Tuesday, November 22, 2022

New Developments In Parkinson’s Disease Treatment

The History Of Parkinsons

New Developments & Future Treatments in PD – Dr. Anthony Lang – UF Parkinson Symposium 2018

Parkinsons disease was first defined as a shaking palsy in 1817 by James Parkinson. Half a century later, in 1872, the Parisian neurologist Jean-Martin Charcot coined the term Parkinsons disease.

Though Parkinson was the first to describe the disease in modern medicine, Charcot and his colleagues revolutionised treatments in the mid-19th century.. Parkinson was a proponent of blood-letting from the neck, in a bid to siphon off inflammatory pathogens and prevent them from reaching the brain. But Charcot and his colleagues favoured pharmaceutical approaches centred around anticholinergic drugs, which block the action of a neurotransmitter called acetylcholine. Anticholinergics are still in use today.

Around the same time, a host of other treatments were being explored at a hospital in Paris. Hyoscyamine, a plant-derived medication, was put in bread and fed to patients. Other medications, such as a derivative of quinine, were mixed with a syrup of orange rinds.

Charcot also claimed to see the symptoms of patients with Parkinsons improving when travelling by train and horse-carriage. He became a proponent of vibration therapy, where patients bodies and heads were shaken vigorously by a rigged motor.

Parkinsons Surveys Clinical Trials And Volunteer Opportunities

PAIRing Up If you are a person with Parkinsons or a care partner to someone with Parkinsons, you are invited to participate in an online survey to address neuropsychiatric concerns in Parkinsons. The survey aims to learn about the needs and priorities for clinical care, education, support, and research as related to neuropsychiatric symptoms. To learn more and participate, .

The University of Oulu, along with collaborators from Aalborg University, Fraunhofer University, the University of Manchester, the University of Glasgow, the University of Lisbon, and the University of Melbourne, is conducting a survey for people with Parkinsons and Parkinsons care partners about self-care. Complete the survey here to share your self-care strategies and techniques. You can also review ideas submitted by others and add them to your own self-care toolbox.

Looking for a once-in-a-lifetime adventure? Pass to Pass, a nonprofit dedicated to raising Parkinsons awareness while supporting hikers living with Parkinsons, offers multi-day hiking trips on the Pacific Crest Trail in both Washington and Oregon. Participants are being recruited now for these summer 2021 events. For more details and information, visit www.PasstoPass.org or contact Bill Meyer at 509-991-1212 or .

Park Test University of Rochester

Project Euphonia LSVT Global and Project Euphonia

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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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.

Search For Parkinsons Disease

Frontiers

The ultimate therapeutic challenge remains. Every person who knows a patient with PD asks why there is not a treatment that prevents the motor manifestation of PD. Already-diagnosed PD patients and their families dream of a treatment that can slow down or even partially reverse the progression of this devastating disorder with all its motor and non-motor symptoms and complications in the advanced stage. These dreams may be fulfilled in the not-too-distant future.

Two therapeutic strategies are currently followed. The first is based on epidemiological findings and large clinical prospective trials reporting a correlation between a reduced occurrence or prevalence of PD and the consumption of compounds such as caffeine or nicotine . lists examples of these generic substances with a postulated disease-modifying potential for PD.

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Levodopa In The Treatment Of Parkinson’s Disease: Current Status And New Developments

Article type: Review Article

Authors: Salat, David | Tolosa, Eduardo

Affiliations: Universitat Autònoma de Barcelona, Barcelona, Spain | Parkinson’s Disease and Movement Disorders Unit, Neurology Service, Hospital Clínic, University of Barcelona Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas Barcelona, Spain

Note: Correspondence to: Eduardo Tolosa MD, FRCP, Neurology Service, Hospital Clinic, University of Barcelona, Villarroel 170, Barcelona 080036, Spain. Tel.: +34 93 227 57 85 Fax: +34 93 227 57 83 E-mail:

Keywords: Levodopa/carbidopa, Parkinson’s disease, wearing-off, dyskinesia, entacapone

DOI: 10.3233/JPD-130186

Journal: Journal of Parkinson’s Disease, vol. 3, no. 3, pp. 255-269, 2013

Abstract

What Diseases And Conditions Resemble Parkinsons Disease

PD is the most common form of parkinsonism, in which disorders of other causes produce features and symptoms that closely resemble Parkinsons disease. Many disorders can cause symptoms similar to those of PD, including:

Several diseases, including MSA, CBD, and PSP, are sometimes referred to as Parkinsons-plus diseases because they have the symptoms of PD plus additional features.

In very rare cases, parkinsonian symptoms may appear in people before the age of 20. This condition is called juvenile parkinsonism. It often begins with dystonia and bradykinesia, and the symptoms often improve with levodopa medication.

