University of Maryland Medicine Tests Novel Treatment for Parkinson's

Sept. 2,2015

Metabolic Imaging Center Uses New Ultrasound Technology to Target Deep Structures of the Brain

University of Maryland Medicine (the University of Maryland Medical Center and the University of Maryland School of Medicine) and its Center for Metabolic Imaging and Image-Guided Therapeutics (CMIT) has begun to use MRI-guided focused ultrasound on a deep structure within the brain related to Parkinson’s disease – the globus pallidus. 

In the first clinical trial of its kind, researchers from the Departments of Diagnostic Radiology & Nuclear Medicine, Neurosurgery and Neurology at CMIT are using magnetic resonance imaging (MRI) to guide ultrasound waves through the intact skin and skull to the globus pallidus. The University of Maryland is one of only two sites in the United States to offer this treatment to Parkinson’s patients. 

The globus pallidus contributes to the regulation of voluntary movements and is targeted with medications and, in advanced cases, deep brain stimulation using implanted micro-electrodes to treat motor symptoms of tremor, rigidity and dyskinesia in patients with Parkinson’s. Dyskinesia (abnormal, distorted movement) is a common side effect of the medication levodopa that can affect quality of life for patients with Parkinson’s. 

“In collaboration with my colleagues, we are excited to offer our patients a new, non-invasive therapy to control their Parkinson’s symptoms,” said principal investigator Howard M. Eisenberg, MD, the Raymond K. Thompson Chair of Neurosurgery. “The neurology community has made significant strides in helping patients with Parkinson’s over the years; utilization of MRI-guided focused ultrasound could help limit the life-altering side effects like dyskinesia to make the disease more manageable and less debilitating.” 

CMIT, under the direction of Rao Gullapalli, PhD, MBA, Professor of Diagnostic Radiology & Nuclear Medicine, is a collaborative venture between University of Maryland Medicine and industry partners, with the goal to explore, promote, innovate and create imaging technologies for efficient translation from “bench to bedside” and, ultimately, to serve as an inter-disciplinary “hub” of collaboration and innovation for engineering, physical sciences and medicine. The Medical Director for CMIT is Dheeraj Gandhi, MBBS, Professor of Diagnostic Radiology & Nuclear Medicine. 

“For years, our medical techniques have centered around anatomic imaging of the body and open surgical techniques to repair structural problems,” said Graeme Woodworth, MD, Associate Professor of Neurosurgery and Director of the Neurosurgery Department’s Translational Research Laboratory. “CMIT is set to move this paradigm toward imaging body function and modifying alterations using non-invasive, image-guided focused ultrasound technology. We are very excited that these new technologies, available at the University of Maryland, are on course to revolutionize medical diagnosis and treatment,” he said. 

According to Dr. Woodworth, examples of this work leverage altered metabolic pathways to visualize disease processes and treatment responses, providing new information regarding the course of a patient's condition. Using advanced focused ultrasound technology, surgeons can now apply microscopic sound waves to precisely target diseased regions deep within the body without incisions or radiation. 

Functional imaging and non-invasive ultrasound procedures are done on an outpatient basis in the CMIT MRI suite. During the Parkinson’s procedure, patients lie in an MRI scanner with a head-immobilizing frame fitted with a transducer helmet. Ultrasonic energy is targeted through the skull to the globus pallidus of the brain, and images acquired during the procedure give physicians a real-time map of the area being treated. 

“We’re raising the temperature in a very restricted area of the brain to destroy tissue,” Dr. Eisenberg said. “The ultrasound waves create a heat lesion that we can monitor through MRI.” 

The entire procedure lasts two to four hours, and patients are awake and able to interact with the treatment team. This allows the physicians to monitor the immediate effects of treatment and make adjustments if necessary. 

“Treatment-related side effects such as dyskinesia are the main reason my patients undergo surgery,” added Paul S. Fishman, MD, PhD, Professor of Neurology and sub-investigator on the clinical trial. “Focused ultrasound could offer these patients an alternative to surgery.” 

