Component #2 A Neuroprotective Agent
Once a drug or a treatment has been determined to slow down the progression of Parkinsons, it will be necessary to protect the remaining cells and provide a nurturing environment for the third part of the cure .
Neuroprotection is the area of research that has had the most attention over the years. Drug companies have employed vast resources in this area in the hope of discovering a treatment which will work across conditions , and thus provide them with tremendous profits. Unfortunately, conditions of the brain have proven to be a lot more complicated than first perceived and cross-condition therapies seem unlikely as we move towards greater stratification and personalisation of disease and treatment, respectively.
But there has been the hint of a potential neuroprotective effect in one class of drugs for Parkinsons: GLP-1R agonists.
Neuroprotective approach: GLP-1R agonists
Exenatide is a glucagon like peptide-1 receptor agonist. This is a class of drug that has traditionally been used for treating diabetes, but has recently been repurposed for Parkinsons.
After multiple studies suggested neuroprotective properties in models of Parkinsons, a clinical trial program was intiated, and in 2017, a Phase II Exenatide trial reported the stablisation of Parkinsons motor features over the course of the 48 week trial .
Reduction in motor scores in Exenatide group. Source: Lancet
In late 2019, we saw the initiation of a Phase III clinical trial for .
The Motor Network In Parkinsons Disease And Dystonia: Mechanisms Of Therapy
open to eligible people ages 21-75
This is an exploratory pilot study to identify neural correlates of specific motor signs in Parkinsons disease and dystonia, using a novel totally implanted neural interface that senses brain activity as well as delivering therapeutic stimulation. Parkinsons disease and isolated dystonia patients will be implanted unilaterally or bilaterally with a totally internalized bidirectional neural interface, Medtronic Summit RC+S. This study includes three populations: ten PD patients undergoing deep brain stimulation in the subthalamic nucleus , ten PD patients with a globus pallidus target and five dystonia patients. All groups will test a variety of strategies for feedback-controlled deep brain stimulation, and all patients will undergo a blinded, small pilot clinical trial of closed-loop stimulation for thirty days.
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How Do I Know If I Am Eligible For Treatment
Your doctor is the best person to ask about this. He or she will be able to tell you if you are a suitable candidate. In general, people who cannot go into an MRI will not be able to go through the treatment this includes patients with metallic implants, patients who are claustrophobic and patients who are allergic to contrast agents a dye used during MR imaging, patients who are over 300 lbs and patients who are under 22 years of age.
- If you have any kind of metallic implants, such as pacemakers, neurostimulators, spine or bone fixation devices, total joints, metal clips, screws, etc., you may not be a candidate. Any metallic implants must be non-magnetic to prevent injury to the patient from the MRs strong magnetic field.
- If you are not generally healthy enough to withstand the treatment and lie still in the same position for approximately 3 hours, you may not be a suitable candidate for this treatment.
- If you have had a recent myocardial infarction or have congestive heart failure , unstable angina pectoris , or spinal conditions, are you should discuss these issues with your doctor.
- If you have extensive scarring on the scalp, you may not be a good candidate.
- If you have any tumors inside the skull, you may not be a good candidate.
- If you are on dialysis, you may not be a good candidate.
- If you have an active infection or severe hematological, neurological or other uncontrolled disease, you may not be a good candidate.
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Component #3 Some Form Of Restorative Therapy
Once the condition has been slowed/halted and a neuroprotective/nurturing environment is in place to protect the remaining cells , a curative treatment for Parkinsons will require replacing some of the cells that have been lost.
And until we have developed methods that can identify Parkinsons long before the motor features appear , some form of cell replacement therapy is required to introduce new cells to take up lost function.Cell transplantation currently represents the most straight forward method of cell replacement therapy.
Cell Transplantation
Traditionally, the cell transplantation procedure for Parkinsons has involved multiple injections of developing dopamine neurons being made into an area of the brain called the putamen . These multiple sites allow for the transplanted cells to produce dopamine in the entire extent of the putamen. And ideally, the cells should remain localised to the putamen, so that they are not producing dopamine in areas of the brain where it is not desired .
Targeting transplants into the putamen. Source: Intechopen
Transplanted dopamine neurons. Source: Sciencedirect
The transplanted cells take several years to develop into mature neurons after the transplantation surgery. This means that the actually benefits of the transplantation technique will not be apparent for some time . Once mature, however, it has also been demonstrated that these transplanted cells can produce dopamine.
I think we are done.
What Are The Benefits Of Focused Ultrasound
- It is non-invasive, with generally lower major risks than open surgery and a shorter recovery time
- It is carried out as a single treatment. Patients typically recover rapidly and quickly return to their usual daily activities
- Focused ultrasound frequently offers rapid improvement of symptoms.Other technologies such as Gamma Knife radiosurgery have a significant delay before clinical improvement is seen, and deep brain stimulation requires regular programming of the electrical device, and either frequent recharging or further surgery to replace the battery when it expires
- In contrast to stereotactic radiosurgery lesioning, focused ultrasound does not use radiation, thereby avoiding the side effects of radiotherapy.
