Impulsivity and Parkinson’s: The Itch that Must Be Scratched

 NOVEMBER 9, 2018  DR. C'S JOURNEY WITH PD 

Impulsivity is a symptom commonly associated with both Parkinson’s disease (PD) and some of the medications used to treat it.

Impulsivity involves acting on urges with little thought to the consequences — that seven-year itch that feels like it must be scratched — regardless of the problems that may arise. Impulsivity takes many forms. My previous columns about terror (exaggerated emotion) and irritability (the grouch) both speak to issues centered around impulsivity.

The cognitive pathways that involve impulsivity are simplified in the graphic below with the important checkpoints labeled as CP.1, CP.2, and CP.3. These checkpoints are where the impulse signals (sensory data) are heightened. The more heightened they become, the more difficult it is to alter their eventual destination of impulsive action.

PD creates problems at these three checkpoints and thus creates the false perception of heightened signal input and the false impression that it is the itch that must be scratched. Recognizing this is the first step in a rehab plan.

The study “Impulsivity and Parkinson’s disease: More than just disinhibition,” published in the Journal of the Neurological Sciences, provides an excellent discussion of the topic, as does the chapter “Impulse Control Disorders,” by Valerie Voon and Susan Fox, in the book “Parkinson’s Disease: Diagnosis and Clinical Management.” These authors point out that PD and the medications used to treat it directly affect the neural pathways used to regulate attention and impulse control. Any type of impulse can be affected.

Those with poor impulse control prior to PD onset were more likely to have more severe impulse control problems after PD onset. The contrary also is true. Those who practiced impulse control were less impacted. Our rehab to deal with impulsivity needs the daily practice of impulse control.

The above graphic is a representation of the cognitive pathways involved and the checkpoints we can become mindful of when developing a rehabilitation plan to address impulsivity. The arrows represent the flow of data or information into our brain (from left to right).

The first place we can begin our impulse control practice is with trigger management. In my first column for Parkinson’s News Today, I mentioned my problems with ice cream. It’s a love-hate relationship: I love it while my body hates it. Put a pint of Ben & Jerry’s in the fridge and I will devour it before the day is out. It’s the itch that must be scratched. The solution: Don’t put that ice cream in the fridge. This is called trigger management — the removal of the thing that triggers the impulse. This is step one in the rehab plan to deal with impulsivity.

Step two is impulse checkpoint awareness and adjustment. There are three checkpoints, and all three affect the perception of information coming into our brains. Thus, they affect impulsivity.

Checkpoint one is a background noise filter. Our brains don’t consciously process everything that the senses pick up. Think of all the noises, sights, and smells that are around you every day. Normally, you do not attend to them all and do not remember them all. Your brain filters them.

I think that PD (and medications) affect this filter. For me, subtle sensory stimuli have become heightened, and normal stimuli can take on an exaggerated importance. Sounds from a creaking house seem louder and more threatening, and shadows seen through the corner of my eye seem like someone moving. The startle response in me can become triggered as if a gun went off nearby.

This startle information is sent to checkpoint two and given emotive character, or a perception of danger in the home. Now the fight-flight response is added to the character of the signal.

The data signal has been heightened twice before getting to the last intervention checkpoint prior to becoming impulsive action. This is checkpoint three and it is tied to scenario looping. Step three in the rehab plan involves applying scenario looping for thought inputs that can moderate the need to scratch that itch. This can be done through various brain training practices.

My next column will address brain training practices in connection with impulsivity. What issues have you had with impulse control and what is your strategy to deal with them?

***

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.

https://parkinsonsnewstoday.com/2018/11/09/parkinsons-impulsivity-itch-that-must-be-scratched/

Lack of Research and Way of Measuring Visual Hallucinations in Parkinson’s Hinders Its Treatment, Study Says

NOVEMBER 9, 2018 BY JOANA CARVALHO 

Research into the best ways of managing visual hallucinations in patients with Parkinson’s disease over the long term is severely limited and affecting treatment, a review study has found.