The clinical study builds on experience gained during a pilot trial that investigated focused ultrasound for patients with essential tremor. The University of Maryland Medical Center (UMMC) was one of eight sites that participated in the pivotal Phase III trial to support a submission to the FDA for regulatory approval, says site principal investigator Elias R. Melhem, MD, Professor and the Dean John M. Dennis Chairman of the Department of Diagnostic Radiology & Nuclear Medicine. The study continues to enroll patients at UMMC. 

“The University of Maryland Parkinson's Disease and Movement Disorders Center has long offered patients access to groundbreaking experimental therapies for Parkinson’s,” said E. Albert Reece, MD, PhD, MBA, Vice President for Medical Affairs at the University of Maryland and the John Z. and Akiko K. Bowers Distinguished Professor and Dean of the School of Medicine. “Our faculty's commitment to finding new treatment options for Parkinson’s patients shows the value of inter-disciplinary work that has potential for treating other critical neorogenerative diseases as well.” 

As many as one million Americans have Parkinson’s disease, a chronic, degenerative disorder for which there is no cure. The second most common movement disorder, Parkinson’s results from the malfunction or loss of brain cells crucial for movement and coordination. Symptoms include motor difficulties such as tremor, rigidity and postural instability. People with Parkinson’s can also experience non-motor symptoms of cognitive impairment, depression and anxiety, and autonomic dysfunction. 

Essential tremor, which is eight times more common than Parkinson’s disease, causes debilitating shaking that can be resistant to drug therapy. It mainly affects the hands, head and voice, making aspects of daily life like eating, drinking and writing extremely difficult. 

Researchers from the University of Virginia Health System reported in the New England Journal of Medicine in 2013 that 15 patients with essential tremor who received focused ultrasound saw “significant improvement” in their dominant hand tremor. Patients treated in the initial phase of the study at the University of Maryland experienced similar results. 

The Michael J. Fox Foundation for Parkinson’s Research and the Focused Ultrasound Foundation are funding the Parkinson’s study. It is being conducted using the ExAblate Neuro system developed by INSIGHTEC. Dr. Eisenberg is a consultant to INSIGHTEC.

GO to this link:

http://www.nbcwashington.com/news/health/324011971.html

About the University of Maryland School of Medicine

The University of Maryland School of Medicine, chartered in 1807 as the first public medical school in the United States, continues today as a leader in accelerating innovation and discovery in medicine. The School of Medicine is the founding school of the University of Maryland, and is an integral part of the 11-campus University System of Maryland. Located on the University of Maryland’s Baltimore campus, the School of Medicine works closely with the University of Maryland Medical Center and Medical System to provide a research-intensive, academic and clinically based education. With 43 academic departments, centers and institutes and a faculty of more than 3,000 physicians and research scientists, plus more than $400 million in extramural funding, the School is regarded as one of the leading biomedical research institutions in the U.S., with top-tier faculty and programs in vaccine development, cancer, brain science, surgery and transplantation, trauma and emergency medicine, and human genomics, among other centers of excellence. The School is not only concerned with the health of the citizens of Maryland and the U.S., but also has a global presence, with research and treatment facilities in more than 35 countries around the world. For more information, visit www.medschool.umaryland.edu.

About the University of Maryland Medical Center

The University of Maryland Medical Center (UMMC) is comprised of two hospitals in Baltimore: an 800-bed teaching hospital — the flagship institution of the 12-hospital University of Maryland Medical System (UMMS) — and a 200-bed community teaching hospital, UMMC Midtown Campus. UMMC is a national and regional referral center for trauma, cancer care, neurocare, cardiac care, diabetes and endocrinology, women's and children's health, and has one of the largest solid organ transplant programs in the country. All physicians on staff at the flagship hospital are faculty physicians of the University of Maryland School of Medicine. At UMMC Midtown Campus, faculty physicians work alongside community physicians to provide patients with the highest quality care. UMMC Midtown Campus was founded in 1881 and is located one mile away from the University Campus hospital. For more information, visit www.umm.edu.

