New Insight May Unveil Ways to Lessen Side Effects of Deep Brain Stimulation in Parkinson’s Patients

deep brain stimulation

Distinct connections between nerve cells in the brain may explain why some Parkinson’s disease patients develop impulsivity and behavioral problems after deep brain stimulation (DBS) therapy, according to a recent study.

These findings may help make DBS safer and more effective by adequately targeting the regions in the brain responsible for motor control.

The study, “The structural connectivity of subthalamic deep brain stimulation correlates with impulsivity in Parkinson’s,” was published in the journal Brain.

Subthalamic deep brain stimulation (STN-DBS) is a surgical treatment intended to ease Parkinson’s motor symptoms, including tremor rigidity and bradykinesia (slow movements). The procedure involves implanting a device that generates electrical impulses in specific regions of a patient’s brain.

Patients who receive DBS may also be able to reduce or stop taking dopaminergic therapies such as levodopa — a precursor to dopamine, the missing neurotransmitter in Parkinson’s disease.

But in some patients, DBS stimulates neuropsychiatric symptoms, most commonly impulsivity and mood elevation.

“Some patients develop new problems with controlling their impulses and behaving recklessly after this procedure, which can give rise to personal problems and increase the strain on their families,” Philip Mosley, PhD, the study’s lead author, said in a press release. “These impulse-control and behavioural problems limit the improvement in quality of life enjoyed by the majority of patients who undergo this procedure.”

Neuropsychiatrist Mosley and researchers at the QIMR Berghofer Medical Research Institute in Australia investigated which factors could be responsible for the association between DBS and impulsivity. They hypothesized that connectivity between neurons prior to therapy as well as how DBS stimulated certain brain regions could be important contributors.

“We wanted to find out if there was a subtle difference in the way stimulation was affecting the brains of those people who developed these psychiatric side-effects, and if by exploring these differences we might be able to work out how to stop it happening altogether,” Mosley said.

They analyzed a total of 55 patients with Parkinson’s disease, including 17 who had a history of impulse controlled-behaviors before the DBS procedure. These included gambling in 10 patients, hypersexuality in nine patients, compulsive shopping in three patients, deregulated levels of dopamine in two patients, binge eating in one patient, and hobbyism also in one patient.

Impulsivity was evaluated using a combination of neuropsychiatric tools and engagement in a gambling paradigm using a virtual casino.

All participants were assessed for impulsivity at the beginning of the study and then again three months after DBS surgery.

“We used a ‘virtual casino’ that we had previously developed, which simulated ‘real-world’ impulsivity, and looked at how the brain networks influenced by DBS affected gambling,” Mosley said. “Our participants played the casino before DBS and again once their stimulator was implanted and turned on, so we could quantify whether stimulation influenced them to bet in a more risky manner.”

Additionally, the team used different imaging techniques to map the connections between nerves that were being stimulated by DBS’ electrodes.

Overall, 17 participants developed clinical signs of impulsive behavior linked to DBS. Past or present impulse controlled-behaviors did not seem to be predictive of behavior changes after DBS.

Those who had a prior history of impulse controlled-behaviors “also did not differ in postoperative neuropsychiatric measures or gambling behaviours,” the researchers wrote.

Importantly, when DBS stimulated a part of the brain called the prefrontal cortex, participants were more likely to place higher and riskier bets.

“This region of the brain is important for planning behaviour and inhibiting inappropriate actions, so it makes sense that stimulation of this part of the brain can change behaviour in this way,” Mosley said.

The researchers also observed a significant association between behavioral changes after DBS and a strong connection between the stimulation site and a region of the prefrontal cortex known as the orbitofrontal cortex.

“This was a fascinating finding, because this region has been shown to be important in how the brain evaluates a desired goal and compares it to an actual outcome, in order to work out if behaviour should be modified,” Mosley said.

“It is possible that these individuals developed such significant problems because their brains weren’t able to perform this function, which meant that they didn’t link poor choices to negative outcomes, and therefore didn’t learn from the experience,” he said.

When the researchers evaluated the relation between motor symptoms and changes in behavior, results showed that impulsive patients were more likely to have worse motor symptoms after DBS and that “improvement in motor symptoms was associated with greater stimulation of the motor subregion of the STN.”

“Overall, these findings imply the existence of a connectivity target that could optimize motor symptoms whilst minimizing neuropsychiatric side effects,” and highlight the importance of accurately targeting brain regions for DBS stimulation, according to the study.