In particular, the lack of a universal rating scale renders data interpretation and comparison between studies difficult. To overcome this limitation, researchers propose the creation of a specific scale suitable to monitoring the effects of pharmacological and non-pharmacological treatments for visual hallucinations.

The study, “Management of visual hallucinations in dementia and Parkinson’s disease,” was published in International Psychogeriatrics.

Visual hallucinations — seeing something that is not real — is a common symptom of Parkinson’s and other types of dementia, including Alzheimer’s disease, dementia with Lewy bodies and frontotemporal dementia. These symptoms can be quite disturbing for patients, and are associated with rapid cognitive decline and increased mortality.

Although a large number of pharmacological and non-pharmacological therapies have been proposed to treat such hallucinations, an optimal management strategy is yet to be found.

This systematic review examined the prevalence and risk factors of visual hallucinations, as well as rating scales and therapeutic approaches that have been proposed to monitor and minimize their occurrence.

After a thorough literature search in the PubMed database, a total of 89 relevant studies (11 meta-analyses, 34 randomized controlled trials, six other trials, and a number of relevant review articles) were selected.

Previous studies estimated the prevalence of visual hallucinations for Alzheimer’s disease to range from 3% to 76%, and from 22% to 38% in people with Parkinson’s disease.

The high variability in prevalence, especially in Alzheimer’s disease “may be due to the setting of the study population (clinic vs. nursing home) and differences in who the informant is; whether patient, relative, or professional,” the researchers wrote.

Among Parkinson’s patients, the biggest challenge to determining prevalence of visual hallucinations seems to be separating “the contribution of dopaminergic and anticholinergic drugs from that of the disease.”

In dementia with Lewy bodies and frontotemporal dementia patients, prevalence is estimated to be 15-20% and 14.4%, respectively.

Non-pharmacological strategies have been proposed mainly as a first-line treatment for visual hallucinations. However, solid evidence from controlled trials that might demonstrate therapeutic benefit specifically for visual hallucinations is lacking.

“[R]eviewers have recommended increased socialization, as well as improving lighting and reducing visual triggers, but admit this because they are useful and inexpensive rather than based on trial evidence,” the researchers wrote.

Antipsychotics — both typical and atypical — are commonly used to treat psychosis and depression, but when used in patients with dementia are associated with a series of adverse side effects, including increased risk of stroke and death. Still, these medicines may continue to be prescribed off-label to these patients, mostly due to a lack of better alternatives.

In Parkinson’s disease, several antipsychotic treatments have been tested over the last few years. While some, like melperone and Zyprexa (olanzapine), clearly failed to ease psychosis and delusions, Clozaril (clozapine) and Nuplazid (pimavanserin) were seen to treat psychosis and hallucinations without impairing patients’ motor functions. The effects of others, like Seroquel (quetiapine), vary substantially across studies and are difficult to interpret.

In any case, these medications — even Nuplazid, the only medication approved by the U.S. Food and Drug Administration (FDA) for Parkinson’s delusions and hallucinations — “still carry the same black box warning as other antipsychotics for older people with dementia” and should be used with caution.

One of the key limitations encountered by the researchers that affects not only data interpretation, but also its generation, was the lack of a specific universal rating scale to assess visual hallucinations. Rather, symptoms tend to be “grouped together as all ‘hallucinations’ or ‘psychosis’. This over simplifies symptoms and prevents an understanding of what treatments may or may not work,” they said.

“We recommend the development of a specific scale suitable for natural history and treatment studies of VH, and for larger multi-site studies of both non-pharmacological and pharmacological treatments for VH [visual hallucinations],” the researchers concluded.

https://parkinsonsnewstoday.com/2018/11/09/lack-of-research-way-of-measuring-visual-hallucinations-in-parkinsons-hinder-treatment-study-says/

Mutations on NUS1 Gene Can Significantly Raise Person’s Risk of Parkinson’s, Study Reports

 NOVEMBER 9, 2018 BY ALICE MELÃO 

Mutations affecting the NUS1 gene are linked to a significantly increased risk — 11 times higher — of developing Parkinson’s disease, study shows.