- No anaesthetic is required, therefore patient with significant medical comorbidity are eligible for this treatment
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Fda Approval Clears Way For Incisionless Brain Surgery As An Effective Non
A non-invasive ultrasound treatment for Parkinson’s disease that was tested in a pivotal trial led by University of Maryland School of Medicine researchers is now more broadly available at the University of Maryland Medical Center . Recent FDA approval of a device used in the procedure effectively opens up access to focused ultrasound beyond clinical trial participation.
The device, called Exablate Neuro and manufactured by Insightec, was approved in late 2021 by the U.S. Food and Drug Administration to treat advanced Parkinson’s disease on one side of the brain. UMMC is one of only several sites in the Mid-Atlantic region with the capabilities and expertise to perform focused ultrasound for Parkinson’s disease and other movement disorders. The procedure requires a multi-disciplinary team, including a neurosurgeon, movement disorder neurologist, and neuroradiologist.
A New Era For Parkinson’s Disease Treatment
“A diagnosis of Parkinson’s disease no longer automatically portends a future of extremely limited physical capabilities. Thanks to the commitment of researchers like Dr. Eisenberg and Dr. Fishmanand clinical trial participants like Steve Squirestreatment has expanded to include non-invasive options that significantly reduce certain symptoms within minutes and transform the lives of people who had been living with debilitating symptoms,” said Bert W. O’Malley, MD, President and CEO of the University of Maryland Medical Center.
“Our school of medicine researchers have established themselves as world leaders in pioneering MRI-guided focused ultrasound for many devastating brain diseases, including Parkinson’s and essential tremors,” said E. Albert Reece, MD, PhD, MBA, Executive Vice President for Medical Affairs, UM Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor and Dean, University of Maryland School of Medicine. “The stellar work of Dr. Eisenberg and Dr. Fishman has led to a new era in which this breakthrough modality has now become the standard of care for patients looking for less invasive treatments for their symptoms.”
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Understanding Sleep Problems To Prevent Parkinsons
Brain scans of people who experience RBD show increased inflammation the bodys natural response to injury, coming from immune cells in the brain called microglia. Research suggests that excessive levels of inflammation in the brain may cause damage to brain cells and play a role in the progression of Parkinsons.
The involvement of immune cells in Parkinsons has peaked researchers interest in the possibility of dialling down inflammation in the brain. And there is ongoing work through the Parkinsons Virtual Biotech to find and develop potential anti-inflammatory drugs.
Project Galaxy is focusing on developing molecules that can get into the brain and target a specific protein on the surface of microglia that has been shown to be present at much higher levels in the brains of people with Parkinsons than in people without the condition. This could pave the way for a future treatment to slow or stop the progression of the condition.
Targeting inflammation at the earliest stages of Parkinsons may also be important when aiming to slow the loss of cells and delay the onset and progression of symptoms. While identifying Parkinsons early is challenging, doing so opens the door to treating the condition before symptoms become problematic and potentially even preventing people from developing Parkinsons.
Focused Ultrasound For Parkinsons Disease
Although elective procedures are currently being postponed in hospitals across the country because of the necessary focus on COVID-19, eventually our hospitals will return to normal and non-emergent procedures will be performed again. This will include elective procedures for the treatment of Parkinsons disease .
Two brain procedures that are approved for use in PD are deep brain stimulation and high intensity focused ultrasound . I encourage you to read more about DBS and view our webinar which outlines the newest features of this procedure.
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What Is The Treatment Process
The patient is positioned on the treatment bed in the MRI room with their head places in the Exablate Neuro helmet. Cool water is circulated around the scalp to avoid heating.
This is achieved with MRI-guided feedback of temperature changes at the target.
Treatment is generally unilateral, typically treating the dominant and/or most severely affected hand.
If you have additional questions, please email .
A Research Team Led By Yu
HSINCHU, TaiwanUltrasound is widely used for conducting physical examinations, and plans are underway for expanding its application to the treatment of Parkinsons disease, dementia, and diabetes. A research team at National Tsing Hua University led by Associate Professor Yu-Chun Lin of the Institute of Molecular Medicine and Professor Chih-kuang Yeh of the Department of Biomedical Engineering and Environmental Sciences has successfully improved the motor symptoms of Parkinsons disease in mice by injecting cellular proteins that are highly sensitive to ultrasound waves into the deep brain region and afterwards using ultrasound to activate the neuron cells.
Their innovative research has been published in the January issue of Nano Letters, and their non-invasive treatment has already been patented in Taiwan and the US.
Lin has long sought to find a safe, non-invasive way to control cell activity. Although light waves are safe, they can only penetrate to a depth of about 0.2 cm magnetic waves can penetrate deep, but lack precision. By contrast, ultrasonic waves penetrate to a depth of up to 15 cm, and can be focused on the affected part. Thus, the challenge was how to make cells respond to ultrasound.
