Monthly Research Review – May 2018

~ Simon

At the end of each month the SoPD writes a post which provides an overview of some of the major pieces of Parkinson’s-related research that were made available during May 2018.

The post is divided into five parts based on the type of research (Basic biology, disease mechanism, clinical research, other news, and Review articles/videos). 

Before we start: 

Today is the 31st May 2018, which represents the one year anniversary since the passing of Tom Isaacs:

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Tom was one of the co-founders of the Cure PD Trust.

In 1996 – at just 27-years of age – Tom, a London-based surveyor, was diagnosed with Parkinson’s. After dealing with the initial shock of it all, Tom embraced his situation and became a committed, (utterly) tireless activist. He firstly walked the entire coastline of the UK to raise money and awareness for Parkinson’s.

tom isaacs

His book, “Shake well before use“, discusses that trip and adapting to life with Parkinson’s. It is a fantastic read. Upon returning from his epic walk, he (along with three others) founded and set up the Cure Parkinson’s Trust.

It is pretty safe to say that other than Michael J Fox and Muhammad Ali, Tom has had the most impact on marshaling scientific research efforts to find a cure for Parkinson’s.

And he did it all with style and humour:

This was a video of Tom in 2009, talking about life with Parkinson’s disease:

Here at SoPD HQ, we were gutted by his passing, and wanted to make a special note here.

 

So, what happened during May 2018?

In world news:

May 3rd – The 2018 lower Puna eruption began, causing destruction of property and forcing many citizens of Hawaii to evacuate as lava flowed across the land.

May 8–12th – The Eurovision Song Contest 2018 is held in Lisbon, Portugal…. and I for one really don’t care who won!

May 19th – Prince Harry married Miss Meghan Markle is held at St George’s Chapel (Windsor, England) in front of an estimated global audience of 1.9 billion.

And finally, on May 12th – There was a strange survey online to determine whether people hear “Yanny or Laurel” when playing the following track:

Apparently 53% of over 500,000 people answered on a Twitter poll that they heard a man saying the word “Laurel” (seriously, who has this kind of time to waste?!?)

The top 5 pieces of Parkinson’s news

1. New method of assessing brain activity:

Researchers have developed a new method of monitoring thousands of cells in mouse model of Parkinson’s (before & after dopamine depletion, & during L-DOPA-induced dyskinesia). Using the Inscopix brain imaging platform, they revealed patterns of abnormal brain activity that may produce the motor deficits in Parkinson’s ( to read more about this, click here to read the editorial, and Click here to read the press release).

2. Different types of cells have different types of aggregates

The Parkinson’s-associated alpha synuclein clusters (or aggregates) in glial cells are conformationally & biologically distinct from the Lewy bodies found in neurons. Different strains of alpha synuclein protein are determined by both misfolded seeds AND intracellular environments ( to read more and click here to read the press release).

3. An update on the vaccine of Parkinson’s

Austrian biotech company AFFiRiS has announced long-term data from their first-in-human clinical studies of AFFITOPE PD01A which targets the toxic (oligomeric) form of alpha synuclein in early Parkinson’s. The vaccine was found to be safe and well tolerated for the 4 year period of the study. In addition the press release suggested that ‘clinical scores were stable for the entire study period’, though study not designed for efficacy ( to read the research report and click here to read a SoPD post on this topic).

4. TB, PD and LRRK2

UK researchers found that Parkinson’s‐associated LRRK2 affects innate immune control of tuberculosis infections. The researchers found that by reducing levels of LRRK2, they reduced the rate at which TB could infect cells and animals. Unexpected result perhaps, but as a result, LRRK2 inhibitors which are being developed for Parkinson’s could also be tested on TB (1/4 of world pop. infected) ( to read more about the research, click here to read the press release, and click here to read a SoPD post on the topic).

5. More on LRRK2: Mutations disrupt the packaging of dopamine

Researchers found that mutations in Parkinson’s-associated LRRK2 gene lead to impaired synaptic vesicle packaging of dopamine & the eventual buildup of dopamine, which is rapidly oxidized & becomes toxic ( to read the research report and click here for the press release).