http://health.einnews.com/article/284380005/CH3wYJ9kzGmMh4XC

Preventing and Treating Psychosis Post Anesthesia in PD: By Dr. De Leon

SEPTEMBER 2, 2015 ~ DEFEATPARKINSONS

I have heard of many patients being afraid to have procedures of any kind due to occurrence of psychosis and confusion reported by a number of Parkinson’s patients. This problem is not a myth unfortunately. Forty percent of Parkinson’s patients suffer psychosis commonly as disease advances which usually results in more hospitalizations, and increased procedures resulting in a greater need for anesthesia. Thus perpetuating the cycle. However, in my professional experience the majority of these episodes (psychosis post anesthesia) can be avoided by taking a proactive approach.

If surgery is required one must have evaluation of ones Parkinson’s symptoms for severity along with a complete evaluation of your medical regimen and a mini mental status exam prior to surgical procedure. The mini-mental status exam is KEY!!! The latter is particularly important in the face of long standing PD or advanced aged. This combination presents the highest risk for psychosis and delirium which is unfortunately often overlooked by most surgeons. I often would get consulted on other patients after the fact when a patient was psychotic and it never really was a surprised to me only to family and to rest of medical staff! This is true because if they would have bothered doing a full neurologic exam which included a mini mental status – they would have found cognitive deficits already present over 95% of the time prior to surgical procedures. In my patients I always stressed discussing with me prior to any and ALL procedures small or large especially if routine! This way I could have time to discuss with surgeons plan of action ahead of time and be involved in care. This is not always feasible in emergency cases but my patients and their families always knew to have their doctors put in a consult for me to manage their PD during their surgical procedures if hospitalized and receiving general anesthesia. One thing that everyone involved in care of Parkinson’s patients need to be aware of is that –Yes! PD patients represent a management challenge and need extra attention to have the best outcome.

Some of the common reasons people get psychotic with anesthesia:

• Underlying dementia (often times undiagnosed- in my experience this is the number one reason)
• Advancing age
• Interaction of PD meds with anesthesia e.g. Mao inhibitors
• Pain medication effect in light of PD meds and underlying dementia
• Poor swallowing leading to pneumonia/ atelectasis
• Decrease respiration /acid aspiration
• Urine infections
• Dehydration

Things to look at before any surgical procedure:

Preoperative continuation of levodopa

Aspiration prophylaxis Interaction of drugs with PD medications patients are taking

Duration of PD and systems disrupted –i.e. how is their cardiac function, their kidney function, their gastrointestinal function, their cognition, etc.

Surgical procedure – is it elective or emergent

Will hospitalization be required?

Type of anesthesia to be used-general vs. local

Will patient need to be bed bound – thus increasing DVT’s (clots) and also worsening PD symptoms like rigidity

First things we have to know about anesthesia:

1) Avoid halothane with levodopa if possible due to an increase in cardiac arrhythmia.

2) Use of Sympathomimetics  with Mao will increase BP- therefore need to suspend things like Azilect, and Eldepryl for up to a week before surgery. At same time recommend increasing other PD meds to compensate for that reduction so that you are the strongest prior to surgery.

3) Mao meds also inhibit metabolism of narcotics therefore narcotic effect can lasts longer in your system after surgery causing greater side effects- so may not want to resume Mao inhibitors right away after surgery if taking pain meds.

4) In advance PD sudden withdrawal of levodopa can be fatal at times causing neuroleptic syndrome. Therefore never recommend stopping this medication always look to take orally dissolvable Sinemet (levodopa/carbidopa) like Parcopa if have to be NPO (nothing by mouth).

5) Keep in mind that often times General anesthesia can relax muscles so much it can delay diagnosis of exacerbation by masking early symptoms.

6) PD patients who undergo general anesthesia have a tendency for increase chest infection due to ineffective cough mechanism and clearing of secretions and poor swallowing.

