Important Points About The New Medications
With multiple new medications available for the treatment of PD, there is more hope than ever that Parkinsons symptoms can be successfully managed for many years. A few things to consider:
- For people whose symptoms are difficult to control, these new treatments are welcome additions to what was previously available and many people with PD have been using these new medications with significant benefit.
- On the other hand, many of the newly-approved medications have the same mechanisms of action as older medications so they are not breaking new ground in treating symptoms.
- In addition, for some people, the effect on symptoms may be mild or not substantial.
These caveats may mean that your physician has not suggested a medication change for you. It is also important to note that despite all the new medications, carbidopa/levodopa remains the most potent medication to treat the motor symptoms of PD.
If your doctor does choose to try one of the new options, there may be multiple paths that your doctor can take when contemplating a medication adjustment. Often trial and error is the only way to determine the best medication regimen for you, so you may need to practice some patience as you work together with your doctor to determine what works or doesnt work.
Advances In Parkinsons Disease Treatment
In honor of Parkinson’s Awareness Week, we are sharing the new and exciting discoveries in Parkinson’s disease treatment. Drs. Han-Lin Chiang and Yih-Ru Wu, leaders in Parkinson’s disease research, discuss some of the most promising advancements in the treatment of Parkinson’s disease.
It has been 200 years since Dr. James Parkinson published the An Essay On the Shaking Palsy describing the signs and symptoms of Parkinsons disease . Despite the fact that there are lots of treatment options out there to ameliorate the patients symptoms and to improve their quality of life, we still dont have any neuroprotective or disease-modifying therapy to slow down disease progression. But for patients with PD, the past few years have never been so hopeful in that new candidate therapies are being developed at a very fast pace.
New Developments In Parkinsons Disease Therapy
With this situation in mind, efforts over the last 20 years to develop new therapies for PD can be divided in two categories: improving symptomatic therapy of motor and non-motor symptoms and addressing potential causes of PD, with a focus on the protein alpha-synuclein, its chemistry, synthesis, aggregation, degradation, and interaction with other proteins in order to develop a disease modifying treatment.
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A New Era For Parkinsons Disease Treatment
March 2, 2022 | By
A non-invasive ultrasound treatment for Parkinsons disease that was tested in a pivotal trial led by University of Maryland School of Medicine researchers is now broadly available at the University of Maryland Medical Center .
Howard Eisenberg, MD, Dheeraj Gandhi, MD, MBBS, Paul Fishman, MD, PhD, Bert W. OMalley, MD.
The device, called Exablate Neuro, was approved in November by the U.S. Food and Drug Administration to treat advanced Parkinsons disease on one side of the brain. The approval was based on findings from the UMSOM clinical trial and effectively expands access to focused ultrasound beyond clinical trial participation.
Rapid Reversal of Symptoms
Focused ultrasound is an incisionless procedure, performed without the need for anesthesia or an in-patient stay in the hospital. Patients, who are fully alert, lie in a magnetic resonance imaging scanner, wearing a transducer helmet. Ultrasonic energy is targeted through the skull to the globus pallidus, a structure deep in the brain that helps control regular voluntary movement. MRI images provide doctors with a real-time temperature map of the area being treated. During the procedure, the patient is awake and providing feedback, which allows doctors to monitor the immediate effects of the tissue ablation and make adjustments as needed.
Patient: Focused Ultrasound Changed My Life
A New Era for Parkinsons Disease Treatment
What Are Mesenchymal Stem Cells
Stem cells are the body’s raw materials â cells from which all other cells with specialized functions are created. Mesenchymal stem cells are adult stem cells that have self-renewal, immunomodulatory, anti-inflammatory, signaling, and differentiation properties. Mesenchymal stem cells , self renewal capacity is characterized by their ability to divide and develop into multiple specialized cell types present in a specific tissue or organ.
Mesenchymal stem cells can be sourced from a variety of tissue including adipose tissue , bone marrow, umbilical cord tissue, blood, liver, dental pulp, and skin.
MSCs are widely used in the treatment of various diseases due to their self-renewable, differentiation, anti-inflammatory, and immunomodulatory properties. In-vitro and in-vivo studies have supported the understanding mechanisms, safety, and efficacy of MSC therapy in clinical applications.
