All Science News articles summarize a research study and are not an official opinion, endorsement or position of the Parkinson’s Foundation’s.

Two parts within our brain require healthy dopamine regulation and transmission to do their jobs:

• The basal ganglia: messengers that sort out information for the spinal cord and cerebellum and are associated with various functions, including motor control, motor learning, executive functions and behaviors, and emotions.
• The cerebellum: involved in movement and coordination, walking, posture, reflexes, and eye and head movement; it also sends instructions to our muscles that adjusts our posture and keeps our bodies moving smoothly.

Adults with attention-deficit hyperactivity disorder (ADHD) have been shown to have damaged dopamine neurons in the basil ganglia, and, commonly have cerebellar abnormalities, much like people with Parkinson’s disease (PD). So, are ADHD and PD somehow connected? Perhaps.

A recently published study in the journal, Neuropsychopharmacology, sought to determine if having ADHD and/or its treatment, increases the risk of having basal ganglia and cerebellar diseases. In this 20-year follow-up retrospective cohort study, a total of 190,586 patient records (31,796 with ADHD and 158,790 without ADHD) from Utah were examined. People with no prior PD diagnosis or symptoms, no basal ganglia/cerebellar disease and those with a history of substance abuse were excluded from participating in the study.

Results

• Overall, ADHD was associated with a 2.4-fold increased risk of basal ganglia and cerebellar (BG&C) diseases.
• Of the people diagnosed with a basal ganglia or cerebellar disease, 96 of non-ADHD (32.3%) and 56 of people with ADHD (33.7%) were diagnosed specifically with Parkinson’s.
• Though the numbers of people with PD in this study was small, a 2.6-fold increased risk of Parkinson’s was observed for people with ADHD compared with non-ADHD (consistent with risk overall of BG&C diseases).
• In people with ADHD who were prescribed stimulant medications, the risk of PD was 4-fold that of people who do not have ADHD.
• Lastly, the risk of young-onset BG&C diseases before age 50 years was increased in people with an ADHD history, particularly in those that were prescribed stimulants.

In terms of comparing people with ADHD to non-ADHD, (for all basal ganglia/cerebellar diseases, not just PD):

• People with ADHD prescribed stimulants were significantly more likely to have BG&C diseases compared to those without ADHD.
• People with ADHD prescribed stimulants were at greater risk of having BG&C diseases compared to than people with ADHD who were not prescribed stimulants.

What Does This Mean?

People with an ADHD diagnosis were shown to have more than 2-fold increased risk of a subsequent diagnosis of BG&C diseases — including and specifically PD — compared to people with no history of ADHD. That 2-fold increased risk includes BG&C diseases such as secondary parkinsonism, other degenerative diseases of the basal ganglia, and essential tremor.

Of particular note, for people on ADHD medication, their risk of PD doubled to 4-fold, compared to people without ADHD. Further, according to the most recent data available from the Centers for Disease Control and Prevention (CDC, 2018), approximately 9.4% of children 2-17 years of age (6.1 million) had ever been diagnosed with ADHD, and almost two thirds (62.0%) were taking medication (Danielson et al., 2018). While results from this study suggest people taking certain ADHD medications may be at an increased risk for earlier-onset BG&C diseases (including PD), this is just a single study, and results have not been replicated. In addition, even with an increase in risk, the overall risk in developing PD is still very small. Always talk to your doctor regarding any health concerns you may have.

Learn More

The Parkinson’s Foundation believes in empowering the Parkinson’s community through education. Learn more about the connection between ADHD and Parkinson’s in the below Parkinson’s Foundation resources or by calling our free Helpline at 1-800-4PD-INFO (473-4636).

• Episode 21: What Other Conditions Are Related to Parkinson's
• Conditions Related to Parkinson's
• ​Dopamine Agonists

All Science News articles summarize a research study and are not an official opinion, endorsement or position of the Parkinson’s Foundation’s.

For years, drinking coffee has been associated with having a reduced risk of developing Parkinson's disease (PD). In fact, a 1968 study suggested that coffee drinkers were less like to get PD (Nefzger, Quadfasel, & Karl, 1968). Since then, multiple epidemiologic studies have confirmed the PD/coffee connection (Ascherio et al., 2003; Ascherio et al., 2004; Fujimaki et al., 2018). Researchers have mostly attributed the protective effect to the caffeine component (Lee et al., 2013).