These findings may help surgeons and neurologists decide where to place DBS electrodes to maximize the therapy’s benefits, while lessening the risk of neuropsychiatric side effects.

“Specifically, knowing which connections are harmful or helpful will assist neurologists and neurosurgeons decide where best to place the DBS electrodes and how to adjust the device postoperatively so that only regions of the brain responsible for treating the motor symptoms of Parkinson’s disease are stimulated,” Mosley said.

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Rewiring the Brain: Taking a Fresh Look at Chronic Pain

exercise, chemical hazards, coping skills, frustration, relationships, things, what ifs, shut in, toilet paper, serenity, laughter

For 15 years, I have been a failure at managing my chronic pain. I was prescribed oxycodone with gabapentin, and after my Parkinson’s diagnosis, I was put on levodopa. This decreased my pain to the point where oxycodone was no longer needed.

I also tried alcohol and marijuana in a rigorous attempt to make the pain vanish, replacing it with “feel-goods.” I know that chasing after “feel-goods” is not the right approach for me, so I stopped all the pain medications except levodopa.

At this juncture, I wish to be clear that I am not recommending anyone stop their medications. This is my personal journey, and I made decisions in consultation with my healthcare providers. For me, the risk of opioid treatment far outweighed the benefits.

Gabapentin in my system dulled my brain to the point that my cognitive abilities (or lack thereof) adversely affected my quality of life. Only in the last few months have all the pieces finally fallen into place to reveal a fresh approach to chronic pain management.

Chronic pain management is not just about popping a pill and hoping to be pain-free. No matter what I do, I will always have chronic pain from Parkinson’s every day. The goal is to live better. Medications that seek to disguise this reality within the gaudy attire of society’s “feel-good” addictions always send up big, red warning flags for me.

The brain has a remarkable ability to rewire itself so it can function better, even with chronic pain. If I am putting chemicals in my brain or using a set of addictive thoughts or feelings that interfere with that rehabilitative rewiring, then I must change or give up. Giving up and showing up are just a breath and a step apart.

The Parkinson’s chronic pain management program I use incorporates many of these small changes to help me live better. Here is my list:

This list reflects some of the information available to the public on chronic pain management. Each small change supports a small increase in the space between chronic pain and the thought or feeling in reaction to that pain. Each small change strengthens the stability of the pause.

With a long enough pause, it is possible to call on the conductor, who can then reroute the brain’s response to pain and surges of exaggerated mood (SEM) attacks. Once the conductor is called upon, one can discover something more — a fresh new look at chronic pain management.

The old ways of coping with pain were not working because SEM attacks were causing an exaggeration of the pain signal and emotions. In our search to live better with this, we discovered a new exercise approach, and along the way, a few gems of wisdom, including:

  • Intense emotional experiences can exacerbate chronic pain.
  • Uncontrolled actions connected to intense emotional experiences can also increase pain.
  • Skilled meditators experience intense emotions differently than the average person.
  • People with highly skilled conductors will experience intense emotion differently. Seeing the intense emotional experiences, along with pain, from the viewpoint of the conductor is not the same as the original emotional/pain experience.
  • Marijuana used in a sacred way can help to hold open the viewing window for the conductor.

With patience and perseverance, I sat at the conductor’s viewing window every day for more than four months. Many of the discoveries from this view are chronicled in my columns.

Connected to SEM attacks is the idea of anxiety or sad emotion surges that are not tied to context. Many of the emotional surges were purely abnormal Parkinson’s biochemicals with no environmental or conscious antecedent — just a surge of emotion due to brain chemistry.

Given this to be true, and my history using a well-trained conductor, I passionately believed a new brain path would be found. At the time, I was just using the conductor’s window to find a way to tone down the SEM attacks. What I discovered was a lot more, and yet so simple.

The need to fight, flee, or act in a way to seek nurturing is an automatic, often instinctual response to pain signals. If those pain signals are exaggerated, the response can be, too. In my case, it is all based on illusion caused by an organic malfunction. There is no external threat that requires a fight/flight/nurture-seeking response. As Neo said in “The Matrix” sci-fi movie, “There is no spoon.”