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Treatments In Phase I Trials
As Parkinsons researchers work toward more precision medicines, they benefit from a wide range of therapeutic categories & tools to experiment with. Therapeutic categories refer to all the different categories of research focuses, like stem cells, antioxidants, and gene targeting, for example. With trials spanning more than 15 therapeutics categories in the Phase I pipeline, it has a broad range of focuses. Making discoveries in more therapeutic categories means we can one day provide access to personalized treatment solutions based on the specific causes and symptom presentation of each person living with Parkinsons.
There are 50 treatments in Phase I trials this year with about a 50/50 split between symptom-relieving products and disease-modifying treatments. Half of the treatments in Phase I are new discoveries as the result of pathfinding research. This is when researchers use insights from existing medications to seek out related products that warrant exploration.
Box 7 Neurorestorative Growth Factor Therapies For Parkinson’s Disease
Preclinical studies show that GDNF and neurturin are the two most promising growth factors considered for neurorestoration of the nigrostriatal dopaminergic system in animal models of PD.
Neither of these compounds was successful in alleviating parkinsonian motor signs when delivered in the striatum of PD patients.
The antiparkinsonian efficacy of both striatal and nigral delivery of neurturin is currently being tested in another clinical trial.
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The Parkinsons Disease Medication Pipeline
The pipeline for Parkinsons disease medications is extremely crowded these days, with multiple medications at various stages of research development. This is very exciting news for the PD community and is a perfect example of the hope in progress part of our organizations motto. It is thrilling to see the research that is underway, especially the potential treatments that have already made it to the clinical trial phase of development. However, this progress brings with it the welcome challenge of keeping track of all the potential compounds that are in research development! Recently, a review was published in the Journal of Parkinsons Disease which cataloged the 145 compounds that are currently being studied in humans via clinical trials for PD. This is a staggering number and is even more exceptional when you consider the many more compounds that are not quite yet ready for human trials, but are currently being studied in the laboratory in test tubes, cell culture or animal models of PD. The number also does not account for compounds that have been studied in small clinical trials, garnered promising data, and will be studied in larger clinical trials in the near future but are not being tested in clinical trials right now.
Some background on the review
Clinical Research On Prodromal Parkinsons Disease
In the clinical situation, manifest PDaccording to Braaket al.is preceded by years, if not decades, by prodromal phases. To screen for prodromal phases, the NMS hyposmia, constipation, depression, and the sleep-dream phase disorder RBD are now considered prodromal indicators. Whereas the first three are sensitive but not specific, RBD is now accepted as the most specific phenotype of the PD prodromal phases with a risk of more than 80% to convert into PD, or dementia with Lewy bodies or less frequently into multiple system atrophyin 10 to 15 years,. Similar research on prodromal stages takes place with at risk relatives of Parkinson patients, who are either heterozygous for theLRRK2 gene or are homozygous for one of the autosomal-recessive genes for a mitochondrial dysfunction in PD or possess a mutation of the gene for glucocerebrosidase 1 and thus are classified as PD-GBA1.
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The Search For An Objective Test
The need for objective Parkinsons disease tests, or biomarkers , has become more urgent as more projects enter human testing. Objective disease tests would speed drug development by identifying people most likely to respond to treatment, tracking disease progression and assessing therapeutic impact.
The Parkinson’s Progression Markers Initiative is the Foundations landmark public-private partnership to identify and validate biomarker candidates and develop tests to selectively and specifically measure Parkinsons pathology and symptoms. PPMI has become a world model for Parkinsons study design, lending the field groundbreaking tools and insights such as the use of dopamine scans as an early PD progression marker, the identification of factors that may predict cognitive decline, and even best practices in how to effectively recruit patients and controls for clinical studies an ongoing challenge in Parkinsons research.
Work is ongoing in pursuit of advanced brain imaging tracers that would allow scientists to visualize key cellular entities in the living brain. A similar tracer has been fundamental to recent progress in Alzheimer’s therapeutic development and holds potential to transform diagnosis, track disease and provide therapeutic assessment in people with Parkinson’s as well as atypical parkinsonisms such as Lewy body dementia and progressive supranuclear palsy .