However, coffee is more than a caffeine delivery system. Coffee has more than 1,000 different compounds, including organic acids, sugars, amino acids and fatty acids. One such fatty acid called Eicosanoyl-5-hydroxytryptamide (EHT) has been getting quite a bit of buzz in the PD research community; and, for good reason. A recently published study titled, “Synergistic neuroprotection by coffee components eicosanoyl-5-hydroxytryptamide and caffeine in models of Parkinson’s disease and DLB” (Yan et al., 2018), provides some compelling insights into the possible biochemical protective mechanisms of our cup of joe.

A recently published study in the journal, Neuropsychopharmacology, sought to determine if having ADHD and/or its treatment, increases the risk of having basal ganglia and cerebellar diseases. In this 20-year follow-up retrospective cohort study, a total of 190,586 patient records (31,796 with ADHD and 158,790 without ADHD) from Utah were examined. People with no prior PD diagnosis or symptoms, no basal ganglia/cerebellar disease and those with a history of substance abuse were excluded from participating in the study.

Here’s what the researchers did: over a six-month period, they treated groups of two different PD model mice with various combinations of caffeine and EHT (caffeine alone, EHT alone, or caffeine and EHT together) to study their effects on both brain and behavior. There was also a group of mice that received no treatment. Then they performed several behavioral tests to study their movement, as well as study their brains for signs of alpha-synuclein clumps (which result in Lewy bodies, the pathological hallmark of PD), neurodegeneration and inflammation. The study found that the untreated mice had significant amounts of clumped α-synuclein in their brains, increased inflammation and loss of neurons, as well as significant deficits on three different behavioral tests. In general, the mice treated with EHT or caffeine alone showed either no or minimal improvement in any of these measures. However, the mice treated with the combination of EHT and caffeine together showed significant improvements in all of these measures.

Results

• More specifically, mice treated with both EHT and caffeine together:
• Had less alpha-synuclein clumping in the brain
• Maintained better neuron integrity and function
• Had less brain inflammation
• Displayed less movement symptoms

What Does This Mean?

In this study, a synergistic combination of EHT and caffeine was shown to slow down the progression of the neurodegeneration associated with PD in mice — which has potentially readily available therapeutic implications. In addition, previous research has demonstrated that caffeine enhances dopamine signaling in the brain (Volkow et al., 2015); and, it’s the death of dopamine-producing cells that results in movement symptoms of PD (and why dopamine replacement medication is the gold standard treating PD symptoms).

For years, coffee consumption has been suggested to play a protective role in developing PD. However, it was never clear what exactly in coffee had this effect. This study suggests that two compounds, caffeine and the fatty acid EHT, work together to protect against alpha- synuclein clumps and dopamine neuron loss in two different PD models of mice. Interestingly, these effects were seen even using very low doses of the compounds. If the results of this study can be replicated by other researchers, then identifying that delicate balance of safety and effectiveness for humans is likely an essential step that researchers will be investigating in the future.

Learn More

The Parkinson’s Foundation believes in empowering the Parkinson’s community through education. Learn more about the connection between dopamine, caffeine, Lewy bodies and alpha-synuclein and Parkinson’s in the below Parkinson’s Foundation resources or by calling our free Helpline at 1-800-4PD-INFO (473-4636).

• The Latest in Nutrition and Parkinson’s Disease

Marijuana and Parkinson’s disease (PD) is a hot topic. Watch our newest video, Neuro Talks, where James Beck, PhD, Parkinson’s Foundation Chief Scientific Officer, explains what the PD community should know about marijuana.

What are the risks of marijuana for a person with PD? Can it help with symptoms? What is the Parkinson’s Foundation doing to learn more? Find out in this four-minute video:

For more information, call the Parkinson’s Foundation Helpline today at 1-800-4PD-INFO (473-4636) or email us at Helpline@Parkinson.org with your Parkinson’s questions in English or Spanish.

All Science News articles summarize a research study and are not an official opinion, endorsement or position of the Parkinson’s Foundation’s.

People with Parkinson’s disease (PD) commonly suffer from tremors and other movement symptoms, such as slowness and stiffness, caused by the loss of dopamine-producing nerve cells in an area of the brain called the substantia nigra. The cornerstone therapy for reducing these symptoms is the drug, levodopa. Often referred to as simply L-dopa, this drug works by helping to replenish the brain’s supply of dopamine. However, with long-term use of L-dopa, upwards of half of people with PD can develop levodopa-induced dyskinesia (LID) — a side effect that causes involuntary rapid jerking and twisting, or slow and extended muscle spasms. The severity of these side effects can range from bothersome to incapacitating.