The study, “Coding mutations in NUS1 contribute to Parkinson’s disease,” was published in Proceedings of the National Academy of Sciences.

Although exact triggers of Parkinson’s disease remain unclear, aging, and environmental and genetic factors are believed to be major culprits.

SNCA was the first gene to be linked to the development of Parkinson’s. Since its discovery in 1997, scientists have attempted to find other genes that may also play a role.

Chinese researchers conducted a detailed genetic analysis of samples collected from 39 patients with early-onset Parkinson’s disease, their parents, and 20 unaffected siblings, aiming to detect de novo mutations associated with the disease.

A de novo mutation is a genetic alteration evident for the first time in one family member as a result of a mutation in the egg or sperm of a parent, or a mutation that arises in the fertilized egg itself during early development. A child with a de novo (new) mutation will develop the associated disease, while his parents or siblings will not.

Researchers identified 12 genes carrying de novo mutations — MAD1L1, NUP98, PPP2CB, PKMYT1, TRIM24, CEP131, CTTNBP2, NUS1, SMPD3, MGRN1, IFI35, and RUSC2. These genes are known to be expressed in two brain regions affected in Parkinson’s disease, called the stratum and substantia nigra, and could be functionally relevant to early-onset Parkinson’s.

Biologic network analysis showed that all the identified genes may share similar biological functions, and act together to increase the risk of developing Parkinson’s.

Patients did not have any other genetic variants previously associated with the disease.

Next, researchers explored the presence of rare mutations in these 12 genes in samples collected from 1,852 patients with sporadic (non-familial) Parkinson’s disease and 1,565 healthy volunteers. In this secondary screening, no significant alterations were found with exception of the NUS1 gene.

To confirm this finding, the team performed a detailed analysis of the NUS1 gene in a larger number of samples (3,237 patients and 2,858 controls). Similar to the previous analysis, Parkinson’s patients carried NUS1 mutations that were not present in the (healthy) control samples.

The presence of NUS1 variants, and consequent lower levels of the gene, were associated with a 11.3 times higher risk of having Parkinson’s disease.

Researchers also examined the role of the NUS1 gene in vivo, by deleting the equivalent gene — which shares 44% similarly with the human NUS1 — in a fly model (Drosophila). They observed that this deletion induced the loss of dopamine-producing nerve cells and, consequently, lower brain dopamine levels — two main hallmarks of Parkinson’s disease.

“These data … suggest that NUS1 plays important roles in dopamine neurons and that the loss of NUS1 could lead to neuronal dysfunction that is related to Parkinson’s disease,” the researchers wrote.

“[D]e novo mutations could contribute to early onset PD [Parkinson’s disease] pathogenesis and identify NUS1 as a candidate gene for PD,” they concluded.

https://parkinsonsnewstoday.com/2018/11/09/nus1-gene-mutations-linked-to-significantly-higher-risk-of-parkinsons-disease-in-study/

Scientists confirm the role of 'molecular switch' in Parkinson's disease

November 9, 2018     By Catharine Paddock PhD

Scientists have confirmed that a protective cell mechanism can be disrupted in the brains of people with Parkinson's disease. The mechanism protects cells against damage caused by faulty mitochondria, the small power units that produce cells' energy.

Researchers confirm that in Parkinson's, a faulty molecular switch triggers the degeneration of neurons.

In the past week, the journal Open Biology published a report on the recent findings.

Parkinson's is a brain disease that worsens over time. As it progresses, it makes talking and walking more difficult, and it can also affect behavior, sleep, thinking, and memory. Other symptoms include fatigue and depression.