Multifunctional Agents With D2/d3 Receptor Agonist Antioxidant Or Iron Chelating Activities
Compared with ropinirole, D512 exhibits superior peak-dose efficacy and longer duration effects in improving the rotational activity in the 6-OHDA-induced unilaterally lesioned rat model despite having similar side effects, including drug-induced dyskinesia. In addition, D512 protects dopaminergic MN9D cells from MPP+- and 6-OHDA-induced toxicity, inhibits lipid peroxidation and caspase 3/7 activity, and rescues 6-OHDA-induced changes in nuclear morphology. Moreover, D512 protects rat adrenal pheochromocytoma PC12 cells from 6-OHDA-induced apoptotic cell death and rescues dopaminergic neurons in the MPTP mouse model of PD. Furthermore, D512 displays neuroprotective effects against oxidative insult produced by buthionine sulfoximine, an inhibitor of glutathione synthesis, and 6-OHDA in PC12 cells.
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Box 1 Cardinal Motor Features Of Parkinson’s Disease
Bradykinesia/akinesia
Slowness of movement, fatiguing with decreased amplitude of movement, arrests in ongoing movement
Decreased spontaneous movements such as eye blinking, swallowing, and arm swing
Early feature
Tremor
Rhythmic sinusoidal movement of a body part due to regular contractions of reciprocally innervated muscles
Occurs at rest
Increase in resistance to passive movement
Cogwheel
Patients may complain of stiffness but not a major source of disability
Early feature
Postural instabilityretropulsion, propulsion, falls
Late feature
Shuffling, lack of arm swing
Festination: going from walking to running
Freezing: Feet sticking to the floor like glue, occurs with turning, gait initiation, enclosures like doorways
Late feature
Neurorestorative Growth Factor Therapies For Parkinsons Disease
Trophic factors are members of a class of proteins that promote development, growth, survival, and restoration of neurons in the CNS . Because of these properties, they are often seen as key therapeutic tools for neurorestorative therapies in the CNS. The first of these trophic factors was nerve growth factor , with many others following in recent decades . It is now well known that these factors display a wide range of structural, biochemical, pharmacological and biological properties in the CNS.
Growth factors are grouped into two main families: the neurotrophin family, which includes NGF, brain-derived neurotrophic factor , neurotrophin-3, and neurotrophin-4/5, and the glial cell-derived neurotrophic factor family, which comprises four main trophic factors, GDNF, neurturin , artemin, and persephin .
BDNF and mesencephalic astrocyte-derived neurotrophic factor are two other targets of interest for the possible development of growth factor-based therapies for PD patients . A summary of the key findings related to neurorestorative therapies in PD is shown in .
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Recent Advances In Parkinson’s Disease
Brain neurotransmitters.
Parkinson.org
Parkinsons disease is a progressive neurodegenerative disease that induces symptoms of shaking, stiffness, uncontrollable movement, poor coordination, and balance. Development of Parkinsons disease occurs at the age of 60 onward. This brain disorder develops as early as 50 years old in 5-10% of cases. Parkinsons affects nerve cells deep in the brain called basal ganglia. These cells are responsible for producing dopamine and transmitting messages for bodily functions.
Current treatments replace dopamine to the brain of a patient. Such treatments have been successful at reducing symptoms of nausea. At present, there is no cure for this brain disorder. It is important to manage Parkinsons early on, one new discovery that may help is the use of diagnostic tools.
Early detection of Parkinsons Disease
Biomarkers can be used as a diagnostic tool for identifying the stage of a disease in a patient with abnormal conditions. Researchers at Kobe and Hiroshima University developed a biomarker that detects early Parkinsons in patients’ blood serum samples such it is a quick and inexpensive process as outlined in figure 1.
Figure 1. Changes in P450 expression
https://neurosciencenews.com/parkinsons-biomarker-20673/
Figure 2. P450 inhibition assay process
https://neurosciencenews.com/parkinsons-biomarker-20673/
Model Analysis
Figure 3. Results of analysis using Parkinsons disease model rats and humans with Parkinsons … disease.
Search For Primary Endpoints Reflecting The Progression Of Parkinsons Disease In The Prodromal Stages
Taking together the discoveries on the genetic background of PD and the Braak staging hypothesis, new avenues for drug development and clinical testing have opened up. For clinical testingat least in the next few yearspotential disease-modifying compounds are and will be tested in the early stage of motor PD that is, very earlyde novo PD patients, who never received a symptomatic therapy will be recruited and should present with a unilateral asymmetric very mild motor symptomatology.