A recently published study, titled, “Safety and tolerability of IRL790 in Parkinson’s disease with levodopa-induced dyskinesia—a phase 1b trial” (Svenningsson et al., 2018), investigated an experimental small molecule compound called, IRL790, which blocks a dopamine receptor called D3. Why D3? Studies in both animals and people with PD have found that long-term treatment with levodopa results in higher levels of D3 in the brain, which is believed to be what’s causing the LID side effects. Conducted at three university hospital outpatient clinics in Sweden, this was a randomized, double‐blind, placebo‐controlled study.

Ranging in age from 50 to 85, a total of 15 study participants with PD (9 men, 6 women) swallowed one oral capsule twice a day for four weeks of either IRL790 (11 people) or a placebo (4 people). All PD medications, including levodopa, were unchanged for at least 30 days and throughout the study period. Five clinic visits were required, with a follow-up phone call on day 21. A final follow-up visit was conducted within 10 days after the last dose. The starting dose prescribed for all participants was 10 mg (twice a day), with individual dose adjustments allowed up to a maximum of 40 mg twice a day, as needed. Doses were adjusted up to day 14 of the study, after which the dose remained stable.

The primary objective of this study was to investigate the safety and tolerability of the new drug, IRL790, including measuring frequency, seriousness and intensity of adverse events, physical examination, electrocardiogram (ECG) recordings, vital signs and safety laboratory measurements. To record movement data, i.e., dyskinesia and bradykinesia (slowness of movement), participants wore a kinetigraph device attached to their right or left wrist (their parkinsonian dominant side) for seven days priors to the study to establish a baseline, and then wore the device again for the last seven days of the trial.

Results

• A total of 13 participants completed the study. Two of the participants were withdrawn from the study due to possible adverse events associated with drug (one due to difficulty breathing and dizziness, and the other due to edema and redness of the feet).
• A total of 62 adverse events was reported by 14 participants (93.3%) — none were reported as serious and most could be mitigated by dose adjustments. All participants treated with a placebo experienced at least one adverse event.
• The average stable IRL790 dose was 18 mg daily.
• Among participants treated with IRL790, 55.5% were assessed as having an improved global clinical condition.
• Participants were reported to be in a steady state for plasma drug concentration after taking IRL790 for 14 days.
• Participants receiving IRL790 experienced a reduction in dyskinesia, without a reduction in the positive effects of levodopa.

What Does This Mean?

In 1961, L-dopa was hailed for its "miraculous" effect in people with PD (Hornykiewicz, 2010). However, by 1971 there were already studies investigating whether levodopa  was causing dyskinesias (Mones, Elizan, & Siegel, 1971). Today, we know that dyskinesia is a side effect associated with long-term use of L-dopa. Long term treatment with L-dopa results in making too much of the dopamine receptor called D3. While one may think that having a lot of a dopamine receptors sounds like a good thing for PD, in this case, it’s not. D3 is believed to produce the unwanted side effect of LID. The Svenningsson et al (2018) study supports this by demonstrating that by specifically blocking the D3 with the novel drug, IRL790, the negative LID symptoms could be significantly reduced without compromising the positive effects of L-dopa.

More than half of the study participants experienced less dyskinesia — and with no serious side effects. That’s not just encouraging, that’s groundbreaking. IRL790 may have the potential to become a game-changer in the treatment of PD. Of course, more research still needs to be done, as this was a phase 1 trial conducted in a small group of people. Researchers are already actively recruiting study participants for a Phase 2 clinical trial to help establish optimal dosing and are hoping to recruit 74 people with PD to participate (ClinicalTrials.gov, 2018). 

Learn More

The Parkinson’s Foundation believes in empowering the Parkinson’s community through education. Learn more about dyskinesia and PD medication by vising the below Parkinson’s Foundation resources or by calling our free Helpline at 1-800-4PD-INFO (473-4636) for answers to all your Parkinson’s questions.

• Expert Briefings: PD Medications: What’s New?
• Dyskinesia
• Bradyknesia (Slowness of Movement) 

Over the next three years the Parkinson’s Foundation will invest more than $50 million to Parkinson’s disease (PD) research and clinical care. At the heart of our research initiatives are scientists and researchers who have received Foundation awards to improve our understanding of Parkinson’s, which will ultimately lead us to a cure.

Gulcin Pekkurnaz, PhD, is a Stanley Fahn Junior Faculty Awardee who is working to understand how aging affects dopamine in Parkinson’s.