The disease arises from the loss of dopamine-producing cells in the brain.

Dopamine is a brain chemical that, among other things, helps control motor function. This is why movement becomes increasingly disrupted as more dopamine cells stop working or die.

Symptoms rarely appear in people younger than 60. However, in 5–10 percent of individuals with Parkinson's, symptoms occur before the age of 50.

Most forms of early-onset Parkinson's disease tend to be inherited, and some are associated with gene mutations.

In the United States, about 60,000 people learn that they have Parkinson's every year, and almost 1 million people in the country will be living with the disease by 2020.

PINK1-Parkin switch operates in the brain

There is no cure for Parkinson's disease, and scientists do not know exactly what causes the loss or impairment of dopamine cells.

The disease likely results from a combination of genetic and environmental factors.

Research has already shown that when an enzyme called PINK1 detects defective mitochondria in cells, it switches on another enzyme, called Parkin. This results in the disposal of faulty mitochondria, and it protects the cells.

Some people with early-onset Parkinson's disease have mutations in the genes that code for PINK1 and Parkin.

Before the recent study, it was unclear whether the PINK1-Parkin switch occurred in the brain. Also, scientists were unsure whether the switch was disrupted in people with Parkinson's disease.

Using genetically modified mice, researchers at the University of Dundee in the United Kingdom, together with colleagues at other European centers, confirmed that the PINK1-Parkin switch operates in the brain.

The researchers then identified two people who had developed an early-onset form of Parkinson's disease. By testing their cells, the team confirmed that these individuals had a defective version of the PINK1-Parkin switch.

The two participants also had the same rare genetic mutation that produces the faulty molecular switch.

Findings support drug-targeting of enzymes

Study co-author Miratul Muqit, a professor in the School of Life Sciences at the University of Dundee, is grateful to the collaborators who "helped identify these rare patients who have helped us finally answer this question."

Researchers at the University of Helsinki in Finland tracked down one individual, and the other was identified in a study organized by the Michael J. Fox Foundation in the U.S.

"The probability of finding rare patients with the critical mutation to test in the lab was as low as 1 in 3 billion," Prof. Muqit explains.

The mutation occurs in a precise location of the gene that codes for Parkin, and it prevents PINK1 from being able to switch Parkin on.

The team expects that the study will spur further research into the molecular switch and the development of drugs to activate it.

There is currently great interest to directly target PINK1 and Parkin as a potential therapy against Parkinson's, and this study strongly backs the rationale of this approach."

Prof. Miratul Muqit

https://www.medicalnewstoday.com/articles/323634.php 

Monkey gaze study shows dopamine's role in response inhibition

November 9, 2018, University of Tsukuba

Monkey Gaze Study Shows Dopamine's Role in Response Inhibition. Credit: University of Tsukuba

University of Tsukuba researchers report the importance of the brain's dopaminergic system for inhibiting already-planned actions. They trained monkeys to redirect their gaze toward targets presented on a screen, apart from when presented with signals to avoid such redirection. Simultaneous analysis showed that the activity of dopaminergic neurons correlated with successful refusal to redirect gaze to a new target. These findings could aid the development of treatments for diseases with impaired inhibition such as Parkinson's.

Among the diversity of behaviors implemented by the brain, the prevention of actions that might be beneficial in a certain context, but counterproductive or harmful in another, is particularly important. Some insights into how the brain achieves this have been obtained, but much remains unclear, including the involvement of the neurotransmitter dopamine. Shedding light on this would explain much about how behavioral control is achieved, and could help treat diseases in which inhibition of certain actions is impaired.

In a study involving analyses of gaze fixation and the visual tracking of targets in rhesus monkeys, researchers at University of Tsukuba have shown that the brain's dopamine system is key to the subsequent inhibition of actions that have already been planned.