This perception of the difference between a thought/feeling and an observed thought/feeling isn’t just an idea for me, but rather an experienced phenomenon connected to the vision of a better life. At the conductor’s window, I sat and watched the exaggerated illusionary signal, I watched the pain and emotions approach, and I saw them redirected down a new track leaving no consequence visible to others. I felt no fanfare, no bliss, no awe. Just a soft, everyday calmness and a sense that I can do this conductor rerouting.

In a prominent place in the home, I put up a calendar to document success. At the end of each day, I share with a family member the placing of a big, red check mark for every day the conductor successfully reroutes the reaction to pain and SEM attacks.


Note: Parkinson’s News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The opinions expressed in this column are not those of Parkinson’s News Today or its parent company, BioNews Services, and are intended to spark discussion about issues pertaining to Parkinson’s disease.

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Dosing Begins in Phase 1 Trial for PTC’s Experimental Parkinson’s Therapy PTC857

PTC857 Phase 1 trial

The first participant has been dosed in a Phase 1 clinical trial evaluating the safety of PTC857, PTC Therapeutics‘ investigational therapy for Parkinson’s disease.

In addition to safety, the trial, which is being conducted in healthy volunteers, will evaluate how the therapy affects and is processed by the body. If the study concludes that the treatment has a reasonable safety profile, the results will be used to inform further investigations in people with Parkinson’s.

Participants in the trial will receive either a single dose of PTC857 or they will get multiple ascending doses, in which the dosage increases each time.

“We are excited about the initiation of this study for PTC857, which was developed from our novel Bio-e platform,” Stuart W. Peltz, PhD, CEO of PTC Therapeutics, said in a press release.

The Bio-e platform uses biochemical knowledge to aid in the development of therapies that target oxidoreductases — a family of enzymes believed to play a central role in the diseases of the nervous system. PTC857 is the second compound developed through the Bio-e platform to enter clinical trials, the other being PTC743, which is being evaluated as a potential treatment for Frederich’s ataxia.

Both PTC857 and PTC743 work by targeting the same enzyme: 15-lipoxygenase. By targeting this enzyme, it is believed that these treatments could reduce inflammation in the brain. In addition, targeting 15-lipoxygenase could reduce oxidative stress — an overproduction of highly reactive compounds that can damage cell structures.

Since both inflammation and oxidative stress in the brain are thought to contribute to the development of neurological diseases, including Parkinson’s, reducing these processes by targeting 15-lipoxygenase with PTC857 could be therapeutic.

PTC857 is first being developed specifically as a treatment for people with Parkinson’s who have a mutation in the GBA gene, a subtype known as GBA Parkinson’s disease, which is one the most common genetic subtypes of Parkinson’s disease. According to PTC Therapeutics, the investigational therapy has shown promise in animal models of GBA Parkinson’s disease, as well as in models using cells in dishes.

“PTC857 is an inhibitor of the key enzyme whose products modulate fundamental pathways that are involved in neuroinflammation and oxidative stress that lead to multiple disorders including GBA Parkinson’s disease,” Peltz said. “We look forward to completing the healthy volunteer study and advancing PTC857 into patients.”

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Staying Safe in Summer’s Sunshine

soft voice, wish, fires, silent symptoms, marriage, tasks, bucket lists, forgetfulness

Summer is here in the U.S., bringing with it humidity and heat. So, in the midst of the stickiness, sweatiness, and eventually, the ripened smelliness, we might ask ourselves, “Should I stop drinking water and dehydrate myself so that I stop sweating, thereby skipping the stinking?”

Uh, not recommended. 

Dehydration adds to problems already in the brain of a person with Parkinson’s disease. Since we already have enough problems with our brains, why create more? 

When we are dehydrated, our brain cells don’t function properly, which leads to cognitive issues. Dehydration, even if slight, causes our brains to work harder at whatever mental or physical tasks we may find ourselves involved in.

Just last year, I experienced my first (and hopefully last) heatstroke. Thankfully, my neighbor is a nurse and recognized what was happening, and helped me out.

With the onslaught of summer’s heat, it’s important to follow some simple, healthy guidelines while basking or working in the summer sunshine.

It may seem elementary, but staying hydrated is the best way to stave off getting overheated, and water is the best choice for that. 

Adding a lemon or lime wedge to your water is helpful for those who don’t care for “plain” water or who have a hard time tolerating it. A lemon also can help you drink more water than you normally do because it tends to make you thirstier.

Wear light-colored and loose clothing when working out in the garden. Do your outside chores in the morning or in the evening when it is cooler.