7) After general anesthesia these is increased nausea and vomiting meds often prescribed for this problem as well as those used with and during anesthesia can worsen PD symptoms.

My recommendations to prevent these common problems with general anesthesia:

Pre -operative care:

I am of the belief that patients should take medications up to the time of surgery by substituting things to bypass the GI system using oral disintegrating tabs such as Parcopa use dopamine agonist patches if necessary and discontinue Mao inhibitors- but increase dose by adding more dopamine after surgery to be able to deal with stress of body.

Don’t forget to evaluate for cognitive status and place on medications to protect many IV/IM/orally disintegrating meds and even patches ( Exelon, Abilify, Geodon, Zyprexa)

Take small sips of liquid if need be to get meds down to avoid exacerbation of symptoms.

If sedation is required Benadryl maybe be best solution because there is an IV form and helps with PD symptoms as well; works great for procedures of the eye.

Also ask for scopolamine patch – this decreases nausea and vomiting due to anesthesia.

Ask for reflux prophylaxis –such as Pepcid IV prior to surgery to avoid reflux and aspiration.

Peri- operative/intra-operative:

If at all possible get local anesthesia or nerve Block to avoid cognitive side effects as well as gi symptoms. Post- operative: Resumption of meds as soon as surgery over is very important. Because timing is so crucial medication schedule must be adhered to pre-intra, and post operatively. After surgery, broad time schedules of medication intake should be avoided completely! Staff MUST be instructed to stick to specific dosing times and not to deviate for more than 15 minutes (max) otherwise this can lead to erratic behavior and severe symptom breakthrough such as increased pain, depression, anxiety, confusion etc.

If unable to swallow post -surgery consider – nasogastric tube to give meds if needed if unable to get oral dissolvable or tolerate patch, etc.

Give water through feeding tube but also make sure getting fluids to prevent dehydration and getting IV antibiotics post -surgery.

Sometimes patients have difficulty voiding post operatively due to spasms of bladder- I recommend baclofen or macrodantin (nitrofurantuon).

If at all possible try to limit narcotics and use instead Tylenol #3, Toradol IV/PO/Vicodin only as needed. Trust me this works best if we follow all these steps are followed and all involved take a proactive role in the care of the PD patient. Of importance is also a temporary increase in PD medication doses during recovery/convalescing period.

Don’t forget to get ancillary consults like OT, PT, ST, and respiratory to provide breathing treatments and an incentive spirometer to prevent pneumonia. A team effort is the way to ensure a much less chance of having psychosis with anesthesia.

Don’t forget to include your neurologists/MDS for a best outcome and decrease post-surgery psychosis.

Sources:

http://www.bcmj.org/article/management-medical-and-surgical-problems-parkinsons-disease

http://practicalneurology.com/2014/10/inpatient-management-of-parkinsons-disease

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3141145/

http://defeatparkinsons.com/2015/09/02/preventing-and-treating-psychosis-post-anesthesia-in-pd-by-dr-de-leon-3/

Elevated mitochondrial bioenergetics and axonal arborization size are key contributors to the vulnerability of dopamine neurons

Dopamine-Neurons' High Energy Requirements Leads to Neuronal Overheating in Parkinson’s Disease

Aug. 31,2015

In a new study entitled “Elevated mitochondrial bioenergetics and axonal arborization size are key contributors to the vulnerability of dopamine neurons” scientists discovered why dopamine producing neurons are particularly vulnerable in Parkinson’s disease. These new findings point towards a key role for mitochondria and these neurons’ high energy requirements as the underlying disease triggering mechanisms. The study was published in the journal Current Biology.

Parkinson’s disease is a chronic progressive neurodegenerative disorder characterized by the loss of neurons in specific brain regions – the region called substantia nigra compacta, the locus ceruleus and the dorsal nucleus of the vagus nerve. Notably, however, while in Alzheimer’s disease a wide range of neurons are lost, in Parkinson’s disease only a small subset of dopaminergic-neurons (a class of neurons that produce the neurotransmitter dopamine) are affected. The mechanisms underlying this specificity are currently unknown but impaired mitochondrial function and pathological protein aggregation have been suggested to play key roles in Parkinson’s pathogenesis.