In this work, reported in the journal Neuron, the team placed two monkeys in front of a computer screen and, using the provision of reward in the form of drinks, trained them to direct their gaze at targets on the screen presented in different patterns. The monkeys were trained to redirect their attention away from the center of the screen to another target in 70 percent of the trials, but to resist the temptation to do this in 30 percent of the trials when signaled to do so.

Via visual scans using an infrared eye-tracking system, the researchers also measured neuronal attention at single-neuron resolution while the monkeys looked at the screen. The researchers recorded approximately 40 dopamine-related neurons in each of the monkeys, and analyzed the correlations between their activities and success or failure in resisting redirecting their gaze to a new target in the 30 percent of trials.

"Using this experimental setup, we found that these dopaminergic neurons tended to be active when the monkeys successfully resisted the urge to redirect their gaze," Masayuki Matsumoto says. "We then confirmed that it was the dopaminergic system that caused this response inhibition by injecting drugs that block dopaminergic neurotransmission."

The team's findings reveal details about the specific brain regions and neurological pathways involved in this response inhibition, showing that dopaminergic neurons in the substantia nigra as well as striatal neurons are key to canceling a previously planned action. The duration of the pause between the initial command and the subsequent inhibitory counter-command also influenced the monkeys' success in the trials, providing hints about the mechanisms involved.

"Now that we know more about how preplanned actions are inhibited in the brain, we may be able to develop treatments for conditions involving impaired inhibition, such as Parkinson's disease," says lead author Takaya Ogasawara.

More information: Takaya Ogasawara et al, Primate Nigrostriatal Dopamine System Regulates Saccadic Response Inhibition, Neuron (2018).  DOI: 10.1016/j.neuron.2018.10.025 

Among the diversity of behaviors implemented by the brain, the prevention of actions that might be beneficial in a certain context, but counterproductive or harmful in another, is particularly important. Some insights into how the brain achieves this have been obtained, but much remains unclear, including the involvement of the neurotransmitter dopamine. Shedding light on this would explain much about how behavioral control is achieved, and could help treat diseases in which inhibition of certain actions is impaired.

In a study involving analyses of gaze fixation and the visual tracking of targets in rhesus monkeys, researchers at University of Tsukuba have shown that the brain's dopamine system is key to the subsequent inhibition of actions that have already been planned.

In this work, reported in the journal Neuron, the team placed two monkeys in front of a computer screen and, using the provision of reward in the form of drinks, trained them to direct their gaze at targets on the screen presented in different patterns. The monkeys were trained to redirect their attention away from the center of the screen to another target in 70 percent of the trials, but to resist the temptation to do this in 30 percent of the trials when signaled to do so.

Via visual scans using an infrared eye-tracking system, the researchers also measured neuronal attention at single-neuron resolution while the monkeys looked at the screen. The researchers recorded approximately 40 dopamine-related neurons in each of the monkeys, and analyzed the correlations between their activities and success or failure in resisting redirecting their gaze to a new target in the 30 percent of trials.

"Using this experimental setup, we found that these dopaminergic neurons tended to be active when the monkeys successfully resisted the urge to redirect their gaze," Masayuki Matsumoto says. "We then confirmed that it was the dopaminergic system that caused this response inhibition by injecting drugs that block dopaminergic neurotransmission."

The team's findings reveal details about the specific brain regions and neurological pathways involved in this response inhibition, showing that dopaminergic neurons in the substantia nigra as well as striatal neurons are key to canceling a previously planned action. The duration of the pause between the initial command and the subsequent inhibitory counter-command also influenced the monkeys' success in the trials, providing hints about the mechanisms involved.

"Now that we know more about how preplanned actions are inhibited in the brain, we may be able to develop treatments for conditions involving impaired inhibition, such as Parkinson's disease," says lead author Takaya Ogasawara. 