Know the signs of heatstroke. According to the Mayo Clinic, they include a flushed face, high body temperature, headache, nausea, rapid pulse, dizziness, and confusion. 

You may not mind sweating or being sticky. You may not even mind being stinky. But becoming sickly because you allowed yourself to become dehydrated on a hot summer day isn’t worth the risk.


Note: Parkinson’s News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The opinions expressed in this column are not those of Parkinson’s News Today or its parent company, BioNews Services, and are intended to spark discussion about issues pertaining to Parkinson’s disease.

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Single Treatment Creates New Neurons, Eliminates Parkinson’s in Mice, Study Shows

restoring neurons

With a single treatment, scientists were able to transform brain cells into functioning neurons that restored dopamine — the signaling molecule deficient in people with Parkinson’s disease — to normal levels, eliminating motor symptoms in a Parkinson’s mouse model.

The results, “Reversing a model of Parkinson’s disease with in situ converted nigral neurons,” were published in the journal Nature

Parkinson’s disease is characterized by the malfunction or death of dopamine-producing nerve cells (neurons) in a region of the brain called the substantia nigra, which is responsible for muscle movement and coordination. 

While most therapeutic strategies aim to regulate dopamine levels, treat motor symptoms, or prevent the loss of neurons, a potential alternative is to replace the lost neurons. 

Recently, researchers at the University of California San Diego (UCSD) School of Medicine reprogramed fibroblasts — a cell in connective tissue that produces collagen — into neurons by blocking the production of a protein called PTB. 

PTB influences which genes are turned “on” or “off” and is naturally produced at low levels during the development of neurons. 

“This protein is present in a lot of cells,” study lead Xiang-Dong Fu, PhD, from UCSD, said in a press release. “But as neurons begin to develop from their precursors, it naturally disappears. What we’ve found is that forcing PTB to go away is the only signal a cell needs to turn on the genes needed to produce a neuron.” 

These findings prompted Fu and colleagues to wonder if this same strategy can be applied to reprogram brain cells into neurons to produce dopamine as a potential Parkinson’s treatment. 

To find out, the team focussed on brain cells known as astrocytes, which are abundant star-shaped, non-neuronal cells that provide physical support for neurons and help regulate the transmission of electrical impulses within the brain.

An antisense oligonucleotide (ASO) was used to block PTB production, which is a small molecule designed to bind to messenger RNA (mRNA) — molecules that carry the DNA message containing the information to make proteins. The ASO, called shPTB, binds to PTB mRNA, causing it to be degraded. 

First, depleting PTB in isolated mouse and human astrocyte cells converted them into functioning neurons. Then, applying this same strategy directly to mouse brains, using a harmless adeno-associated virus (AAV) delivery system, there was a progressive conversion of astrocytes to new dopamine producing neurons in the midbrains of the mice, the area most affected in Parkinson’s patients. 

Based on this success, the technique was applied to mice first treated with 6-OHDA, a chemical that is toxic to dopamine-producing neurons and triggers Parkinson’s disease-like symptoms. 

Compared to those treated with an empty AAV vector, about 30% of astrocytes in mice treated with the AAV-shPTB converted to dopamine-producing neurons that integrated into the dopamine pathway — and restored dopamine to the levels found in normal mice. 

Three experiments were conducted to test the ability of AAV-shPTB to restore motor function in mice treated with 6-OHDA. The first two involved treating mice with medication that cause them to walk in circles. Treatment with AAV-shPTB progressively restored behaviors of mice in both tests to nearly normal levels within three months. 

The final test examined spontaneous motor activity by observing how mice used their limbs. Normal mice used both limbs with equal frequency, whereas mice treated with 6-OHDA preferred using limbs on one side of the body. Following AAV-shPTB treatment, regular limb use improved over time, which demonstrated the “full correction of the motor phenotypes in this chemically induced model of Parkinson’s disease,” the researchers wrote. 

“I was stunned at what I saw,” said study co-author William Mobley, MD, PhD, professor at UCSD. “This whole new strategy for treating neurodegeneration gives hope that it may be possible to help even those with advanced disease.”

“It’s my dream to see this through to clinical trials, to test this approach as a treatment for Parkinson’s disease, but also many other diseases where neurons are lost, such as Alzheimer’s and Huntington’s diseases and stroke,” said Fu. “And dreaming even bigger — what if we could target PTB to correct defects in other parts of the brain, to treat things like inherited brain defects?”

