Sidebar: Morris K Udall Centers Of Excellence For Parkinson’s Disease Research
The Morris K. Udall Parkinsons Disease Research Act of 1997 authorized the NIH to greatly accelerate and expand PD research efforts by launching the NINDS Udall Centers of Excellence, a network of research centers that provide a collaborative, interdisciplinary framework for PD research. Udall Center investigators, along with many other researchers funded by the NIH, have made substantial progress in understanding PD, including identifying disease-associated genes investigating the neurobiological mechanisms that contribute to PD, developing and improving PD research models, and discovering and testing potential therapeutic targets for developing novel treatment strategies.
The Udall Centers continue to conduct critical basic, translational, and clinical research on PD including: 1) identifying and characterizing candidate and disease-associated genes, 2) examining neurobiological mechanisms underlying the disease, and 3) developing and testing potential therapies. As part of the program, Udall Center investigators work with local communities of patients and caregivers to identify the challenges of living with PD and to translate scientific discoveries into patient care. The Centers also train the next generation of physicians and scientists who will advance our knowledge of and treatments for PD. See the full list of Udall Centers.
How Do I Take Care Of Myself
If you have Parkinsons disease, the best thing you can do is follow the guidance of your healthcare provider on how to take care of yourself.
- Take your medication as prescribed. Taking your medications can make a huge difference in the symptoms of Parkinson’s disease. You should take your medications as prescribed and talk to your provider if you notice side effects or start to feel like your medications aren’t as effective.
- See your provider as recommended. Your healthcare provider will set up a schedule for you to see them. These visits are especially important to help with managing your conditions and finding the right medications and dosages.
- Dont ignore or avoid symptoms. Parkinsons disease can cause a wide range of symptoms, many of which are treatable by treating the condition or the symptoms themselves. Treatment can make a major difference in keeping symptoms from having worse effects.
Diagnosis Of Parkinsons Disease
There are currently no blood or laboratory tests to diagnose non-genetic cases of Parkinsons. Doctors usually diagnose the disease by taking a persons medical history and performing a neurological examination. If symptoms improve after starting to take medication, its another indicator that the person has Parkinsons.
A number of disorders can cause symptoms similar to those of Parkinsons disease. People with Parkinsons-like symptoms that result from other causes, such as multiple system atrophy and dementia with Lewy bodies, are sometimes said to have parkinsonism. While these disorders initially may be misdiagnosed as Parkinsons, certain medical tests, as well as response to drug treatment, may help to better evaluate the cause. Many other diseases have similar features but require different treatments, so it is important to get an accurate diagnosis as soon as possible.
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The Results Of The Phase 2 Placebo
During post market trading hours on December 5, 2022, BioVie has announced that its Phase 2 trial in Parkinson’s disease has met both of its objectives.
Patients treated with the combination of NE3107 and levodopa saw improvements in their UPDRS Part III score that is 3+ points superior to patients treated with levodopa alone.
Phase 2 Parkinson’s study results slide 1
Patients under 70 years of age treated with NE3107/levodopa experienced roughly 6 points superiority compared to those treated with levodopa alone, suggesting that younger patients with less advanced disease progression may experience greater impact from treatment with NE3107. This is consistent with the Phase 2 Alzheimer’s data, and with many other studies, where effects were seen most strongly in patients that had less progressed disease. As a reminder, Parkinson’s sets in when about 80% of the dopamine-producing cells are already gone. Equally, the first brain changes in Alzheimer’s are detected 20 years before symptoms onset.
After 28 days of treatment, 63.6% of patients treated with levodopa alone experienced > 30% improvement from Day 0 at the two-hour mark compared to 80% for NE3107+levodopa-treated patients and 88.9% of NE3107+levodopa patients under 70 years old. This pattern is also observed for other time periods.