More information: Takaya Ogasawara et al, Primate Nigrostriatal Dopamine System Regulates Saccadic Response Inhibition, Neuron (2018).  DOI: 10.1016/j.neuron.2018.10.025 

Journal reference: Neuron

Provided by: University of Tsukuba 

https://medicalxpress.com/news/2018-11-monkey-dopamine-role-response-inhibition.html

Scalpel-free surgery enhances quality of life for Parkinson's patients, study finds

November 9, 2018, University of Virginia

The improvement in a patient's hand tremor is checked during a focused ultrasound procedure. Credit: Harry Moxley | University of Virginia Health System

A high-tech form of brain surgery that replaces scalpels with sound waves improved quality of life for people with Parkinson's disease that has resisted other forms of treatment, a new study has found.

Further, the University of Virginia School of Medicine researchers conclude their study offers "comprehensive evidence of safety" in terms of the approach's effect on mood, behavior and cognitive ability, areas largely neglected in previous research.

"In our initial study that looked at the outcomes of focused ultrasound surgery in Parkinson's disease, we primarily described post-operative improvements in motor symptoms, specifically tremor," said Scott Sperling, PsyD, a clinical neuropsychologist at UVA. "In this study, we extended these initial results and showed that focused ultrasound thalamotomy is not only safe from a cognitive and mood perspective, but that patients who underwent surgery realized significant and sustained benefits in terms of functional disability and overall quality of life."

Focused Ultrasound and Parkinson's Disease

Focused ultrasound, as the procedure is known, has already been approved by the federal Food and Drug Administration for the treatment of essential tremor, the most common movement disorder. That approval came after a pioneering international study led by UVA neurosurgeon Jeff Elias, MD. He and his colleagues have since demonstrated the technology's potential in reducing tremor in people with drug-resistant Parkinson's disease. The goal is to use focused sound waves to interrupt the faulty brain circuits responsible for the uncontrollable shaking associated with the disease.

The new study looked at the effects on 27 adults, all with severe Parkinson's tremor that had not responded to previous treatment. The study participants were initially divided into two groups. Twenty received the procedure, while seven received a fake procedure, to serve as a control group. (The seven in the control group were later offered the opportunity to receive the real procedure, and all but one did.)

After receiving the procedure, study participants reported improved quality of life at both three months and 12 months. "After surgery, patients experienced significant improvements in multiple aspects of quality of life, including their ability to perform simple daily tasks, emotional well-being and the sense of stigma they experienced due to their tremor," Sperling said. "Our results suggest that post-operative improvements in tremor lead to very meaningful improvements in day-to-day functioning and, subsequently, to better overall quality of life."

University of Virginia Health System neurosurgeon Jeff Elias, MD, is seen in front of the MRI used to "see" inside patients' brains during focused ultrasound surgery. The MRI imaging helps him target just the right spot to disrupt faulty brain circuits that cause tremor. Credit: University of Virginia Health System

The Effects on Mood and Memory

The study was notable for its in-depth examination of the psychological and cognitive effects of the procedure, areas that have received relatively little attention in previous research.

The researchers found that mood and cognition, and the ability to go about daily life, ultimately had more effect on participants' assessment of their overall quality of life than did their tremor severity or the amount of tremor improvement seen after the procedure.

"A person's perception of their quality of life is shaped in many different ways," Sperling said. "Mood and behavioral symptoms, such as depression, anxiety and apathy, often have a greater impact on quality of life than the measurable severity of one's tremor."

The only cognitive declines seen in participants followed through the study were in how quickly they were able to name colors and think of and speak words. The cause of this was unclear, though the researchers suggested this could be a result of the natural progression of Parkinson's. (Focused ultrasound is being tested to address the tremor associated with the disease, not its other symptoms.)

The researchers noted that their study was limited by its small size and the fact that participants' medication dosing varied, among other factors.

To become available as a treatment for medication-resistant Parkinson's, the approach would need approval from the FDA. UVA's new research is an important step in that process.

The researchers have published their findings in the scientific journal Neurology.