“I intend to spend the rest of my career answering these questions,” he added.

The team now will focus on optimizing its methods and test the approach in genetically-induced Parkinson’s mouse models. 

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Deep Brain Stimulation Not Linked to Greater Risk of Dementia for Parkinson’s Patients, Study Concludes

deep brain stimulation

Long-term deep brain stimulation (DBS) is cognitively safe and does not increase the risk for dementia in people with Parkinson’s disease, according to the results of a 10-year follow up study.

However, being male, older, having hallucinations, scoring low on cognitive tests, and perioperative cerebral hemorrhage (bleeding in the brain that occurs during or after surgery) were identified as risk factors for developing dementia in Parkinson’s patients with longstanding DBS.

“These results are very encouraging for people with Parkinson’s and their families that they can take advantage of the benefits of deep brain stimulation without worrying about it increasing the likelihood of developing dementia,” Elena Moro, MD, the study’s lead author, said in a press release.

The study, “Dementia and subthalamic deep brain stimulation in Parkinson disease,” was published in the journal Neurology.

DBS is an invasive treatment option for patients with advanced Parkinson’s disease who do not respond well to conventional medication.

The technique involves implanting electrodes into specific areas of the brain to deliver electrical signals to ease motor symptoms. The amount of stimulation is controlled by a pacemaker-like device placed under the skin, normally at the upper chest.

For advanced Parkinson’s cases, DBS outperforms other therapeutic strategies, but it is not currently recommended for patients with moderate or severe cognitive impairment or dementia due to fears it will worsen a patient’s cognitive skills.

Data on this matter, however, is controversial, with some studies suggesting a negative impact of DBS on cognition, whereas other studies have reported the therapy has beneficial effects.

It remains unknown whether these different results are potentially linked to specific risk factors that may increase the risk of dementia after DBS for certain Parkinson’s patients.

Now, researchers at the Grenoble Alpes University, France, and colleagues performed a retrospective analysis of 175 Parkinson’s patients who underwent bilateral (both sides) subthalamic nucleus DBS (STN-DBS), between 1993 and 2007. The subthalamic nucleus is a part of the brain that is involved in motor and cognitive functions.

The team evaluated the incidence of dementia after DBS after one year (short-term), five years (medium-term) and 10 years (long-term). The presence of dementia was evaluated according to the Diagnostic Criteria for Dementia (DSM-V13) at each follow-up after DBS surgery.

Researchers also evaluated potential risk factors for postoperative dementia.

Of the 175 patients included in the analysis, all were evaluated one year after DBS, 142 (81.2%) after five-years, and 104 (59.4%) after 10 years. Fifty patients (28.6%) were lost after the 10 years of follow-up and 21 (12%) died.

At one-year follow-up, four out of the 175 patients developed dementia. This number increased to 12 after five years, and at 10 years, 31 of 104 patients had dementia. Overall, this corresponded to a prevalence of 2.3% at one year, 8.5% at five years, and 29.8% at 10 years.

After a median follow-up of six years, and when including patients lost to follow-up and those who died, the incidence of dementia was 2.3% (at one year), 10.9% ( five years) and 25.7% (10 years).

“These rates are not higher than those reported in the general population of people with Parkinson’s,” said Moro, who also is a fellow of the American Academy of Neurology. “The few studies that are available with similar disease duration have reported higher rates of dementia. Other studies of people with Parkinson’s who are taking medication for their symptoms show an incidence rate for dementia that varies from 50 to 100 per 1,000 person-years,” she said.

When comparing patients with and without dementia after 10 years of follow-up, researchers identified that being male, older, having hallucinations, lower cognitive scores prior to surgery, and perioperative cerebral hemorrhage were predictors of dementia.

“Knowing these predictors may help us to select people who would respond best to deep brain stimulation and who might have a greater risk of having a poor cognitive outcome,” said Moro.

Overall, these results suggest that “in patients with PD with longstanding STN-DBS, dementia prevalence and incidence are not higher than those reported in the general PD population,” the researchers wrote.

“Except for few patients with peri-operative cerebral hemorrhage, STN-DBS is cognitively safe, and does not provide dementia risk factors in addition to those reported for PD itself,” they concluded.

