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.
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A New Era for Parkinsons Disease Treatment
Expert Voices: Integrative Medicine For People With Parkinsons Disease
NRG has a pipeline of orally available small molecules designed to reach cells of the brain and spinal cord, referred to as the central nervous system, and block the mitochondrial permeability transition pore . This protein forms on the inner membrane of energy-producing mitochondria and, when open due to an accumulation of calcium or other stimuli, can lead to cell death.
What has limited the pharmaceutical industry to date from exploring mPTP inhibitors as novel therapeutic treatments, has been the poor central nervous system penetration of known mPTP inhibitors, Roach said. NRGs small molecules are the first orally bioavailable and CNS-penetrant inhibitors of the mPTP.
mPTP has been implicated in Parkinsons, caused by the death of brain cells that produce dopamine, a neurotransmitter produced by the body to send messages between nerve cells to control movement, learning and memory, sleep, and mood.
The potential therapies may also help with the neurodegenerative disorder amyotrophic lateral sclerosis , also known as motor neuron disease, caused by the death of nerve cells that control voluntary movements.
Mitochondrial dysfunction is a common underlying pathology in many degenerative diseases and there is a substantial body of preclinical data available which demonstrates that inhibition of the mPTP in the brain prevents neuronal cell death, reduces neuroinflammation and extends survival in animals, said Neil Miller, PhD, NRGs co-founder and CEO.
New Drug Shows Promise In Treating Parkinson’s Disease Psychosis
Off-label drugs have been used to manage psychotic-related symptoms in Parkinson’s disease patients, but they worsen motor symptoms by reducing dopamine levels. Nuplazid is the only FDA-approved drug that treats Parkinson’s disease psychosis without impairing motor function.
Parkinson’s disease is a progressive neurodegenerative condition marked by bradykinesia, rigidity, tremor, and postural instability. While therapeutic advances have been made to improve motor-related symptoms, many older adults affected by this disease also develop Parkinson’s disease psychosis . Psychotic symptoms such as hallucinations and delusions develop in more than 50% of PD patients and can lead to severe impairments in cognitive, behavioral, and emotional function.1
PDP Drives Nursing Home Placement According to the Parkinson’s Disease Foundation, 1 million people have been diagnosed with PD in the United States, and between 7 million and 10 million people worldwide have the condition. Hallucinations and delusions drive the nursing home placement and hospitalization of patients diagnosed with PDP, says Jason Kellogg, MD, chief of staff at Newport Bay Hospital in Newport Beach, California.
He adds that the delusions and hallucinations observed in PDP tend to be more dramatic in nature. For instance, these patients are usually high-functioning, well-dressed men and women. But their hallucinations are quite striking because they have delusions of persecution and visual hallucinations.
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Medication For Parkinsons Disease
Once the doctor diagnoses Parkinsons disease, the next decision is whether a patient should receive medication, which depends on the following:
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The degree of functional impairment
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The degree of cognitive impairment
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Ability to tolerate antiparkinsonian medication
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The advice of the attending doctor
No two patients react the same way to a given drug, therefore, it takes time and patience to find an appropriate medication and dosage to alleviate symptoms.
Stay Safe With Your Medicines
Read all labels carefully.
- Tell all your health care providers about all the medicines and supplements you take.
- Know all the medicines and foods youâre allergic to.
- Review any side effects your medicines can cause. Most reactions will happen when you start taking something, but thatâs not always the case. Some reactions may be delayed or may happen when you add a drug to your treatment. Call your doctor right away about anything unusual.
- Use one pharmacy if possible. Try to fill all your prescriptions at the same location, so the pharmacist can watch for drugs that might interact with each other.
- You can use online tools to see if any of your medicines wonât work well together.
You have the right and responsibility to know what medications your doctor prescribes. The more you know about them and how they work, the easier it will be for you to control your symptoms. You and your doctor can work together to create and change a medication plan. Make sure that you understand and share the same treatment goals. Talk about what you should expect from medications so that you can know if your treatment plan is working.