Parkinson’s disease develops when the cell’s energy factories, called mitochondria, start to fail in dopamine neurons or nerve cells. Dopamine is a brain chemical messenger that carries information between neurons and helps us to move smoothly. People with Parkinson’s have low levels of dopamine in the brain due to dopamine neurons dying.   

People with Parkinson’s do not develop disease symptoms until later in life. This indicates aging-associated changes are involved in the development of the disease. With aging, both mitochondrial function and cellular metabolism decline. We hope to gain a better understanding of why this happens.

Dr. Pekkurnaz at University of California San Diego received a research grant to study the mitochondria from dopamine nerve fibers in animals. Her goal is to identify what happens to dopamine neuron mitochondria before Parkinson’s symptoms start. To accomplish this, she will develop new technology that will allow us to analyze unique mitochondrial features from dopamine neurons as a function of age.

We hope to gain fundamental insights into how the dopamine neuron energy supply works and they start to fail. These findings can lead to potential drug targets for Parkinson’s.

The Parkinson’s Foundation Stanley Fahn Junior Faculty Award helps ensure promising early career scientists stay in the PD research field. This award provides junior investigators the support they need to develop their own independent funding source.

What’s Next: Reporting Our Findings

Parkinson’s Foundation research awards fund Parkinson’s studies than can span up to three years. Scientists submit yearly progress reports to the Parkinson’s Foundation, and we report findings once the studies have concluded. Stay up to date with our latest research findings at Parkinson.org/Blog.

Since its launch in the late 1960s, carbidopa/levodopa (brand name SINEMET®) is still the most effective Parkinson’s disease (PD) motor symptom treatment. However, it doesn’t address all facets of the disease. Medications to bolster its effectiveness and treat PD-related non-motor symptoms are newly available or just on the horizon.

This article is based on a Parkinson’s Foundation Expert Briefings webinar exploring innovative PD treatments by Rajesh Pahwa, MD, Director, Parkinson and Movement Disorder Division, University of Kansas Medical Center, a Parkinson’s Foundation Center of Excellence.

Pioneering Medicine

It’s an exciting time for PD drug advances. While gene therapy benefits are still being studied, many new medications are on the market or are soon to be. These new treatments are designed to tackle Parkinson’s disease challenges, including:

• Psychosis – hallucinations and delusions.
• Orthostatic hypotension – a blood pressure drop when rising or standing.
• “Off” time – when symptoms and movement difficulties increase.
• Dyskinesia – abnormal, involuntary muscle movement.
• Dementia – memory and thinking declines.
• Falls – PD can cause slowness of movements, increasing falling and other risks.

Current Treatments

Parkinson's Disease Psychosis

PD-associated psychosis can be caused by the disease itself or PD medications. Challenging for people with PD and caregivers, symptoms include confusion, delusions and hallucinations. Report any changes to your medical team.

Pimavanserin (Nuplazid®), newer to the market, is the only approved treatment for PD psychosis. It does not block dopamine or worsen motor symptoms. It can improve hallucinations, delusions, night-time sleep and daytime sleepiness. Side effects include nausea, confusion and hallucinations.

Orthosstatic Hypotension

From 20 to 50 percent of people living with PD experience a significant blood pressure drop upon standing, known as orthostatic hypotension; certain medications can worsen this. This drop can cause lightheadedness or fainting, and other symptoms.

Droxidopa (NORTHERA®) treats lightheadedness. It should not be taken within five hours of bedtime. Side effects include headache, dizziness, nausea, fatigue and high blood pressure when lying down.

"Off"-Time Advancements

Levodopa is synthesized in the brain into dopamine, making it key to PD symptom management. But several factors can interfere with steady, accurate dose delivery. When medication is not taken on time, or absorption is delayed, freezing and other sudden and debilitating motor symptoms can occur. These newer medications can help tackle “off” periods.

Carbidopa/Levodopa Enteral Suspension (Duopa™)

Duopa™ therapy, a newer carbidopa/levodopa treatment, can benefit people with advanced PD who respond well to levodopa and experience three or more “off” hours daily. It’s delivered in gel form (called enteral suspension). Duopa™ users must first have surgery to place a tube in their intestine that is later connected to a pump that delivers Duopa™.

Safinamide (XADAGO®)

Safinamide tablets (XADAGO®) are an add-on treatment for people with Parkinson’s taking carbidopa/levodopa and experiencing “off” times. Safinamide is a monoamine oxidase B (MAO-B) inhibitor that can reduce “off” times up to 55 minutes a day, without dyskinesia. Interactions include other MAO-B class drugs, certain antidepressants and the cold medicine dextromethorphan. Anyone taking a PD medication should talk to their doctor and pharmacist about potential drug interactions.