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Low Intensity Focused Ultrasound To Help Deliver Therapies
While high intensity FUS is a treatment for PD as described above, low intensity FUS can be used in an entirely different way to help treat PD. This type of FUS may allow for disruption of the blood brain barrier. The blood brain barrier refers to the cells that line the blood vessels within the brain which keep foreign substances, such as toxins and microbes, in the bloodstream and out of the brain.
Normally, this mechanism is advantageous and protects the brain. However, the blood brain barrier may also keep out molecules that could help to treat brain diseases. Therefore, disrupting the blood brain barrier could allow for penetration of these molecules into particular areas of the brain. A whole variety of different molecules such as antibodies, nerve growth factors and gene therapy may be able to take advantage of this approach. Further research is necessary to determine if this will be a useful method for drug delivery into the brain.
Am I A Candidate For Mrgfus
MRgFUS is FDA approved for the treatment of patients with essential tremor and tremor-dominant Parkinson disease. It can only be used to treat one side of the brain even if tremor is present on both sides. MRgFUS is not yet FDA approved to treat both sides. If first line medications fail to adequately control your tremor, your doctor may consider recommending either MRgFUS, deep brain stimulation, or radiosurgical thalamotomy. Compared to other surgical treatments for essential tremor, no device implant is needed, no incision is required, and the treatment works immediately. To read more about What to Expect During Consultation for Essential Tremor, .
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How Do I Request An Initial Consultation
If you are suffering from Essential Tremor, Parkinsons disease or another type of tremor or movement disorder and would like to know whether you might be suitable for treatment with focused ultrasound, please request a consultation and our clinical care coordinator will contact you:
Alternatively, please email your referral or enquiry to
Our assessment process includes:
- Confirmation of your diagnosis and its impact on your quality of life.
- Other relevant medical condition and medications you are on.
- Brain scanning with MRI and CT
Our clinical assessment team includes a movement disorder neurologist and neurosurgeon.
Our clinical care coordinator will coordinate all aspects of your assessment from the time we receive your referral. If you have any questions, please contact us.
Expanded Indication Includes Medication
byJudy George, Senior Staff Writer, MedPage Today November 5, 2021
The FDA expanded the approval of Exablate Neuro focused ultrasound to treat advanced Parkinson’s disease patients with mobility, rigidity, or dyskinesia symptoms, device maker Insightec announced Wednesday.
With this new indication, Exablate Neuro is approved for unilateral pallidotomy in medication-refractory Parkinson’s patients with moderate to severe motor complications.
The device uses MRI-guided focused ultrasound waves to target and ablate the globus pallidus, requiring no incisions or brain implants. “Movement disorder neurologists now can offer their Parkinson’s patients a less invasive surgical option as part of their treatment plan,” said Paul Fishman, MD, PhD, of the University of Maryland, in a statement.
Exablate Neuro previously was approved to treat medication-refractory essential tremor and tremor-dominant Parkinson’s disease.
Early studies suggested that focused ultrasound subthalamotomy and pallidotomy performed on one side may reduce motor manifestations of Parkinson’s disease. A sham-controlled trial of patients with markedly asymmetric Parkinson’s disease found that focused ultrasound subthalamotomy performed in one hemisphere resulted in improved motor scores at 4 months, but was associated with adverse events including dyskinesias and other neurologic complications.
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Fda Approves Focused Ultrasound For Common Parkinsons Symptoms
UVA is one of only 37 medical centers in the country with the capacity to offer an incisionless form of brain surgery to treat advanced Parkinsons disease.
The U.S. Food and Drug Administration has approved an incisionless form of brain surgery to treat advanced Parkinsons disease after successful testing at the University of Virginia School of Medicine and other sites.
The authorization allows the use of Insightecs Exablate Neuro focused ultrasound device to treat problems with mobility, rigidity and involuntary movements, known as dyskinesias, that are common in Parkinsons. UVA is one of only 37 medical centers in the country with the capacity to offer this minimally invasive treatment, according to the Charlottesville-based Focused Ultrasound Foundation, a longtime supporter of UVAs pioneering research into the many potential applications of the technology.
Prior to the approval, available treatments for the Parkinsons symptoms included drugs, which not all patients respond to, and invasive deep-brain surgeries.
Dr. Jeff Elias is a pioneer in the field of focused ultrasound who led UVAs testing of the technology for treating Parkinsons.
How Are Parkinsons Disease And Essential Tremor Treated
Medication is the first choice for Parkinsons treatment, but Parkinsons patients dont respond well to drugs or have side effects. In Essential tremor, the response rate to medications is less than Parkinsons disease and up to 30% may not tolerate medications or may have an unsatisfactory response. In these cases, surgical treatment may be considered.Before the arrival of FUS, surgical options for Parkinsons treatment included thalamotomy and deep brain stimulation .Both these options are considered minimally invasive although they involve incisions, use of drills to open a small hole in the skull and the insertion of one or more electrodes into the brain. In the case of DBS, the hardware is implanted into the brain and a pacemaker similar to a heart pacemaker is implanted into the chest wall.
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