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Planned Phase 2 Trial of ANVS401, Targeting Toxic Proteins, Moving Forward

ANVS401 trial planned

A planned Phase 2 clinical trial evaluating ANVS401Annovis Bio‘s lead investigational therapy for people in the early stages of Alzheimer’s and Parkinson’s disease, has received approval from a central institutional review board (IRB).

An IRB is an administrative body responsible for protecting the rights and welfare of human research subjects participating in clinical trials. Among its duties, the IRB reviews a trial’s proposed design and purpose to ensure they are up to ethical standards.

“We are excited to receive IRB approval to move forward with this Phase 2 study in PD [Parkinson’s disease] and AD [Alzheimer’s disease],” Maria Maccecchini, PhD, the CEO of Annovis Bio, said in a press release. “We believe we remain on track to complete the study by the first quarter of 2021.”

Both Parkinson’s and Alzheimer’s are characterized by the pathological buildup of clumps of proteins in the brain — specifically, clumps of the protein alpha-synuclein in Parkinson’s, and of beta-amyloid and tau in Alzheimer’s. These  accumulations disrupt communication between nerve cells and eventually leads to cell death.

ANVS401, also known as Posiphen, is an oral small molecule that prevents the production of these protein aggregates by interfering with their translation — the process through which a protein is made from a messenger RNA template by ribosomes, the cell’s protein-making machinery. In doing so, it is expected that ANVS401 will lower the levels of toxic proteins and improve transport within neurons (axonal transport). It was recently patented by Annovis.

Previous studies using cells in dishes and animal models of both Alzheimer’s and Parkinson’s have supported the treatment’s efficacy — for instance, ANVS401 was shown to lessen gut problems thought connected to alpha-synuclein buildup in mouse models of Parkinson’s.

The upcoming clinical trial plans to enroll a total of 68 people with Alzheimer’s or Parkinson’s at 15 sites across the U.S. Participants will be treated with ANVS401 for four weeks.

Trial researchers will evaluate the steps in the toxic cascade that lead to neuron death in both conditions, and assess how ANVS401 affects this cascade. In other words, the study will determine whether ANVS401 can lessen the accumulation of toxic proteins, and whether the reduction achieved leads to improvements in neuronal health and brain function.

This Phase 2 study will also assess the safety and tolerability of the investigational medication, as well as its effect on symptoms — including motor impairment and non-motor symptoms in Parkinson’s patients, and memory and cognitive problems in those with Alzheimer’s, the release stated.

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Parkinson’s Foundation Shares Early Results of PD GENEration Study

PD GENEration study

Preliminary results from the PD GENEration study demonstrate that comprehensive genetic testing and counseling, and the identification of rare genetic mutations linked to Parkinson’s disease, is feasible for the Parkinson’s community at large.

Launched in 2019 through the Parkinson’s Foundation and supported partly by Biogen, the study offers free genetic testing to Parkinson’s patients, as well as free genetic counseling to help them understand their results.

Although an estimated 15% of Parkinson’s cases might stem from genetic mutations, testing for clinically relevant genes remains uncommon.

Since launch, the PD GENEration study has tested at least 291 people, 52 of whom tested positive for a Parkinson’s-related mutation. This translates to a 17% detection rate, which is slightly higher than that estimated in the scientific literature.

According to a press release from the Parkinson’s Foundation, PD GENEration researchers expect the detection rate to rise as more people with Parkinson’s get tested.

“These interim findings represent the cornerstone in our success to lay the foundation for precision medicine in Parkinson’s disease,” said James Beck, chief scientific officer of the Parkinson’s Foundation, in the same press release. “By better understanding the genetic implications for people with [Parkinson’s], scientists will be able to move research and treatments forward towards a cure.”

The exact causes of Parkinson’s remain unknown. Although scientists believe that both genetic and environmental factors contribute to the condition, the extent to which each does so remains unclear. Expanding genetic testing may prove an effective way to shed light on that topic.

PD GENEration tests for seven genes with known Parkinson’s associations: GBA (glucocerebrosidase beta), LRRK2 (dardarin), PRKN (Parkin)PINK1 (PTEN induced putative kinase 1)PARK7 (DJ-1), VPS-35and SNCA (alpha-synuclein).

Testing for mutations in all of these genes is neither always available nor always covered by insurance. At-home kits are both limited in which changes they can detect and they cannot detect new mutations, which is a major goal of PD GENEration.