On-Demand Therapy

Levodopa Inhalation (INBRIJA™)

The levodopa inhalation powder INBRIJA™ is an add-on drug for “off” periods in people taking carbidopa/levodopa. Administered via inhaler, it can be used up to five times a day, improving “off” symptoms as soon as 10 minutes and lasting up to 60 minutes. This can improve symptoms for people with decreased gut motility while waiting for oral carbidopa/levodopa to take effect.

Amantadine ER capsules (GOCOVRI®)

This is the only medication to treat dyskinesia and “off” time in people with PD taking carbidopa/levodopa. It must be taken before bedtime and provides control of dyskinesia upon awakening and throughout the day. It can cause hallucinations and lightheadedness. This medication is different from immediate-release amantadine and amantadine ER tablets (OSMOLEX ER™) which are not approved for dyskinesia or “off” time.

IncobotulinumtoxinA (XEOMIN)

More than 50 percent of people with PD can have excessive drooling, causing skin breakdown around the mouth, odors, embarrassment or choking. Two injections on the face, every 3-4 months of XEOMIN, can manage symptoms.

Future Therapies

Sublingual Apomorphine

Apomorphine is administered through injections under the skin. Sublingual apomorphine, dissolved under the tongue, can relieve “wearing off” episodes for people with Parkinson’s disease in 15 minutes and lasts up to 90 minutes. Side effects can include nausea, sleepiness, and dizziness.

Rimabotulinumtoxin B (MYOBLOC®)

Rimabotulinumtoxin B is currently approved for dystonia and used off-label for drooling. It is undergoing trials to treat drooling. Side effects include dry mouth, mild swallowing difficulty, mild chewing weakness and saliva thickness changes.

Adenosine A2 Antagonist: Istradefylline

A group of brain circuits called the basal ganglia play a role in causing PD symptoms. The basal ganglia have adenosine A2A receptors that are located next to dopamine receptors. Scientists believe that activating the dopamine receptor or blocking the adenosine A2 receptor can improve PD symptoms.

Istradefylline, an adenosine A2A receptor antagonist shows mild motor symptom fluctuation improvements. Approved for use in Japan, Istradefylline has also received U.S. FDA approval.

Subcutaneous Apomorphine Infusion

Available in Europe, subcutaneous apomorphine treatment offers a less invasive motor fluctuation treatment option. A small delivery tube placed under the skin is connected to an apomorphine-filled pumping device. It can reduce daily “off” time and possibly dyskinesia by reducing needed levodopa dose. Those with hallucinations and dementia might not be candidates.

Subcutaneous Carbidopa/Levodopa Pump

Two companies are currently developing pumps for continuous under-skin carbidopa/levodopa therapy to reduce “off” times and motor symptom fluctuations. The pumps can be used around the clock and don’t require surgery.

Carbidopa/levodopa extended release

New tests are underway for extended-release carbidopa/levodopa therapy to reduce “off” times and motor symptom fluctuations.

• Accordion Pill™, Carbidopa/Levodopa (AP-CD/LD) maker, will begin its Phase 3 clinical trial of new delivery technology. The Accordion Pill slowly releases treatment in the stomach for more steady absorption.
• IPX203, an investigational extended-release oral carbidopa/levodopa formulation that increases “on” time, is currently enrolling participants in its Phase 3 clinical study.

Opicapone

Experimental opicapone is a COMT (catechol-o-methyl transferase) inhibitor. This drug class can extend levodopa benefits. Available in Europe, opicapone reduces “off” time for people with PD experiencing levodopa effectiveness fluctuations.

If you have any questions about managing Parkinson’s, PD medications or caregiving, call our Helpline at 1-800-4PD-INFO (473-4636) on weekdays from 9 a.m. to 8 p.m. You can also check out these resources:

• Prescription Medications
• For Caregivers
• Episode 6: New Levodopa Delivery Methods for Parkinson’s
• Parkinson’s Treatment

Many people with advanced Parkinson’s disease (PD) suffer from gait (walking) dysfunction, freezing of gait and postural instability. These symptoms can cause falling, resulting in a multitude of injuries, a loss of personal freedom, caregiver stress and a reduction in the quality of life (Pirker & Katzenschlager, 2017; Samotus, Parrent, & Jog, 2018). Medications, such as levodopa, rarely helps with these specific motor symptoms, while deep brain stimulation (DBS) results are limited and unpredictable for these particular symptoms. The fact is, current PD medications, therapies or surgical procedures do not effectively address this debilitating unmet need. This lack of options might be changing, due to an intervention called spinal cord stimulation (SCS).