However, for true neuroprevention , parameters and biomarkers which reflect the progression of the alpha-synucleinopathy in the prodromal stage have to be discovered. In addition, such a parameter must be responsive to therapy, even in the prodromal stage, in order to qualify as a primary endpoint for pivotal registration trials. At present, such a parameter has not been identified. Respective research ranges from studies on biomarkers in the cerebrospinal fluid, peripheral blood, saliva, and sweat and in biopsies of the colonic enteric nervous system, the salivary gland, or the skin. Major efforts are placed into different imaging techniques with sophisticated magnetic resonance methods, nuclear medical ligands for the dopamine transporter single-positron emission computed tomography or fluoro-desoxyglucose positron emission tomography.
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The Latest Developments In Parkinsons Treatment: What Patients And Caregivers Need To Know
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Its devastating to watch a loved one live with Parkinsons disease. The progressive condition doesnt just affect the person with the diagnosis its also hard on caregivers, who are often forced to make difficult decisions on how to care for their loved one.
Medications for Parkinsons can significantly help the motor issues associated with the disease. Current Parkinsons treatments only fight symptoms, however they do nothing to stop the progression of the disease, which is caused by a loss of neurons.
Research on potential causes of and treatments for Parkinsons disease is ongoing. Recent research has shown a possible link between pesticide exposure and the development of Parkinsons disease, particularly in regards to the pesticide paraquat. Researchers are hopeful that new treatment protocols continue to effectively fight the symptoms of Parkinsons disease-related to pesticide exposure.
Parkinsons disease research can be devastatingly slow. To speed treatment research, the Coalition Against Major Diseases has created a data-sharing partnership between non-profits, pharmaceutical companies, and government organizations to spearhead Parkinsons research in the most efficient way possible.
Here, well explore the latest treatments for Parkinsons disease, as well as the treatment advancements that are likely to be made in the coming years.
Scientists Take The Next Step In Unraveling The Relationship The Protein Plays In The Disease
minute read.
An international team of scientists is advancing research in Parkinson’s disease. Today, the team released a new study outlining research that could potentially change the future of treating patients.
Currently, there are no disease-modifying therapies for Parkinsons disease that can change the progression of the disease. An international team of scientists led by faculty at the University of Colorado Anschutz Medical Campus is hoping to change that.
Today, the team published new research in the journal Brain that takes scientists one step closer to understanding -synuclein , a key protein that they found links inflammation and Parkinsons disease.
The protein Syn is predominantly expressed in neurons and is associated with neurodegenerative diseases, such as Parkinsons disease and dementia with Lewy bodies. This new study identifies the novel mechanism that links interferon activation and Syn function in neurons as a potential trigger for developing Parkinsons disease.
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Studies Show Promising Results
“Considering the ability of MSCs to secrete neurotrophic factors, modulate inflammation, and possibly even act as mitochondria âdonorâ, it comes as no surprise that there is a lot of interest in the use of MSCs in the treatment of Parkinsons Disease, and a multitude of animal studies has shown promise. Treatments have resulted in improvement of motor function, protection of the nigrostriatal system, and improved striatal dopamine release in several studies using toxic lesion rodent models of Parkinsons Disease. Similar effects were reported with umbilical cord-derived MSCs with or without prior differentiation. For example, a recent study reported improvement of motor function, reduced microglial activation, and decreased loss of TH immunoreactivity, associated with local production of trophic factors.
Learn more about DVC Stem’s protocol for Parkinson’s Disease here:
References:
Venkataramana, N. K., Kumar, S. K. V., Balaraju, S., Radhakrishnan, R. C., Bansal, A., Dixit, A., ⦠Totey, S. M. . Open-labeled study of unilateral autologous bone-marrow-derived mesenchymal stem cell transplantation in Parkinson’s disease. Retrieved from https://www.sciencedirect.com/science/article/pii/S1931524409002205#!
Unified Parkinson’s Disease Rating Scale. . Retrieved from https://www.sciencedirect.com/topics/medicine-and-dentistry/unified-parkinsons-disease-rating-scale
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