In this study, a team of researchers hypothesized that dopaminergic-neurons’ particular vulnerability could be attributed to their high-energy demands. As such, mitochondria could play an essential role as these organelles are cell’s “power-house”, which means they are responsible for generating energy and, in the case of neurons, allow the release of electrical signals and chemical messengers such as dopamine.

The authors showed that dopaminergic-neurons have a complex structure exhibiting a high number of extensions and neurotransmitter release sites, similar to a tree with multiple branches. The team discovered that it is this complex arborization of neuronal axons (axons are the long, slender projection of neurons, that typically conduct electrical impulses away from the cell body) that requires a high number of mitochondria to work very hard, leading neurons to “overheat”. This need for high-energy rates ultimately results in more susceptible neurons and may cause them to die.

These findings highlight that the bioenergetic and morphological specificities of substantia nigra dopaminergic-neurons underlies their increased vulnerability in Parkinson’s disease.

Louis-Éric Trudeau, a professor at the university’s Departments of Phamacology and Neurosciences, at Montreal University, Canada and study lead author commented, “Our work supports the theory that very complex neurons like those found in the substantia nigra force the mitochondria to constantly work at burnout rates to produce energy. This would explain the accelerated cell deterioration. To use the analogy of a motor, a car that overheats will burn significantly more fuel, and, not surprisingly, end up at the garage more often.” The study also contributed to advance the way scientists study Parkinson’s disease, as Trudeau noted, “For some unknown reason, it has been incredibly difficult to reproduce the symptoms of Parkinson’s in mice, even when introducing in the genome of these animals the same mutations found in humans afflicted by familial forms of the disease. Our discovery provides a new lead to potentially overcome such difficulties.”

http://parkinsonsnewstoday.com/2015/08/31/dopamine-neurons-high-energy-requirements-leads-neuronal-overheating-parkinsons-disease/

New Insights into Parkinson’s Disease and Synaptic Plasticity

Aug. 31, 2015

Researchers at Università degli Studi di Perugia and Ospedale Santa Maria della Misericordia in Italy recently published an article entitled “The changing tree in Parkinson’s disease” in the journal Nature Neuroscience. This report focused on recent findings, entitled “Dynamic rewiring of neural circuits in the motor cortex in mouse models of Parkinson’s disease”, published in the same journal by researchers at Huazhong University of Science and Technology in China and Stanford University School of Medicine in the United States.

Parkinson’s disease is a progressive neurodegenerative disorder that develops gradually, with patients usually experiencing the first symptoms around the age of 60 or older. As the disease progresses, the symptoms worsen from a barely noticeable tremor in the hands to serious difficulties in speaking, locomotion, coordination and balance. The disease is caused by the loss of the neurotransmitter dopamine due to premature death of dopaminergic neurons in the brain, which play an important role in voluntary movement and behavioral processes (mood, stress, reward, addiction). It is estimated that up to 10 million people worldwide suffer from the disease, and there is currently no cure for Parkinson’s or therapies able to halt or slow disease progression.

Parkinson’s disease patients suffer a decline in the neuronal ability to express synaptic plasticity, which is critical for learning and maintaining new motor skills and conserve memory throughout life. It is however not clear how the dopamine loss in these patients leads to a disruption in motor complex plasticity.

According to the authors, researchers used Parkinson’s disease mice models and a transcranial two-photon laser imaging technique to demonstrate that dopamine loss induces structural changes in the motor cortex.

Researchers analyzed the temporal evolution of neurons in the motor complex of Parkinson’s disease mice models and found a marked increase in both spine elimination and formation. Interestingly, the two main dopamine receptors were found to play different roles, with the D1 receptor regulating spine elimination and the D2 receptor controlling spine formation. These observations led the team to suggest that Parkinson’s disease may lead to an abnormal spine turnover instead of a major change in the absolute spine number of the motor cortex as previously thought.