More information: Scott A. Sperling et al, Focused ultrasound thalamotomy in Parkinson disease, Neurology(2018).  DOI: 10.1212/WNL.0000000000006279 

Journal reference: Neurology

Provided by: University of Virginia 

https://medicalxpress.com/news/2018-11-scalpel-free-surgery-quality-life-parkinson.html

World-first pill may stop Parkinson’s

John Elder  Nov 8, 2018

A new therapy that appears to stop Parkinson’s disease “in its tracks” will begin phase-one clinical trials in humans next year.

The therapy, developed by researchers at the University of Queensland – and partly under-written by the Michael J Fox Foundation – is a world first because it stops the death of brain cells in Parkinson’s sufferers rather than managing symptoms.

If human trials echo the stunning results in animal testing, the inflammation of the brain that causes so much of the progressive damage in Parkinson’s disease (PD) could be halted by taking a single pill each day.

UQ Faculty of Medicine researcher Associate Professor Trent Woodruff said the key to the new therapy is a small molecule, MCC950 – a compound developed and abandoned 10 years ago by a big pharma company that didn’t understand how it actually worked.

At that stage, though, inflammation in the Parkinson’s brain was less well understood.

https://youtu.be/kL5fIhejxxE

Parkinson’s disease, said Dr Woodruff, is characterised by the loss of brain cells that produce dopamine, a chemical that co-ordinates motor control – and it’s the loss of dopamine that has been the focus of treatment. But it is also accompanied by this chronic inflammation that occurs as an immune response gone haywire.

It works like this: Inflammation is activated in our cells by complex proteins called inflammasomes. About five years ago, Dr Woodruff and his team found that the immune system causes the NLRP3 inflammasome to light up in Parkinson’s patients, with signals found in the brain and even in the blood.

They then found that the tiny molecule MCC950, given orally once a day, in experiments with mice, “blocked NLRP3 activation in the brain and prevented the loss of brain cells, resulting in markedly improved motor function”.

UQ Institute for Molecular Bioscience researcher Professor Matt Cooper – who initially experimented with MCC950 in the treatment of an auto-inflammatory disease called Muckle-Wells syndrome that can cause deafness and kidney failure – said drug companies had traditionally tried to treat neurodegenerative disorders by blocking neurotoxic proteins that build up in the brain and cause disease.

“We have taken an alternative approach by focusing on immune cells in the brain called microglia that can clear these toxic proteins,” he said.

“With diseases of ageing such as Parkinson’s, our immune system can become over-activated, with microglia causing inflammation and damage to the brain.”

The NLRP3 inflammasome (green) is expressed by immune cells (red) in the brains of people with Parkinson’s disease. Photo: University of Queensland

He said MCC950 effectively “cooled the brains on fire”, turning down microglial inflammatory activity, and allowing neurones to function normally.

This was achieved with three different models of Parkinson’s on mice. It took a further two years of tests in order to convince the editors of the prestigious journal Science Translational Medicine of the efficacy of treatment. The researchers’ paper was published on October 31.

The progress of MCC950 to market appears to be happening rather quickly. Both the Michael J Fox Foundation for Parkinson’s Research and the Ireland-based drug company Inflazome are keen for human trials to start as soon as possible.

Dr Woodruff said much of the preclinical work was already completed.

The biggest hurdle, apart from funding, is that MCC950 came off a patent. This means the researchers have had to develop variations of the original drug for intellectual property reasons. Those new drugs are currently being tested and, according to Dr Woodruff, proving to be even more effective.

There are 10 million people with Parkinson’s disease worldwide. They still have a few years to wait and see if the magic in the lab can be replicated in people.

The phase-one tests next year will determine whether or not the drug is safe in healthy people. All going well, volunteers with Parkinson’s will be recruited for phase-two testing in 2020.

Whether Michael J Fox himself will be one of those volunteers is not yet known.

https://thenewdaily.com.au/life/wellbeing/2018/11/08/michael-j-fox-parkinsons-therapy/