Surgically implanted, SCS is a device that alters nerve activity by sending a low-voltage electrical current to select areas of the spinal cord. These voltage settings are adjustable post-implantation, which allows for personalized optimization. SCS is currently used to treat people with chronic back and nerve pain, as well as for neuropathic pain, such as diabetic neuropathy, and chemotherapy or radiation induced neuropathy. Exploring its usefulness for people with PD has just begun.

Recently published in the journal of Movement Disorders, a study titled, “Spinal Cord Stimulation Therapy for Gait Dysfunction in Advanced Parkinson's Disease Patients” (Samotus et al., 2018), a six-month pilot study recruited five PD participants with advanced PD. These participants were chosen based on convenience. Participants were an average age of 71 with average disease duration of 14 years. Participants who had a stroke (or any other neurological diseases) and moderately severe parkinsonism in the context of unstable medication treatment (Samotus et al., 2018) were not included in the study. All five participants underwent mid-thoracic spinal cord stimulation surgery and a dorsal spinal cord stimulator was implanted in the epidural space (near the lower back).

This study evaluated SCS efficacy by clinical evaluation and objective gait analysis before and after surgery. A 20-foot gait detection mat equipped with pressure sensors — a relatively new technology (Muro-de-la-Herran, Garcia-Zapirain, & Mendez-Zorrilla, 2014) — was used to measure various features of gait such as step length, stride width, stride velocity, step time, stance, swing, and percentage of time one or two feet are on the ground. To measure freezing of gait, a timed sit-to-stand test was used, as well as an automated freezing detection program that measured changes in foot pressure.

The study also evaluated different frequency and pulse width combinations via gait analysis multiple times 1-4 months after surgery. Eleven frequency and pulse width SCS combinations were tested. Of note, the freezing questionnaire, the Unified Parkinson’s Disease Rating Scale (UPDRS) motor items, Activities-specific Balance Confidence Scale (ABC), and Parkinson’s Disease Questionnaire (PDQ-8) were given to all five participants at every visit.

Results

• Six months post-implantation, there was an average improvement of 33.5%, in the UPDRS motor score, 26.8% in the FOG questionnaire and 71.4%, in the ABC score.
• Significant improvement in all participants’ confidence to complete daily activities, especially around and outside the house, occurred in week six and improvements were maintained following week 10, resulting in an average improvement of 71.4% in week 24 compared to before the SCS implantation.
• The number of freezing episodes captured on the gait mat dropped quickly from an average of 16 before surgery to zero six months after surgery, per study participant, on levodopa and off stimulation.
• Stride velocity significantly improved by 42.3%, mean step length improved by 38.8% and the time in seconds for a participant to arise from a chair to a standing position improved by 50.3%.
• By week 24, two of the five participants were able to walk without assistance whereas they needed it before surgery, and three of the five participants reported that their activities of daily living were now only moderately affected by gait dysfunction, whereas they were severely affected before surgery.
• One participant reported no longer needing to use his wheelchair and was solely using a walker by the end of the study,
• No adverse effects were reported.

What Does This Mean?

First presented at the 21st International Congress of Parkinson’s Disease and Movement Disorders, this is the first study to use objective gait technology to assess SCS efficacy for people with advanced PD.

Ranging from significant improvement in all study participants’ confidence in performing activities of daily living, to one of the participants no longer needing a wheelchair, to sustained improvements in gait, the pilot study results are encouraging. Stride velocity improved by 42.3%, average step length improved by 38.8% and the time in seconds for a participant to stand up from a chair improved by 50.3%. Perhaps most impressive was the reporting of zero freezing episodes six months after SCS surgical implantation with no adverse effects.

Further, SCS technology proved to be personalized, as doctors were able to adjust technology after implantation in order to provide the optimal therapeutic value. Unlike most surgical procedures, SCS is reversible. Also, important to note, SCS runs on batteries — some are rechargeable, and others last up to 5 years (NIH, 2019).

Although it is a small pilot study, it nonetheless demonstrated that SCS may offer some significant therapeutic value for people with advanced PD. A larger and longer clinical study is warranted to see if these rather remarkable preliminary results can be replicated.