Phase 2 trial in Parkinson’s – slide 2
The Hoehn And Yahr Scale: Uses And Setbacks
To quantify disease progression, there is a commonly referenced staging scale. However, the staging of Parkinsons disease does have significant drawbacks. The Hoehn and Yahr scale was developed by Drs. Margaret Hoehn and Melvin Yahr in 1967:
- Stage I: Symptoms involve one side of the body
- Stage 2: Symptoms involve both sides of the body, or the midline
- Stage 3: Symptoms involve both sides of the body, with impairment of balance
- Stage 4: Symptoms have advanced to the point that although the person can stand and walk without the help of another person, he/she has significant disability. People in this stage typically need at least some help to perform their activities of daily living, or self-care activities such as eating, bathing, dressing, and toileting.
- Stage 5: The person cannot stand or walk without the help of another person
Hoehn and Yahr Scale Doesnt Factor in Progression of Non-motor Symptoms
The Hoehn and Yahr scale focuses solely on the progression of motor symptoms and does not consider the psychiatric, cognitive, and autonomic non-motor symptoms that often cause more disability than motor symptoms as PD advances. This is a major limitation of the Hoehn and Yahr scale.
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Stages Of Parkinsons Disease
The progression of Parkinsons disease is commonly divided into five stages of symptoms that worsen over time. However, while some people with Parkinsons may become severely disabled, others may not.
Not everyone experiences all the symptoms of Parkinsons, and symptoms are not necessarily experienced in the same order, says Dr. Maurer.
The stages of Parkinsons are generally defined as follows.
Ne3107 Seen To Reversing The Biological Clock In Alzheimer’s Patients
In pre-market trading on December 6, 2022, BioVie reported something rather mind-blowing, the more I am looking into it. It had announced that NE3107 appears to have reversed the biological clock of its Alzheimer’s patients on trial by 3.3 years on average after 3 months of treatment.
BioVie had sent patients’ blood samples to Steve Horvath, a world-renowned expert in the field of aging and epigenetics. On the basis of the study of DNA-methylation, Prof. Horvathdesignsepigenetic biological clocks, which are essentially algorithms designed to find out someone’s biological age. In 2019, a small studycombining a growth hormone with two anti-diabetes drugs. Results made world news headlines and were in Nature, as the study had been able to reverse patients’ biological clocks by 2.5 years over the course of one year of treatment. The study was considered to basically turn back time. Interestingly also, in 2021, a study came out showing that excellent responders to anti-TNF therapy in psoriasis had better SkinBloodAge compared to partial responders.
In 2022, we now have a study that seemingly largely surpasses the above findings of 2019. Treatment with NE3107 for three months showed a reduction of 3.3 years on the Horvath DNA methylation SkinBlood clock. Furthermore, not less than 19 out of the 22 patients experienced a reduction in the SkinBlood clock score.
DNA Methylation Age Skin Blood Clock Slide 1
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What Are The Five Stages Of Parkinsons Disease
Researchers may disagree on the number of stages of Parkinsons disease . However, they all agree the disease is a progressive disease with symptoms that usually occur in one stage may overlap or occur in another stage. The stage increase in number value for all stage naming systems reflect the increasing severity of the disease. The five stages used by the Parkinsons Foundation are:
- Stage 1: mild symptoms do not interfere with daily activities and occur on one side of the body.
- Stage 2: Symptoms worsen with walking problems and both sides of the body affected.
- Stage 3: Main symptoms worsen with loss of balance and slowness of movement.
- Stage 4: Severity of symptoms require help usually person cannot live alone.
- Stage 5:Caregiver needed for all activities patient may not be able to stand or walk and may be bedridden and may also experience hallucinations and delusions.
A neurologist who specializes in movement disorders will be able to make the most accurate diagnosis. An initial assessment is made based on medical history, a neurological exam, and the symptoms present. For the medical history, it is important to know whether other family members have Parkinsons disease, what types of medication have been or are being taken, and whether there was exposure to toxins or repeated head trauma previously. A neurological exam may include an evaluation of coordination, walking, and fine motor tasks involving the hands.