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Reasons Parkinson’s Disease Can Occur

When a loved one is living with Parkinsons, its natural to wonder what caused the disease to take root. Although most cases of Parkison’s have an unknown cause, a very small percent of cases can be hereditary . Some studies have linked long-term exposure to pesticides, including one called paraquat, with an increased likelihood of the development of Alzheimers and Parkinsons disease.

The pesticide was first introduced in the United States in the 1950s and is still used commonly by licensed users today. If you think that your loved one who has been diagnosed with Parkinsons may have been exposed to paraquat, its important that you work with a lawyer to learn whether you may be eligible for compensation. Caring for a loved one with Parkinsons can be costly and time-consuming, especially in the later stages when your loved one requires around-the-clock care. Financial compensation can make it easier to provide your loved one with the care they deserve throughout the progression of the disease.

Were here to help you decide what to do next after you find out that paraquat exposure may be responsible for the development of Parkinsons disease in your loved one. Reach out to us today for a free case review.

New Medications For Off Time

Parkinsons Disease: New Developments and Therapies – On Our Mind

A number of new medications approved recently are designed to reduce OFF time. These medications fall into two major categories:

  • Medications that lengthen the effect of a carbidopa/levodopa dose
  • Medications that are used as needed if medication effects wear off

Well give specific examples below. In general, new medications that extend the length of a carbidopa/levodopa dose are used if OFF time is somewhat predictable and occurs prior to next dose. New medications that are used as needed are most beneficial when OFF time is not predictable.

New medications that lengthen the effect of a dose of carbidopa/levodopa

  • Istradefylline is an adenosine A2A receptor antagonist which was approved in the US in 2019 as an add-on therapy to levodopa for treatment of OFF time in PD. Unlike many of the other medications, it has a novel mechanism of action and is the first medication in its class to be approved for PD. It acts on the adenosine receptor, which modulates the dopaminergic system, but is not directly dopaminergic. The drug was developed in Japan and underwent clinical trials both in Japan and in the US.
  • Opicapone is a catechol-O-methyltransferase inhibitor that is taken once a day. It was approved in the US in 2020 as an add-on therapy to levodopa for motor fluctuations.

New formulations of levodopa designed to be used as needed if medication effects wear off

Other medications used as needed if medication effects wear off

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Organization Publishes New Guidelines For The Treatment Of Early Parkinsons Disease

The American Academy of Neurology has published guidelines that provide recommendations for treating motor symptoms called motor symptoms in people with early Parkinsons disease. The guidelines are published online on November 15, 2021. Neurology, AAN Medical Journal, endorsed by the Parkinsons Foundation. This guideline updates the dopamine agonist recommendations published in the 2002 AAN Guidelines for Initiating Treatment for Parkinsons Disease.

Parkinsons disease can gradually affect all movements, including manual dexterity, speech, walking, and balance, as the chemicals in the brain gradually diminish. Dopamine, A substance that helps control movement. Early-stage motor symptoms of Parkinsons disease include tremor, stiffness, and bradykinesia. This is slow movement. To alleviate these early symptoms process Options include dopamine agonists, drugs that raise dopamine levels, or drugs that mimic the effects of dopamine.

The guidelines recommend that neurologists advise people with early-stage Parkinsons disease on the benefits and risks of the following three initial treatments: Treatment options: Levodopa, a drug that is converted to dopamine in the brain. Dopamine agonist, a drug that mimics the effects of dopamine a monoamine oxidase B inhibitor, a drug that prevents an enzyme called MAO-B from degrading dopamine.

The guidelines state that medication may help alleviate motor symptoms.

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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New Treatment May Have The Potential To Slow Stop Or Reverse Parkinson Disease

Results from a recent study suggest that a revolutionary treatment may have the potential to slow, stop, or even reverse the progression of Parkinson disease.

Results from a February study of a revolutionary treatment suggest that it may be possible to slow, stop, or even reverse the progression of Parkinson disease, according to findings in the Journal of Parkinsons Disease.

The 3-part, experimental study investigated whether using a novel delivery system to increase levels of glial cell line-derived neurotrophic factor can regenerate dying dopamine brain cells in patients with Parkinson disease and even reverse their condition. GDNF is a naturally occurring protein that promotes the survival of many types of neurons.

I believe that this approach could be the first neuro-restorative treatment for people living with Parkinson’s, which is, of course, an extremely exciting prospect, Steven Gill, MB, MS, FRCS, who designed the infusion device used in the study, said in a statement.

