
by Marisa Wexler, MS | March 28, 2024
After years of delays, medical device company Photopharmics has started a pivotal clinical trial to test its Celeste device, a noninvasive treatment tool that aims to use light to manage the symptoms of Parkinson’s disease.
The long-awaited trial has been in the works since 2020, shortly after the light-based therapy was granted breakthrough device designation by the U.S. Food and Drug Administration (FDA).
“After overcoming funding challenges and delays caused by the global pandemic, we are thrilled to launch this trial, which holds immense promise for those affected by Parkinson’s disease,” Kent Savage, president and CEO of Photopharmics, said in a company press release.
The study is being run as a collaboration between Photopharmics and the Center for Health and Technology at the University of Rochester Medical Center (URMC), in New York. Additional information, including a form patients can use to determine if they’re eligible to participate in the study, is available at the trial’s website, lightforpd.com.
How a red light and profanity have helped us in life with Parkinson’s
Telemedicine trial approach will assess light device from patients’ homes
The Celeste device was developed based on the finding that Parkinson’s frequently causes damage to cells in the retina, the part of the eye that senses light. The research showed that patients often experience abnormalities in circadian rhythms — the day-by-day biological cycles that help control bodily processes like hunger and sleep.
The device, which is noninvasive, uses light-based therapy, called phototherapy, to activate specific receptors in the eye that help regulate circadian rhythms. In doing so, the light device aims to help ease Parkinson’s symptoms that are associated with circadian rhythm abnormalities, such as sleep problems, fatigue, and depression.
Dan Adams, Photopharmics’ chief science officer, said the device “demonstrated remarkable improvements in both quality of life and non-motor symptoms for [Parkinson’s] patients” in early clinical studies.
Adams added that Celeste promises to be “a new horizon in [Parkinson’s] treatment.”
According to Adams, a pivotal trial for a medical device is similar to a Phase 3 clinical trial for a medication — it’s a large study designed to test the effectiveness of the treatment. He said that Photopharmics has already presented the trial’s design to the FDA, which gave it a “favorable review.”
The trial’s design was to be shared with scientists and medical professionals last year at the World Parkinson Congress, which the company hoped would allow for collaboration with researchers
Understanding the Connection Between Dementia Risk and Parkinson's Disease: Insights from Drug Development and Genetic Research
As our understanding of the complex relationship between Parkinson's disease and dementia risk deepens, so too does the potential for breakthroughs in treatment. With ongoing research and innovation, the future looks promising for individuals living with Parkinson's disease, offering hope for improved quality of life and better management of cognitive decline.
### Understanding the Connection Between Dementia Risk and Parkinson's Disease: Insights from Drug Development and Genetic Research
Parkinson's disease (PD) is a progressive neurodegenerative disorder primarily known for its motor symptoms, such as tremors, stiffness, and bradykinesia. However, an often-overlooked aspect of PD is the heightened risk of dementia associated with the condition. As the disease progresses, cognitive decline becomes increasingly prominent, leading to Parkinson's disease dementia (PDD). This connection between Parkinson's and dementia risk has become a critical focus of both genetic research and drug development efforts.
The Role of Genetic Research in Understanding Dementia Risk
Recent advancements in genetic research have provided valuable insights into the relationship between Parkinson's disease and dementia. Specific genetic mutations, such as those in the LRRK2 and GBA genes, have been identified as significant contributors to the risk of developing Parkinson's and its associated cognitive decline. Understanding these genetic factors is essential for predicting dementia risk in Parkinson's patients and for developing targeted interventions.
Genetic research has also shed light on the broader mechanisms underlying neurodegeneration. By studying the genetic links between Parkinson's and other neurodegenerative diseases like Alzheimer's, researchers are uncovering common pathways that contribute to cognitive decline. This knowledge is crucial for identifying new therapeutic targets that could help prevent or slow the progression of dementia in Parkinson's patients.
Drug Development: A Focus on Neuroprotection
Given the close link between Parkinson's disease and dementia, there is a growing emphasis on developing drugs that offer neuroprotection. Neuroprotective drugs aim to preserve brain function and prevent the loss of neurons that contribute to both motor and cognitive symptoms. These drugs target various mechanisms, such as reducing oxidative stress, modulating inflammation, and enhancing mitochondrial function, all of which are implicated in neurodegeneration.
One promising avenue in drug development is the use of disease-modifying therapies that target the underlying causes of Parkinson's. For instance, therapies that reduce the accumulation of alpha-synuclein, a protein that forms toxic aggregates in the brains of Parkinson's patients, hold potential for not only alleviating motor symptoms but also reducing dementia risk.
The Future of Parkinson's Disease Research and Treatment
The intersection of genetic research, drug development, and neuroprotection is paving the way for a future where Parkinson's disease and its associated dementia risk can be more effectively managed. By continuing to explore the genetic underpinnings of the disease and developing drugs that target the root causes of neurodegeneration, researchers are hopeful that they can delay or even prevent the onset of dementia in Parkinson's patients.