Editorial Note On The Review Process
F1000 Faculty Reviews are commissioned from members of the prestigiousF1000 Faculty and are edited as a service to readers. In order to make these reviews as comprehensive and accessible as possible, the referees provide input before publication and only the final, revised version is published. The referees who approved the final version are listed with their names and affiliations but without their reports on earlier versions .
The referees who approved this article are:
Fredric P. Manfredsson, Parkinsons Disease Research Unit, Department of Neurobiology, Barrow Neurological Institute, Phoenix, Arizona, USA
No competing interests were disclosed.
Tipu Z. Aziz, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
No competing interests were disclosed.
How We’re Speeding Up The Search For A Cure
We believe that new and better treatments are possible in years, not decades. We have a clear strategy for making this happen. This includes:
- Backing the best and brightest minds to unlock scientific discoveries that will lead to new treatments and a cure.
- Accelerating the development and testing of new treatments through our Virtual Biotech.
- Collaborating internationally to make clinical trials faster, cheaper and more likely to succeed through the Critical Path for Parkinson’s.
- Tracking down drugs for other conditions which have untapped potential for Parkinson’s.
We know that the more we’re able to invest, the faster we’ll be able to deliver. So we’re working hard to raise the funds we need to drive things forward faster.
The Latest In Parkinsons Medications: Taking A Personalized Approach
From renowned singer Linda Ronstadt to former NBA player Brian Grant, the faces of Parkinsons disease are as diverse as the symptoms. While there can be common themes such as slowed movement or stiffness each persons PD experience is unique, making individually tailored therapy vital. Fortunately, the list of medications and treatments that improve quality of life for people living with PD continues growing.
This article is based on a Parkinsons Foundation Expert BriefingParkinson’s Disease & Medication – What’s Newpresented by Vanessa K. Hinson, MD, PhD, Movement Disorders Program director, Medical University of South Carolina, a Parkinsons Foundation Center of Excellence.
Parkinsons disease can vary widely from one person to another. Whether or when someone might experience rapid, involuntary and uncontrollable body movements, called dyskinesias, as a complication of some Parkinsons medications can also fluctuate. Cognitive changes or multitasking can pose challenges for some who live with PD, while others might experience hallucinations. Optimal PD treatment and care should be based on your unique symptoms and help you to live your best life.
Medical Moment: A New Treatment For Parkinsons
SOUTH BEND, Ind. – Around one million people in the U.S. live with Parkinsons disease.
Levodopa is the most effective drug available, but the drug can cause side effects, and after several years, the effectiveness of Levodopa can wane and higher dose patients may develop dyskinesia, or involuntary, erratic movements.
Now, a new drug, currently in clinical trials, may reduce these unpleasant side effects while lengthening the time patients have relief of their symptoms.
70-year-old Wayne Holt has been living with Parkinsons disease for 21 years.
I used to be a racquetball player and I couldnt keep up with the ball anymore, Holt said. I decided I needed to find a sport where the ball sits still until I hit it.
Holt first noticed his Parkinsons symptoms when he was at lunch with a friend.
When I lift my drinking glass, my hand really had a tremor to it, Holt recalled.
Parkinsonian tremors are due to too much brake and not enough gas. When people try to do personal movement, they get shaking because the brake is being applied as theyre trying to apply the gas, said Craig Lindsley, PhD, a director at the Warren Center for Neuroscience Drug Discovery.
But researchers are testing a new drug called AP472.
This is really different because its not dopamine replacement therapy, Dr. Lindsley said. Were targeting this overactive synapse and bringing that gas and brake back into balance.
For Holt, who suffers with dyskinesia, a drug like this can be a game-changer.
A Treatment Thats All In Your Head
Strick believes the placebo effect deserves more respect than it often gets.
I love it when people say its all in your head, because your brain is in your head, he says. There are real biological underpinnings for these kinds of things.
So Strick has assembled a team of prominent scientists to find the biological underpinnings of paradoxical kinesia. The team hopes what they learn will lead to new treatments for Parkinsons disease, which affects nearly 1 million people in the U.S.