Apart from the abnormal alterations in structural plasticity, changes in functional dynamics were also found, which ultimately lead to a decreased survival of newly formed spines (linked to both motor learning and memory maintenance) in the motor cortex. Together, the defective changes in functional and structural synaptic plasticity impairs learning mechanisms, motor performance and memory retention.

The authors concluded that this recent study revealed a novel dynamic rewiring of the neuronal circuits in the motor cortex of mice models of Parkinson’s disease, and suggests a disease model where the stabilization of newly formed learning-induced spines is defective, leading to a destabilization of neural motor circuits ultimately resulting in motor learning and memory deficits in mice, similar to what is observed in Parkinson’s patients.

The authors emphasize that Parkinson’s disease is not only linked to dopamine loss, and that a multisystem neurodegeneration actually characterizes the disease where other neurotransmitters are also involved, including serotonin, acetylcholine and noradrenaline which, all together, may influence both structural and functional plasticity.

http://parkinsonsnewstoday.com/2015/08/28/new-insights-parkinsons-disease-synaptic-plasticity/

Doctors Unravel The Placebo Effect Of Fake Parkinson's Disease Treatment

Doctors want to understand why some patients respond to
treatments they aren't even actually given.

Ben Wolford 

Posted with permission from Medical Daily                                               

Photo courtesy of Shutterstock.

Aug.31,2015

In a new study examining patients with advanced Parkinson's disease, neurologists say they've identified parts of the brain that control placebo effect, raising hopes of singling out people most susceptible.

But they're still very much in the dark about underlying causes of one of medicine's great mysteries. Some people, when given fake treatment, actually get better, but others, for whatever reason, do not. Stranger still, some people improve at the mere suggestion of future treatment.

The placebo effect is a problem for clinical researchers because they need to know which treatments work and which don't. When people respond well to treatments they aren't actually given or that don't actually work, it skews the results. That's why, for years, doctors have been trying to figure out how placebo works and why.

"While they may appear to be mysterious, placebo responses have discernible neurophysiological mechanisms," wrote the authors of a companion commentary in The Journal of Clinical Investigation. To learn more about those mechanisms, neuroscientists at the Feinstein Institute for Medical Research in New York chose 45 patients with Parkinson's disease for a double-blind study. All of them would receive brain surgery, but only 22 would receive actual treatment. The other 23 were given fairly routine operations designed to do nothing.

The doctors weren't looking for signs of placebo effect — they already knew it would happen. Patients with Parkinson's disease, the second most common neurological illness behind Alzheimer's, have previously shown an incredible sensitivity to the idea of treatment. A 2001 study illustrated that dopamine released at the expectation of possible healing had healing benefits by itself. "Expectations," doctors wrote in another study, "have a strong influence on 

the subsequent emotional experience of both" pain relief and reward processing.

Instead, what David Eidelberg and colleagues at the Feinstein Institute were looking for was what happened inside their brains before and after the brain surgery. Using PET scans, they measured activity in parts of the brain associated with negative emotions, expectancy and placebo-induced anti-depressive effects. After the placebo surgery, 16 of the 23 patients performed better on tests of their motor functioning. Seven saw no improvement.

Here's the interesting thing: Those 16 patients had very little activity before surgery in the parts of the brain that are activated by placebo. The other seven had more activity in the region all along. So that's the good thing — research doctors may now have something to look for when they want to weed out placebo-receptive test patients.

The bad thing is researchers still have no clue how a little dopamine and anti-depressant brain activity relates to improved motor function. "The final effector pathway remains obscure," wrote Mariya V. Cherkasova and A. Jon Stoessl in their commentary. But they say one thing is more clear from the study — expectation didn't have anything to do with it. The knowledge of participation in clinical trials did not induce placebo effect.

In a sad coda to the study, one year after their placebo brain surgeries, the Parkinson's patients were unblinded. That is, their doctors revealed that they had been in the sham surgery group and not the treatment group. Immediately, the parts of their brains that are activated by placebo reverted to their normal state. With that, their small gains in motor functioning disappeared, too.