Some participants tested have shown extremely rare mutations, with some individuals even carrying multiple Parkinson’s-associated mutations. This information will contribute to a better understanding of the condition and should help in assessing the impact that certain mutations have on Parkinson’s progression and outcomes.

Although a genetic cause is unlikely to be found in most Parkinson’s patients, understanding the genetics of the condition better will improve the knowledge of its underlying biology, which will contribute to finding new therapeutic targets that could benefit many more people living with Parkinson’s.

“This study is critical for the entire [Parkinson’s] community,” said John L. Lehr, President and CEO of the Parkinson’s Foundation. “PD GENEration participants can now arm themselves with more information about their specific diagnosis while helping scientists advance [Parkinson’s] research. We will continue to expand the PD GENEration study to better serve the [Parkinson’s] community while moving research forward.”

The PD GENEration study is currently in a pilot phase. The Parkinson’s Foundation plans to expand testing sites to enroll up to 15,000 participants by late this year.

The pilot program experienced delays related to the COVID-19 pandemic, which caused a temporary suspension in testing. Although this means the program has fallen shy of its 600 anticipated participants so far, the foundation now is preparing a telemedicine-based approach, in which participants may use at-home genetic testing kits.

Virtual genetic counseling will be made available in English and Spanish. More information about where to find sites that are actively enrolling is available here.

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My Parkinson’s Treatment Conundrum

I was diagnosed with Parkinson’s disease in November 2015. Since then, I have explored both allopathic and naturopathic solutions.

From a naturopathic perspective, I immersed myself in Parkinson’s disease summer school, which dedicates a week to strategies to improve Parkinson’s outcomes. I also consult with a naturopathic doctor every few months. From a traditional medicine perspective, I consulted with 11 neurologists, seven of whom were movement disorder specialists.

To find the right treatment therapy for me, I have done the following:

  • Consulted with general neurologists, movement disorder specialists, and a naturopathic doctor
  • Educated myself with online courses and webinars
  • Conducted online research
  • Joined Facebook groups focused on Parkinson’s disease

I have finally concluded that no single treatment solution is for everyone. We all have unique and distinctive symptoms and different metabolism. I have traveled a rocky road over the past few years trying various medications and therapies for symptom relief.

My allopathy vs. naturopathy conundrum

As much as I am resistant to the idea of taking medications, I have learned to accept that I must take them to allow me to work out. My goal has always been to use exercise to ease my symptoms and slow disease progression.

The neurologists and the naturopathic doctor I consulted agree that exercise is one of the most important therapies for treating Parkinson’s.

Allopathic and naturopathic doctors sometimes have different opinions about using supplements and prescription drugs. My naturopathic doctor (ND) believes supplements can enhance the impact of prescription drugs. Also, she believes they might allow for the possibility of lower dosages of medications.

One of the movement disorder specialists (MDS) I visited did not approve of most of the supplements the ND recommended. He indicated there were no large-scale trials conducted that confirmed or denied how the supplements might interfere with the drugs or other body functions.

I respect the opinions of both the MDS and the ND and work closely with both of them to come up with a treatment plan we all can agree to.

The beauty is in the balance

I now realize that symptom relief is not achieved with an all or nothing scenario.

After much trial and error, I have come up with a combined naturopathic and allopathic approach that works for me. This solution allows me to accept and adjust to my “new normal” with no side effects and some symptom relief. This is the list that works for me and may not be appropriate for you. Always consult your doctors before making any changes to your health regimen.

My list includes:

  • Frequent exercise
  • Eating a plant-based diet
  • Massage
  • Physical and speech therapy
  • Carbidopa/levodopa
  • Neupro
  • Selegiline
  • Vitamins B12, C, and D3 (based on blood test deficiencies)
  • Fish oil
  • CoQ10
  • Glutathione
  • Infrared light therapy

My way of thinking may have hindered my progress to reach this point. After all the therapies I had done, I expected to feel like I did before I was diagnosed. Because I have a disease of the brain, that is unlikely to happen. Plus, as one ages (I am five years older now than I was when diagnosed), sometimes it is difficult to determine if a symptom (balance, slow movement, cognitive issues) is age-related or caused or accelerated by Parkinson’s disease.

Of course, this current regimen will need tweaking as time goes by. Dosages may have to be increased, not because the drugs lose their efficacy, but because Parkinson’s is a progressive disease.