The effort involves several labs at the University of Pittsburgh and one at the University of California, Santa Barbara. Its being funded by a $12 million grant from the Aligning Science Across Parkinsons Initiative and implemented by the Michael J. Fox Foundation.
Stricks collaborators plan to focus on two circuits in the brain that appear to control voluntary movement. One is damaged by Parkinsons, leading to symptoms including tremor, freezing, and poor balance and coordination.
Our hypothesis is that theres another circuit thats intact, and that this circuit isnt affected in Parkinsons disease, Strick says.
Stricks team believes this other circuit can be switched on by strong emotions, including positive ones.
Its engaged by our sense of reward, by the joy of doing something, he says.
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Failure Of Two Agents In Two Phase Ii Trials Could Spell The End For One Avenue Of Treatment
byCrystal Phend, Contributing Editor, MedPage Today August 3, 2022
Similarly designed phase II trials of two investigational alpha-synuclein targeted biologics dashed hopes for disease-modifying monoclonal antibody drugs in early-stage Parkinson’s disease.
In the SPARK trial, cinpanemab failed to hit either primary endpoint for change in the sum of scores on parts I, II, and III of the Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale total score, reported Tien Dam, MD, of drug developer Biogen in Cambridge, Massachusetts, and colleagues.
No significant change occurred from baseline to week 52 or at week 72 .
In the PASADENA trial, prasinezumab also did not significantly change the same endpoint from baseline to week 52 , reported Gennaro Pagano, MD, PhD, of the Roche Innovation Center Basel in Switzerland, and colleagues. A delayed-start cohort yielded similarly negative results.
The effect wasn’t meaningful overall for imaging measures, both groups concluded in the studies published together in the New England Journal of Medicine.
The results were “more than disappointing and certainly have no implications for current practice,” noted Alan Whone, PhD, of the University of Bristol and Southmead Hospital in Bristol, England, in an accompanying editorial.
Biogen announced it was discontinuing development of cinpanemab.
Both trials enrolled patients in North America and Europe, with the addition of Israel in SPARK.
Innovative Gel Offers New Hope To Defeat Parkinsons Disease
When we introduced the gel technology with the stem cells we saw huge improvement in the animals coordinated paw movement and overall motor function recovery.
Researchers from The Australian National University , in collaboration with The Florey Institute of Neuroscience and Mental Health, have developed a new type of hydrogel that could radically transform how we treat Parkinsons disease. The gel also offers hope for patients who have suffered from other neurological conditions such as strokes.
The new material is made from natural amino acids the building blocks of proteins and acts as a gateway to facilitate the safe transfer of stem cells into the brain and restore damaged tissue by releasing a growth-enabling protein called GDNF.
The research has been published in the journal Advanced Functional Materials.
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Drug And Medication Therapies
The purpose of treating Parkinsons is to reduce the effect of symptoms on your daily life. Without treatment, you will eventually find that the symptoms make it hard to perform daily activities. Symptoms, such as shaking and stiffness, may cause discomfort the risk of injury from falls may increase, and swallowing may become more difficult. People are encouraged to maintain open and ongoing discussions with their Parkinsons healthcare team when exploring treatment options.
Medication will help you function, but may cause side effects. It is important to find the right balance between the medications benefits and side effects. Everyone with Parkinsons is unique and will experience different symptoms, which means the treatment you receive will be geared to your specific needs. Drugs for Parkinsons work on the brains complex chemistry and may need to be taken several times a day. Use them as prescribed and do not alter your doses without consulting your doctor. Current treatment neither cures Parkinsons nor stops it from advancing.
How Is Parkinson’s Disease Treated
No treatment can stop or reverse the breakdown of nerve cells that causes Parkinson’s disease. But there are many treatments that can help your symptoms and improve your quality of life.
Your age, work status, family, and living situation can all affect decisions about when to start treatment, what types of treatment to use, and when to make changes in treatment. As your medical condition changes, you may need regular changes in your treatment to balance quality-of-life issues, side effects of treatment, and treatment costs.