Source: J.H. Ko, et al. Network Modulation Following Sham Surgery in Parkinson's Disease. The Journal of Clinical Investigation. 2014.

http://world.einnews.com/article/283878183/QcsEXdRCOdLFVJ0U

Inosine Trial Secures Phase III Funding to Study Effect on Slowing Parkinson’s

FoxFeed Blog

September 01, 2015


The Michael J. Fox Foundation’s largest grant to a single investigator thus far awarded $5.6M in 2008 to Michael Schwarzschild, PhD, of Massachusetts General Hospital for a Phase II trial of inosine, a precursor to the antioxidant of urate. Observational studies had shown people with higher levels of urate had lower risk of Parkinson’s disease (PD) and, if diagnosed with PD, slower disease progression.

Today Dr. Schwarzschild and his Parkinson Study Group colleagues announced funding from the National Institutes of Health (NIH) to conduct an inosine Phase III trial at 60 U.S. clinical sites with 270 people with early-stage Parkinson’s. Enrollment is expected to begin early next year.

One quick, very important note: Inosine is available commercially as a dietary supplement, but patients should act with caution. Inosine has not been proven as a therapy for Parkinson’s, and, in the absence of medical supervision, it can cause serious side effects such as gout, kidney stones and possibly high blood pressure. It is critical to discuss any medications or natural supplements with your physician before taking them.

MJFF Support Advances Potential Disease-Modifying Drug

"The Foundation's early and step-wise investment has not only helped us reach this advanced stage of testing for disease modification. The knowledge gained with its support also greatly enhances the prospects for success of the Phase III trial,” said Dr. Schwarzschild. "In addition to granting dollars to advance inosine's therapeutic candidacy, the Foundation has also provided valuable scientific, recruitment and regulatory guidance." 

The MJFF-funded Phase II study showed that inosine is safe, tolerable and does raise urate levels in people with early-stage PD.

The Foundation also funded early pre-clinical work investigating the mechanism of urate in neuroprotection. And MJFF will continue to support this project by funding two small studies — one clinical, one pre-clinical — to assess interactions between inosine and common foods and other medications taken by people with Parkinson’s.

“Patients’ greatest unmet need is a therapy to stop or slow Parkinson’s disease,” said Todd Sherer, PhD, MJFF CEO. “There is a large body of evidence to show that using inosine to raise urate levels could impact Parkinson’s progression. We’re glad that The Michael J. Fox Foundation could support this important work at a critical stage and that the NIH is funding this trial to move inosine closer to patient relevance.”

Because inosine is already commercially available, Foundation and government funding is essential for testing its efficacy as a Parkinson’s treatment. Pharmaceutical companies are not incentivized to invest in testing of a compound already on the market.

Scientists Uncover Potential Mechanism of Neuroprotection

Researchers have studied antioxidants, such as Vitamin E, for their effect on Parkinson’s disease before without success. A new paper from Dr. Schwarzschild’s team (from non-MJFF funded research), however, points to a urate-specific role in neuroprotection. This finding grows the evidence for likely disease modification with inosine. 

The investigators report that urate stimulates brain cells called astrocytes, the first step in a chain reaction releasing another antioxidant and activating a protein pathway. Both may protect brain cells from degeneration.

“This new evidence of a more nuanced molecular mechanism for urate-induced neuroprotection boosts our enthusiasm that this will be a truly novel strategy and not ‘just another direct antioxidant’ that will fail to protect the brain cells that degenerate in Parkinson’s,” said Dr. Schwarzschild.

Listen to Dr. Schwarzschild explain his inosine research in an MJFF podcast.

https://www.michaeljfox.org/foundation/news-detail.php?inosine-trial-secures-phase-iii-funding-to-study-effect-on-slowing-parkinson&os_cid=fb-a30U00000004hgl&s_src=MJFFfb&s_subsrc=inosine_trial_news#prclt-eHo1kjBl