The diagnosis of Parkinsons disease is more likely if:
Sensitivity Of Predictions To Feature Removal
To further validate the relative importance of predictive features, we removed genetic, neuroimaging, survey-based, and physician exam-based predictive features and evaluated the impact on 12-moth MDS-UPDRS total meta-prediction accuracy . Removing genetic predictors led to the greatest loss in accuracy both when tested on PDBP ROC AUC 0.74 vs 0.66, PR AUC 0.73 vs 0.66, and when performing train-test splitting on PPMI ROC AUC 0.77 vs 0.66, PR AUC 0.76 vs 0.68 . Removing physician exam-based predictive features led to the next greatest loss in accuracy when tested on PDBP ROC AUC 0.74 vs 0.69, PR AUC 0.73 vs 0.71, and when performing train-test splitting on PPMI ROC AUC 0.77 vs 0.67, PR AUC 0.76 vs 0.71. Removing survey-based predictive features led to the third-most greatest loss in accuracy when tested on PDBP ROC AUC 0.74 vs 0.72, PR AUC 0.73 vs 0.72, and when performing train-test splitting on PPMI ROC AUC 0.77 vs 0.72, PR AUC 0.76 vs 0.72. And removing neuroimaging-based predictive features led to the least reduction in accuracy, only testable when train-test splitting PPMI ROC AUC 0.77 vs 0.73, PR AUC 0.76 vs 0.73 . Full confusion matrices from these results are presented in Supplemental Table . Additional accuracy metrics are provided in Supplemental Table .
Table 4 Feature component accuracy of 12-month MDS-UPDRS total meta-prediction.
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Parkinsons Disease For Primary Care With Dr Albert Hung
December 5, 2022 By Matthew Watto, MD
Master the ins-and-outs of Parkinsons Disease! Were joined by Dr. Albert Hung, who teaches us pearls for the initial history and physical exam in a patient with undiagnosed Parkinsons, a framework for management of early and advanced motor symptoms, tips for treating autonomic symptoms and cognitive / psychiatric features, and more.
Claim free CME for this episode at curbsiders.vcuhealth.org!
- Producer, Writer, Show Notes, and Infographic: Malini Gandhi
- Cover Art: Kate Grant
- Hosts: Matthew Watto MD, FACP Paul Williams MD, FACP
- Reviewer: Emi Okamoto MD
- Showrunner: Matthew Watto MD, FACP Paul Williams MD, FACP
- Technical Production: PodPaste
Visit betterhelp.com/curb to save 10% off your first month.
What Does This Mean For Me
Parkinsons is a complex disease that affects many aspects of life. It is hard to rate the severity of PD using scales since the condition looks differently for everyone living with it.2
Also, people may feel differently about different symptoms. Some people living with PD might feel strongly about problems walking while others might feel strongly about difficulty speaking.2
The stage of your disease also cannot predict your lifespan or how it will continue to progress. The different staging systems were created to help experts and those living with the disease to have a clear way to discuss symptoms. It also helps researchers understand which treatments are helpful for which symptoms.2
If you have more questions about your PD or if you need more support, reach out to your healthcare team.
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A Way To Slow Parkinsons
Blocking Specific Form of a Brain Chemical Could Slow Brain Cell Loss, Researchers Find
In the animal model, the researchers found they could slow the death of affected brain cells by about half by blocking the chemical, called soluble TNF.
The finding offers a target for new drugs that could slow the progression of the debilitating and deadly disease. And it may apply to Alzheimers diseaseAlzheimers disease as well, suggest University of Texas Southwestern Medical Center researchers Melissa K. McCoy, MalÃº G. Tansey, PhD, and colleagues.
The researchers report their study in the Sept. 13 issue of The Journal of Neuroscience.
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Data Reported Prior To Ctad 2022
BioVie had on announced that, in an open label Phase 2 study, NE3107 treatment saw 82% of 17 patients with MMSE > =20 experience a 2.6 point decrease in ADAS-Cog12 . A similar pattern of improvement was observed using the QDRS, a rating scale to assess cognition and function, scored from 0 to 3 , where 71% of 17 MCI/mild AD patients improved with a mean change of -1.35 . NE3107 was also associated with improvements in the patients’ daily abilities and overall sense of well-being as reported by the clinical, families and patients on the basis of the Global Rating of Change rating scale, with p-values ranging in between p< 0.0001 and p< 0.05.