My conclusion

As a person with Parkinson’s, the ball is in my court to find the right solution for me. Because we all have a different manifestation of the disease, everyone with Parkinson’s must find their unique treatment plan. It helps to arm ourselves with knowledge about our condition. We should not be afraid to challenge our treatment professionals. After all, we have the most experience in knowing how Parkinson’s affects our bodies.

“The conflict between preventive health and conventional medicine is not an either-or situation. For example, we will always need emergency rooms and people will always require health care services; yet it has become clear to me that the approach must be natural, it must be preventative, and must be individual.” – James L. D’Adamo


Note: Parkinson’s News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The opinions expressed in this column are not those of Parkinson’s News Today or its parent company, BioNews Services, and are intended to spark discussion about issues pertaining to Parkinson’s disease.

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DBS Eases Symptoms and May Slow Progression in Early Stage Patients, Study Says

DBS and early Parkinson's

When given to people at earlier stages of Parkinson’s disease, deep brain stimulation (DBS) reduces the complexity of their treatment, while safely providing long-term motor benefits and possibly slowing disease progression, data from a five-year pilot trial suggests.

A planned Phase 3 study has already received the go-ahead from the U.S. Food and Drug Administration (FDA). If these results are confirmed in a larger group of earlier stage patients, DBS will be the first therapy shown to be effective at slowing disease progression.

Findings were reported in the study, “Deep Brain Stimulation in Early-Stage Parkinson’s Disease: Five Year Outcomes,” published in the journal Neurology.

Deep brain stimulation is a surgical treatment for Parkinson’s disease that involves implanting a neurostimulator, a battery-operated device about the size of a pacemaker, in a person’s body to stimulate via electrical signals fine wires inserted into specific regions of the brain.

Shown to be safe and effective when used to stimulate the subthalamic nucleus (STN) — a brain region involved in movement control — in mid- to late-stage Parkinson’s patients, DBS studies in people at earlier stages are lacking. The safety and efficacy of STN DBS treatment, and its long-term effects, on this patient group are not known.

Researchers at Vanderbilt University Medical Center (VUMC) and colleagues conducted a single-site pilot trial (NCT0282152) to investigated the safety and tolerability of STN DBS in 30 people with early Parkinson’s (ages 50–75).

All, while off medication, were at stage two on the Hoehn & Yahr scale, signifying both sides of the body affected but stiffness and rigidity still at early stages. Their reliance on Parkinson’s medications ranged from six months to four years.

They were randomly assigned to either STN DBS in combination with optimal drug therapy, or to this drug regimen alone for two years.

Patients then entered an observational follow-up study (IRB040797), in which they were monitored for another three years.

Five-year data from 28 patients who completed both study parts found that those given STN DBS alongside optimal drug therapy required lower doses of levodopa to control symptoms, compared with those on an optimal drug regimen alone (a daily average of 774 mg versus 1,158 mg).

In addition to requiring lower levodopa doses, patients given STN DBS were also 16 times less likely to need multiple medications (polypharmacy) for symptom control at five years, compared with those given optimal drug therapy alone.

Through these five years, those on continuous drug therapy were seen to have an almost five times higher risk of worsening rest tremor, and a two times higher chance of a worsening of their motor symptoms in general, analyses showed.

The incidence of adverse events and the overall safety profile was similar in both treatment groups.

“These results suggest that early STN DBS + ODT is a safe Parkinson’s disease treatment with the potential to provide long-term, sustained motor benefit over standard medical therapy while reducing the need for, and complexity of, anti-parkinsonian medications and their associated complications,” the researchers wrote.

A randomized, double-blind, Phase 3 trial (IDEG050016), led by VUMC, plans to recruit about 130 patients from 20 U.S. centers, to investigate the potential of DBS in slowing disease progression when early in the course of the disease.

“With this pilot study, we’ve shown that if DBS is implanted early it’s likely to decrease the risk of progression, and if this is borne out in our larger study it would be a landmark achievement in the field of Parkinson’s disease,” David Charles, MD, a professor and vice chair of neurology at VUMC, and the study’s senior author of the study, said in a press release.

Given the one trial’s preliminary nature, however, Charles stressed its findings should not lead to any changes in clinical treatment of Parkinson’s.

The Neurology study received partial support from Medtronic, which manufactures the DBS system. Its authors, all with VUMC, also report that they had full editorial independence.

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