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What New Treatments Are Being Developed
Thanks to the progress we’ve already made, new treatments are being tested in clinical trials that have the potential to slow, stop or even reverse Parkinson’s.
These include:
- stem cell therapies, which aim to use healthy, living cells to replace or repair the damage in the brains of people with Parkinson’s
- gene therapies, which use the power of genetics to reprogramme cells and change their behaviour to help them stay healthy and work better for longer
- growth factors , which are naturally occurring molecules that support the growth, development and survival of brain cells.
And we’re developing treatments that aim to improve life with the condition, including new drugs that can reduce dyskinesia.
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.
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How Does It Work
In people with Parkinsons disease, the brain doesnt produce enough of a neurotransmitter called dopamine. The cells that produce dopamine either die or become impaired. Dopamine is necessary for proper motor control and movement.
Specifically, dopamine transmits signals in the brain that are involved in smooth, purposeful movements like eating, writing, and typing. Like selegeline and rasagaline, safinamide is a type of MAO-B inhibitor, which prevents the breakdown of dopamine and thus increases its levels in the brain.
Of note, safinamide also modulates glutamate release however, the specific effect of this action on the drugs therapeutic actions is unknown.
Unlike other MAO-B inhibitors, which can be prescribed alone for those with early-stage Parkinsons disease, safinamide is intended to be used in conjunction with other types of antiparkinson drugs for the later-stage disease, most notably levodopa as well as dopamine agonists.
When people first start treatment for Parkinsons symptoms, drugs tend to work pretty well and symptoms are controlled throughout the day. Between five and 10 years, however, the efficacy of conventional Parkinsons drugs wanes in many people, and symptom control becomes more difficult to alleviate.
Specifically, in people with mid- to late-stage Parkinsons disease, motor fluctuations or involuntary muscle movements begin to crop up.
Current Parkinsons Treatments Cant Slow Down Onset Of Disease
Parkinsons is a long-term degenerative disorder of the central nervous system, which mainly the area of the brain that controls movement leading to a slow onset of symptoms including tremors, rigidity and slow movement.
More than 10 million people worldwide are estimated to be living with Parkinsons disease, according to the US-based Parkinsons Foundation, with the Parkinsons News Today website saying it affects 1,900 per 100,000 among those aged over 80,
Typically, by the time people are diagnosed with the condition, they have already lost between 70% and 80% of their dopamine-producing cells, which are involved in co-ordinating movement.
While current treatments mask the symptoms, there is nothing that can slow down its progression or prevent more brain cells from being lost.
As dopamine levels continue to fall, symptoms get worse and new symptoms can appear.
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Searching To Control Symptoms: New Methods Of Delivery
In recent months, symptomatic treatment of PD has had some new developments as well. A new drug for PD, rotigotine, has been introduced in Europe and elsewhere as Neupro. This compound is a dopaminergic agonist, a class of drugs that also includes drugs that have been available for many years in the U.S., including Mirapex, Requip, and Permax . Neupro is unique in how it is delivered: it is absorbed through the skin and so has been marketed as a transdermal patch with continuous delivery over 24 hours. So far, experience with Neupro suggests that it is effective and well tolerated. However, whether this drug or its unique mode of delivery will offer a significant advantage over currently marketed medications of the same class still remains to be learned.
PD still presents many challenges for the medications of the future. Among the unmet needs are ways to reverse the problem of imbalance, especially falling backward. The flexed posture of PD, swallowing and speech difficulties, and situation-specific “freezing” are all challenges for improved drug therapy. Scientists have not yet determined where in the brain and what types of biochemical disturbance underlie these problems.
Death Rate From Parkinson’s Rising In Us Study Finds
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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:
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Fredric P. Manfredsson, Parkinson’s Disease Research Unit, Department of Neurobiology, Barrow Neurological Institute, Phoenix, Arizona, USA
No competing interests were disclosed.
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Tipu Z. Aziz, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
No competing interests were disclosed.