Learn More

The Parkinson’s Foundation believes in empowering the Parkinson’s community through education. Learn more about freezing, balance, gait and falls and Parkinson’s in the below Parkinson’s Foundation resources or by calling our free Helpline at 1-800-4PD-INFO (473-4636).
• Walking with Parkinson’s: Freezing, Balance and Falls
• Expert Briefings: Gait, Balance and Falls in Parkinson's Disease
• Podcast Episode 18: Stall the Fall

Over the next three years the Parkinson’s Foundation will invest more than $50 million to Parkinson’s disease (PD) research and clinical care. At the heart of our research initiatives are scientists and researchers who have received Foundation awards to improve our understanding of Parkinson’s, which will ultimately lead us to a cure.

Much of our understanding of Parkinson’s disease comes from genetic studies. The most common genetic changes linked to Parkinson’s occur in the GBA gene. The role of GBA in cells is to break down complex lipids in the cell’s “recycling bin,” the lysosome.

Roy N. Alcalay, MD, MS,  is a Stanley Fahn Junior Faculty Awardee at Columbia University Medical Center who received a Parkinson’s Foundation grant to identify the parts of lipid metabolism that are most affected by Parkinson’s and to find potential drug targets to correct them. With cutting-edge technology, Dr. Alcalay’s research will measure 520 lipids in blood samples from people with Parkinson’s and from people without the disease. In people who carry Parkinson’s-related mutations in the GBA or alpha-synuclein genes, we will test if altered lipid levels are linked to Parkinson’s diagnosis.

Dr. Alcalay’s research will also analyze 600 people with Parkinson’s and 400 without the disease, testing for genetic changes in 32 genes involved with lipid metabolism. His team will look at the relationship between lipid levels and the activities of lysosome enzymes, also assessing genetic changes in the enzymes’ genes. Our hope is that Dr. Alcalay’s and his team can identify novel drug targets and biomarkers for Parkinson’s that will improve diagnosis and treatment of the disease.

The Parkinson's Foundation Stanley Fahn Junior Faculty Award helps ensure promising early career scientists stay in the PD research field. This award provides junior investigators the support they need to develop their own independent funding source.

What's Next: Reporting Our Findings

Parkinson’s Foundation research awards fund Parkinson’s studies than can span up to three years. Scientists submit yearly progress reports to the Parkinson’s Foundation, and we report findings once the studies have concluded. Stay up to date with our latest research findings at Parkinson.org/Blog.

Over the next three years the Parkinson’s Foundation will invest more than $50 million to Parkinson’s disease (PD) research and clinical care. At the heart of our research initiatives are scientists and researchers who have received Foundation awards to improve our understanding of Parkinson’s, which will ultimately lead us to a cure.

Alpha-synuclein (αSyn)is a protein central to Parkinson’s. In Parkinson’s, this protein misfolds, forming a clump in the brain. Large clumps are known as “Lewy bodies” and disrupt the brain’s normal functioning in people with PD.

Alpha-synuclein is also involved in the regulation of lipids and fatty acids, which help to prevent disease-associated changes in the brain. In Parkinson’s, alpha-synuclein is destabilized. This makes the protein more likely to break down and clump together. What triggers the destabilization of alpha-synuclein in the human brain remains one of the most critical questions in the study of Parkinson’s.

Tim Bartels, MSc, PhD, from Brigham and Women's Hospital Inc., received a Parkinson’s Foundation research grant to gain a better understating of alpha-synuclein in Parkinson’s. He and his research team will analyze the interactions of lipids with different forms of alpha-synuclein in human brain samples. Dr. Bartels hopes to discover which lipids and fatty acids prevent alpha-synuclein aggregation and which ones promote aggregation.

He will also investigate the normal interaction of alpha-synuclein with fatty acids and lipids. Together, these approaches should suggest how to develop drugs that stabilize alpha-synuclein by mimicking the beneficial lipids and fatty acids.

Dr. Bartels team may also find a signature of specific lipids and fatty acids that are associated with PD. This could be an easily accessible biomarker — a biological molecule that is a sign of disease — for Parkinson’s. Having a biomarker for Parkinson’s could lead to earlier diagnosis of the disease. This can improve outcomes for people living with PD.

The Parkinson’s Foundation Stanley Fahn Junior Faculty Award helps ensure promising early career scientists stay in the PD research field. This award provides junior investigators the support they need to develop their own independent funding source.

What’s Next: Reporting Our Findings
Parkinson’s Foundation research awards fund Parkinson’s studies than can span up to three years. Scientists submit yearly progress reports to the Parkinson’s Foundation, and we report findings once the studies have concluded. Stay up to date with our latest research findings at Parkinson.org/Blog.