Initially, 6 patients enrolled in a pilot study which evaluated the safety of the treatment approach. After the pilot study, 35 additional individuals participated in a subsequent 9-month double-blind trial. Half of the participants were randomly assigned to receive monthly infusions of GDNF while the other half received placebos.

Reference

Potential Breakthrough In The Treatment Of Parkinsons Disease Drug Candidate Cdnf Could Stop The Progression Of The Disease And Improve Symptoms

Is stem cell therapy effective for Parkinson

The novel drug candidate CDNF, discovered at the Institute of Biotechnology, University of Helsinki, could be a disease-modifying treatment of Parkinsons disease in addition to alleviating its symptoms. Such a breakthrough would also have significant social implications. In Finland, approximately 14 000 patients suffer from Parkinsons disease, and thus far, there is neither a cure nor a treatment that can slow the progression of this disease.

CDNF could be a breakthrough in the treatment of Parkinsons disease. Currently in its first clinical study in Finland and Sweden, the first results indicate that CDNF can protect and even restore dopaminergic neurons, slow the progression of Parkinsons disease, and alleviate its symptoms.

CDNF is a protein naturally found in the human brain and circulation. It plays an important role in neuronal survival. Parkinsons disease is caused by the loss of dopamine-producing neurons thus, CDNF targets the root cause of the disease. This new drug candidate differs from known anti-Parkinsons drugs in that it targets true disease modification in addition to symptomatic relief. Going forward, it could even stop disease progression.

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What Are The Symptoms Of The Disease

The four primary symptoms of PD are:

  • Tremor. Tremor often begins in a hand, although sometimes a foot or the jaw is affected first. The tremor associated with PD has a characteristic rhythmic back-and-forth motion that may involve the thumb and forefinger and appear as a pill rolling. It is most obvious when the hand is at rest or when a person is under stress. This tremor usually disappears during sleep or improves with a purposeful, intended movement.
  • Rigidity. Rigidity , or a resistance to movement, affects most people with PD. The muscles remain constantly tense and contracted so that the person aches or feels stiff. The rigidity becomes obvious when another person tries to move the individuals arm, which will move only in ratchet-like or short, jerky movements known as cogwheel rigidity.
  • Bradykinesia. This slowing down of spontaneous and automatic movement is particularly frustrating because it may make simple tasks difficult. The person cannot rapidly perform routine movements. Activities once performed quickly and easilysuch as washing or dressingmay take much longer. There is often a decrease in facial expressions.
  • Postural instability. Impaired balance and changes in posture can increase the risk of falls.

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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Advanced And Future Treatments For Parkinsons

While theres no cure for Parkinsons disease, recent research has led to improved treatments.

Scientists and doctors are working together to find a treatment or prevention technique. Research is also seeking to understand who is more likely to develop the disease. In addition, scientists are studying the genetic and environmental factors that increase the chance of a diagnosis.

Here are the latest treatments for this progressive neurological disorder.

In 2002, the FDA approved deep brain stimulation as a treatment for Parkinsons disease. But advances in DBS were limited because only one company was approved to make the device used for the treatment.

In June 2015, the FDA approved the

Frontiers In Aging Neuroscience

New Advances Make DBS Therapy More Effective For Treating Parkinson’s Disease

National Institute on Aging, National Institutes of Health , United States

Reviewed by

Northwestern University, United States

The editor and reviewers’ affiliations are the latest provided on their Loop research profiles and may not reflect their situation at the time of review.

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What Genes Are Linked To Parkinsons Disease

Several genes have been definitively linked to PD:

  • SNCA. This gene, which makes the protein alpha-synuclein, was the first gene identified to be associated with Parkinsons. Research findings by the National Institutes of Health and other institutions prompted studies of the role of alpha-synuclein in PD, which led to the discovery that Lewy bodies seen in all cases of PD contain clumps of alpha-synuclein. This discovery revealed the link between hereditary and sporadic forms of the disease.
  • LRRK2. Mutations in LRRK2 were originally identified in several English and Basque families as a cause of a late-onset PD. Subsequent studies have identified mutations of this gene in other families with PD as well as in a small percentage of people with apparently sporadic PD. LRRK2 mutations are a major cause of PD in North Africa and the Middle East.
  • DJ-1. This gene normally helps regulate gene activity and protect cells from oxidative stress and can cause rare, early forms of PD.
  • PRKN . The parkin gene is translated into a protein that normally helps cells break down and recycle proteins.
  • PINK1. PINK1 codes for a protein active in mitochondria. Mutations in this gene appear to increase susceptibility to cellular stress. PINK1 has been linked to early forms of PD.
  • GBA . Mutations in GBA cause Gaucher disease , but different changes in this gene are associated with an increased risk for Parkinsons disease as well.

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