Patients Should Seek A Medication Review At Least Annually
There have been several exciting recent developments in the realization of advanced treatment options and new medications for Parkinsons disease. From surgical treatments to drug development to a pump that infuses medication to patients throughout the day, individuals with Parkinsons disease may benefit from the latest developments for treatment of PD.
Most patients with Parkinsons disease can be adequately treated the first several years after the disease has begun presenting symptoms with medications that deliver levodopa, used alone or in combination with carbidopa. Later in the disease, individuals with PD may consider highly effective surgical treatments such as Deep Brain Stimulation and/or other medications or combinations of medications to manage their symptoms.
Trey Eskew, a physicians assistant who has treated patients at Neurology Solutions Movement Disorders for the past six years, said that many patients arent aware of the new PD medications that have become available, including several that were released in 2015.
Here are some facts and findings about the latest PD medications.
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Side Effects Talk To Your Doctor Or Pharmacist
Like any medicines, Parkinson’s medicines can give you side effects. If you get side effects from your Parkinson’s medicines, tell your doctor or pharmacist. Common side effects include nausea , light-headedness, leg swelling and sleep problems. Also let them know if you think your medicines are causing confusion, hallucinations or involuntary movements. Some people have an unusual desire to gamble or engage in other obsessive behaviours. Tell your doctor if you experience any side effects, they may adjust the amount of medicine you take or you may be given another type. It is important that you don’t stop taking your Parkinsons medicines until you are advised to do so.
What Is Parkinsons Disease
Parkinsons disease is a progressive brain disorder that causes shaking and muscle stiffness, and slows movement. It develops when neurons in a particular part of the brain stop working properly and are lost over time. These neurons produce an important chemical called dopamine. Dopamine is used by the brain to send messages across brain areas to help control movement. Eventually, the brain cannot make enough dopamine to control the movement properly.1,2
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Levodopa: The Most Effective Drug For Treating Parkinsons
Levodopa, also known as L-DOPA, has long been, and continues to be, the most effective drug in treating Parkinsons disease symptoms. Most people with Parkinsons disease will take this drug at some point. There are side effects that can occur with Levodopa including nausea, fatigue and orthostatic hypotension. Often these side effects can be successfully treated so that Levodopa can be tolerated better. In addition, as the disease progresses and the brain has less ability to produce and process dopamine, dyskinesias, or involuntary movements can develop from Levodopa.
New Treatment Offers Improved Quality Of Life
Duopa has proven capable of addressing those problems.
A gel form of levodopa and carbidopa developed by AbbVie Inc., Duopa is delivered by an external pump directly into the small intestine through a surgically placed tube. The Parkinsons patient wears a small pouch that holds the pump and a drug cartridge. The Duopa is delivered continuously at a consistent level for up to 16 hours according to a schedule programmed into the pump.
Siddiqui said he monitored the efficacy of the drug and delivery system in Europe, where it has been in use under the name Duodopa since 2004. He directed the clinical trial of Duopa at Wake Forest Baptist as part of the multi-center study which led to its approval by the federal Food and Drug Administration in 2015.
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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 internus. 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 poorly. 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 tremor. 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 effects.
Traditional Treatment Of Parkinsons Disease
The levodopa in pills is absorbed in the blood from the small intestine and travels through the bloodstream to the brain, where it is converted into dopamine and stored in neurons.
In the initial stages of Parkinsons, the brain still has some neurons capable of producing and storing dopamine. The levodopa pills which usually contain a drug called carbidopa to reduce nausea and other side effects give the brain a boost to ensure a sufficient supply of dopamine, thus promoting normal motor control.
But during the diseases more advanced stages, there arent enough neurons left to produce or store enough dopamine. As a result, patients must take more and more levodopa pills in order to supply the brain with adequate levels. At the same time, Parkinsons causes stomach functions to become slow and unpredictable, which can delay or even prevent the medicine in the pills from leaving the stomach and reaching the bloodstream in the small intestine. Consequently, later-stage Parkinsons patients are subject to more frequent and more pronounced motor fluctuations.
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