First described as a common symptom of Parkinson’s disease (PD) more than 20 years ago, PD-related fatigue remains an under-recognized, clinically significant, disabling symptom that can diminish quality of life (Herlofson et al., 2018; Kluger et al., 2016). Often occurring prior to movement symptoms of PD — tremor, rigidity and bradykinesia — (Chong, Albor, Wakade, & Morgan, 2018), PD-related fatigue doesn’t go away over time and getting more rest does not help (APDA, 2017).

The 2014 Parkinson’s Foundation Conference on Fatigue found that half of all people with PD reported fatigue as a major problem, and one-third shared that fatigue is their single most disabling symptom. The conference brought together a multidisciplinary group of experts, including a scientist studying fatigue in breast cancer. Research in breast cancer has shown that inflammation plays a large role in fatigue, even years after treatment when patients are in remission. One of the questions that came out of the 2014 conference was whether inflammation also plays a role in fatigue in PD.

Recently published in the journal, Acta Neurologica Scandinavica, a study titled, “Inflammation and fatigue in early, untreated Parkinson’s” (Herlofson et al., 2018) sought to explore the possible association of proinflammatory cytokines (a type of substance released by a cell that promotes inflammation) and fatigue in PD. Considered the boss of the immune system, cytokines are chemical messengers responsible for up-regulating (initiating), as well as down-regulating (turning off) the immune response. Studies have found that proinflammatory cytokines may play a role in PD and have been proposed to be part of an immune response to tissue damage (Williams-Gray et al., 2016)

Funded by the Parkinson’s Foundation, Karen Herlofson, MD, led a study measuring 13 different inflammatory markers and adhesion molecules (helps cells stick to one another), obtained with a simple blood-draw in people with PD who had also been assessed for fatigue levels.

The study recruited 212 participants who were newly diagnosed with PD and untreated. They were initially recruited from the Norwegian ParkWest Project — a population-based prospective longitudinal cohort study of newly diagnosed, untreated people with PD. However, after excluding those with decreased cognitive function, symptoms of depression, excessive daytime sleepiness, apathy, other diseases or relevant medications, a total of 47 participated in this study; 24 had low fatigue scores and 23 had high fatigue scores.

Demographic data (age, years of education, weight, and height) were collected during a semi-structured interview. Disease severity was assessed by the Unified Parkinson’s Disease rating Scale part III (UPDRS III). Fatigue was assessed by the Fatigue Severity Scale (FSS), a self-administered questionnaire, which focuses upon the physical social, and mental aspects of fatigue. All 47 participants had their blood drawn the same day as the clinical assessment and all fasted the night before. The blood draw occurred between 8 and 10 a.m., to minimize confounding factors caused by circadian rhythm.

Results

Compared to the study participants without fatigue, participants with fatigue:

• Had significantly higher levels of the cytokine IL1-Ra and the adhesion molecule VCAM-1
• Had more advanced disease, as measured by the Unified Parkinson’s Disease Rating Scale (UPDRS) motor score.
• Had lower cognitive function, as measured by the MMSE (Mini-Mental State Examination).
• Had more depression, as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS).
• Had less excessive daytime sleepiness, as measured by the Epworth Sleepiness Scale (ESS), showed no correlations between IL1-Ra or VCAM-1 with age, sex, years of education, BMI, UPDRS, MADRS, MMSE, apathy, or ESS.

What Does This Mean?

PD-associated fatigue can have a detrimental impact on quality of life; yet, the underlying biological cause remains unknown. This study found that having higher blood levels of the inflammatory markers IL1-Ra and VCAM-1 were associated with higher fatigue levels in newly diagnosed, untreated participants with PD. If true, and an altered immune response is indeed a factor, this finding may offer new targets to explore for future treatment — as the immune system is a promising therapeutic target for disease modification.

Additionally, these findings may, if correct, offer some future early PD diagnostic potential — as fatigue commonly presents before the classic hallmark symptoms of PD. We know that inflammation contributes to neurodegeneration in the brain. Whether or not cytokines are increased as a result of the stress and tissue damage that are a consequence of PD — or whether the inflammation happens prior to the fatigue — is a question that must be answered. This study brings us one step closer

Learn More

The Parkinson’s Foundation believes in empowering the Parkinson’s community through education. Learn more about the connection between fatigue and Parkinson’s in the below Parkinson’s Foundation resources or by calling our free Helpline at 1-800-4PD-INFO (473-4636).

• Fatigue
• Fatigue & Parkinson's