NE3107 treatment saw a significant correlation between reductions in the inflammatory marker TNFa and improvements in cognition.
That initial reporting further saw reduced CSF p-tau levels, improvements in blood flow, a lower ratio of p-tau to AÎ²42predictive of amyloid burden, reduction in hyperactivation of the hippocampus and increased levels of glutathione as a master regulator of oxidative stress.
No drug related adverse events have been reported.
Many of these initial findings have been covered more extensively in my earlier coverage, so I will limit it here to some fundamental slides.
NE3107 Phase 2 Adas-Cog12 data
Cognitive Correlations With TNF Reduction
BioVie reported quite some additional information during the Alzheimer’s conference, which I will try to summarize below. The full data can be found here.
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How Do I Know If I Have A Swallowing Problem
- I have recently lost weight without trying.
- I tend to avoid drinking liquids.
- I get the sensation of food being stuck in my throat.
- I tend to drool.
- I notice food collecting around my gum line.
- I tend to cough or choke before, during or after eating or drinking.
- I often have heartburn or a sore throat.
- I have trouble keeping food or liquid in my mouth.
*Please note that not all content is available in both languages. If you are interested in receiving Spanish communications, we recommend selecting both to stay best informed on the Foundations work and the latest in PD news.
Sidebar: Ninds Steps Up Pursuit Of Pd Biomarkers
In 2012, the NINDS dramatically accelerated efforts to identify biomarkers by establishing the Parkinsons Disease Biomarkers Program . This unprecedented program unites a range of stakeholders from basic and clinical researchers to healthcare professionals, the NINDS staff, information technology experts, and people living with PD and their families.
PDBP supports research and builds resources aimed at accelerating the discovery of biomarkers to ultimately slow the progression of PD. For example, the program has established a repository of biological specimens and a Data Management Resource system maintained by the NIH Center for Information Technology. The DMR allows researchers to access clinical, imaging, genetic, and biologic data, while a complementary PDBP-supported project develops statistical tools to analyze vast quantities of data so that patterns can be identified across these diverse sources of information.
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What To Expect In The Late Stages Of Parkinsons Disease
- Stage Four of Parkinsons Disease In stage four, PD has progressed to a severely disabling disease. Patients with stage four PD may be able to walk and stand unassisted, but they are noticeably incapacitated. Many use a walker to help them. At this stage, the patient is unable to live an independent life and needs assistance with some activities of daily living. The necessity for help with daily living defines this stage. If the patient is still able to live alone, it is still defined as Stage Three.
- Stage Five of Parkinsons Disease Stage five is the most advanced and is characterized by an inability to arise from a chair or get out of bed without help. They may have a tendency to fall when standing or turning, and they may freeze or stumble when walking. Around-the-clock assistance is required at this stage to reduce the risk of falling and help the patient with all daily activities. At stage five, the patient may also experience hallucinations or delusions.1,2
New Gene Therapy Trial To Explore Parkinsons Disease Treatment Option
MORGANTOWN, W.Va – The WVU Rockefeller Neuroscience Institute has announced the start of a clinical trial that evaluates the safety and efficacy of a new gene therapy in the treatment of Parkinsons disease.
While surgical implants used in deep brain stimulation can treat Parkinsons disease, gene therapy can be of particular benefit without the need for implants in the brain.
This new study is the next step from a previous sham-controlled study that showed promise in Parkinsons disease, Dr. Ali Rezai, executive chair of the WVU Rockefeller Neuroscience Institute, said. In this study, AAV-GAD gene therapy is delivered to the subthalamic nucleus, a key area with dysfunction in a brain with Parkinsons disease. Over time, the gene therapy is intended to help Parkinsons disease by making new brain connections and improving symptoms.
The first participant is a grandparent of 14 from West Virginia who was forced to retire because of the progression and severity of Parkinsons disease.
Medications had become less effective with worsening side effects.
They hope their participation in this study not only helps them find relief, but also leads to advances in treatment for others with Parkinsons.
I hope this gene therapy will help my Parkinsons and also help other people, the participant said.
For more information on the study, .
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