You’ll need to see members of your health care team regularly to adjust your treatment as your condition changes.
Treatments for Parkinson’s include:
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Advances In Deep Brain Stimulation
Deep brain stimulation is another established treatment for PD that is useful in treating dopamine-dependent motor symptoms when levodopa-induced side effects become particularly problematic. DBS involves the surgical implantation of electrodes that stimulate subcortical structures including the subthalamic nucleus and globus pallidus internus9194. DBS offers significant improvements in motor symptoms and fluctuations in comparison to best medical therapy in some advanced PD patients, but dopamine-resistant symptoms other than tremor respond poorly95. It has also been suggested in an open-label trial that DBS is beneficial in early PD patients, with improved tremor scores and reduced development ofde novo tremor96. In addition to surgical complications, DBS strategies may cause cognitive and neuropsychiatric adverse effects as well as speech dysfunction. Novel DBS approaches, including adaptive DBS, targeting different regions, and refined intra-operative imaging techniques promise to offer improved clinical applicability and reduce the impact of adverse effects97.
New Treatments For Parkinsons Disease Off Episodes
If you have Parkinson’s disease, new treatment options might help you manage your symptoms more effectively. Even if you take antiparkinsonian medication successfully, most levodopa medications stop being effective after a while. When this happens, patients usually experience OFF periods where their symptoms temporarily return. To minimize the physical and emotional effects of the ON/OFF phenomenon, doctors are constantly testing out new treatment options for Parkinson’s disease. Let’s look at some of the latest drugs and how they might help you.
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Treatments In Phase Ii Trials
Another strategy in the therapeutic research space is drug repurposing. This is when an existing medication for one condition is repurposed to treat an entirely different condition. Working with repurposed medications comes with many advantages including understanding its general safety. Repurposing an existing medication, rather than starting from scratch, typically requires fewer tests for safety as the drug has already met these requirements. This can reduce costs and speed up the process through the clinical trial pipeline. It can also lead to faster approvals, getting much-needed treatments into the hands of people with Parkinsons as soon as possible. There are a total of 74 therapies in Phase II trials and 44% are repurposed medications.
One exciting takeaway from Phase II trials this year is the progress made with stem cell therapies. While there are nine stem cell therapies being explored in Phase I, two stem cell therapies graduated to Phase II trials this year! Moving into Phase II means these treatments are being administered to a larger group of people to monitor their effectiveness and further evaluate their safety.
What Will A Cure For Parkinsons Look Like
Parkinsons varies so much from person to person. There are over 40 symptoms of Parkinsons. Tremor. Pain. Hallucinations. Everyones experience is different.
Because of this, there may not be a single cure.
Instead we may need a range of different therapies to meet the needs of the individual and their specific form of the condition.
This mix may include treatments, therapies and strategies that can:
- slow or stop the progression of the condition
- replace or repair lost or damaged brain cells
- control and manage particular symptoms
- diagnose Parkinsons at the earliest possible stage.
And this could involve medical treatments, such as drugs and surgical approaches, as well as lifestyle changes, for example to diet and exercise.
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Parkinsons Disease Treatment Options
Parkinsons is incurable, but the symptoms can be managed as the disease progresses. Initially, your doctor may recommend lifestyle changes, such as ongoing aerobic exercise, healthy diet, and advice for avoiding falls.
Carbidopa-levodopa : Sometimes simply called Levodopa, is the most effective Parkinsons disease medication and has been since its breakthrough in the late 1960s. It is an effective first-line treatment for Parkinsons and comes in many formulations, including slow- and extended-release pills, and infusions. It works by introducing a natural chemical to the body which converts into dopamine in the brain. This helps reduce symptoms of stiffness and tremors. The medication does not slow the progression of the disease.
Catechol O-methyltransferase inhibitors: These pills can boost the effectiveness of carbidopa-levodopa. It helps block the brains dopamine breakdown to help reduce some of the tremors and motor symptoms of Parkinsons.
Dopamine agonists: This medication mimics the effect of dopamine in the brain and may be used with carbidopa-levodopa. It can be prescribed in the early stages of Parkinsons, and it can lengthen the effectiveness of carbidopa-levodopa.
Innovative surgical options
Amneal Tests A New Formulation
AmnealPharmaceuticals plans to report Phase III safety results for IPX-203, a reformulation of the common generic PD treatment combination of carbidopa and levodopa that could reduce symptom fluctuations. The company said the Phase III, open-label extension study will have results available by the end of the second quarter of 2022.
CD/LD can lead to troughs and spikes of plasma levels that generate side-effects like dyskinesia, Kordower explains. A new extended-release version of CD/LD could smooth out these drops, he notes.
If approved, IPX-203 will join several other marketed reformulations of CD/LD. Amneals own extended-release capsule Rytary, Schwarz Pharma s orally disintegrating tablet Parcopa, and AbbVie’s enteral suspension Duopa all have FDA approval in PD. A GlobalData consensus forecasts pegs peak IPX-203 sales at $127 million in 2028.
In a separate, placebo-controlled Phase III trial , IPX-203 resulted in 0.53 more hours of ON time than immediate-release CD/LD after seven weeks . Earlier, a six-week Phase II trial of IPX-203 reported no serious treatment-emergent adverse events among the 26 patients enrolled. Experts say the long-term safety data will be key in determining IPX-203s place among CD/LD formulations.
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Surgery For Parkinsons Disease
Based on the severity of the condition and the medical profile, the doctor may recommend surgery as one treatment option for Parkinson’s disease.
There are several types of surgery that may be performed that can help patients with Parkinson’s disease. Most of the treatments are aimed at helping the tremor or rigidity that comes with the disease. In some patients, surgery may decrease the amount of medication that is needed to control the symptoms.
There are three types of surgeries that may be performed for Parkinson’s disease, including the following:
It is important to remember that surgery may help with symptoms of Parkinson’s disease, but does not cure the disease or stop the progression of the disease.
Treatments In Phase Iii Trials
What we see in Phase III trials this year is a total of 22 treatments from five different therapeutic categories. Three treatments in Phase III are disease-modifying treatments that have the potential to alter the progression of Parkinsons disease. One is widely used in traditional Chinese medicine, one is a repurposed Alzheimers medication, and the other is a repurposed diabetes medication.
There are also 19 studies in Phase III addressing symptoms of Parkinsons. While the community waits for gains to be made with disease-modifying treatments, improvements in symptom relief are critical for maintaining the quality of life. more personalized treatment plans If the symptom management products in Phase III safely and successfully complete their trials, the medical community will have more tools available to support Parkinsons symptom management.
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New Parkinsons Disease Treatments 2021
You can legally access new medicines, even if they are not approved in your country.
New Form Of Drug Helping Some Patients With Parkinsons Disease
For more than 40 years, a drug called levodopa has been the most effective treatment for the uncontrolled movements associated with Parkinsons disease. Many Parkinsons patients have taken a pill form of the medicine also known as L-dopa for years to control their motor fluctuations.
But the pills can lose effectiveness over time, greatly reducing their value for people in the later stages of the disease.
Now theres a new form of the drug that is making a positive difference for some Parkinsons patients. Duopa is a drug thats delivered continuously by a pump system instead of pills.
This takes care of the fluctuations in the movement symptoms that advanced Parkinsons patients experience on a daily basis, and they dont have to rely on pills while the pump is on, said movement disorders specialist Dr. Mustafa Saad Siddiqui, an associate professor of neurology at Wake Forest Baptist. It can mean a very significant improvement in the quality of life of these patients.
Parkinsons disease is a degenerative disorder of the brain cells that produce dopamine, a chemical that helps people control body movements. While tremors are the best-known sign of Parkinson’s, it can also cause muscle rigidity and slowing of movement. There is no cure for the disease, which afflicts approximately 1 million people in the United States, including actor Michael J. Fox and boxing legend Muhammad Ali.