Basic biology news

  • Rats with Parkinson’s-associated PINK1 genetic variations show early-onset swallowing issues, which correlative with changes in the brainstem – useful new tool for investigating mechanisms & treatment of dysphagia (problems swallowing –  to read more about this).
  • NIH researchers described a new method of detecting the level of activity (autophosphorylation) of Parkinson’s-associated protein S1292 LRRK2 in tissue – could be a useful readout for the protein activity in clinical trials ( to read the research report).
  • Parkinson’s-associated alpha synuclein protein fibrils reduce the density of postsynaptic spines, but increase frequency of postsynaptic currents and presynaptic docked vesicles, suggesting enhanced presynaptic function ( to read more about this).

  • Arbutus unedo (the strawberry tree) produces (poly)phenol-digested metabolites that effectively counteracted Parkinson’s-associated alpha synuclein toxicity in yeast & human cells, improving viability by reducing a-syn aggregation & inducing its clearance ( to read more about this).
  • German researchers provide a very thorough analysis of the structural and kinetic features of Parkinson’s-associated protein alpha synuclein to better understand the molecular determinants of alpha synuclein–membrane association ( to read more about this).
  • Harvard University researchers have developed new technique to analyse (in unprecedented detail) how cells initiate removal of damaged mitochondria. Interesting analysis of Parkinson’s-associated PINK & Parkin protein functions ( to read the abstract of this research and click here for the press release).
  • Salidroside, a compound used in traditional Chinese medicine, has been found to be neuroprotective in a cell model of Parkinson’s ( to read this research report).
  • Researcher demonstrate the neuroprotective effects of Sodium hydrosulfide in a rodent model of Parkinson’s. Curiously it has no effect on the superoxide dismutase & glutathione peroxidase activity (Click here to read the abstract of this research report).
  • Researchers find that the activity of glial GAT-3 transporters in an area of the brain called the globus pallidus may contribute to abnormal motor coordination in Parkinson’s. Blocking GAT-3 activity in normal rats disrupts motor coordination ( to read more about this research).

  • International team have found that cholesterol may act as a catalyst that triggers formation of toxic amyloid-beta protein aggregates in the development of Alzheimer’s. Does same apply to Parkinson’s? ( to read more and click here for the press release).
  • Genetic mutations in the LRRK2 & VPS35 genes result in rare forms of Parkinson’s. New research finds that VPS35 controls LRRK2 activity & that VPS35[D620N] mutation results in a gain of function causing hyperactivation of LRRK2 kinase ( to read this research report).
  • Recently high levels of the small GTPase Rab7 were found to induce clearance of Parkinson’s-associated alpha synuclein aggregates. Now researchers find that “FYVE and coiled‐coil domain‐containing protein 1” (FYCO1) is an effector of Rab7 ( to read more about this).
  • Dysfunction in cholinergic neurons in the brain is believed to be involved with some of the motor issues occurring in Parkinson’s. New findings on the role of these cells & how dopamine may affect them ( to read the abstract of this research).
  • Researchers treated the cells with 598 pairs of transcription factors, & found 76 pairs that can induce mouse connective-tissue cells to adopt a neuron-like identity in vitro – another step closer to personalised approaches for Parkinsons? ( to read more about this and click here to read the editorial about this research).
  • Molecular modelling, mass spectrometry & radioligand studies have been conducted on Parkinson’s-associated alpha synuclein fibrils, revealing the presence of 3 different binding sites capable of binding small molecules with moderate to high affinity ( to learn more about this).
  • A new biorxiv manuscript presents the Virtual Metabolic Human () database holds all current knowledge of human metabolism within 5 interlinked resources: metabolism, microbiome, disease, nutrition, & “ReconMaps”. Links human metabolism and Parkinson’s ( to read the manuscript).

  • Anti-mitophagic control by TP53 – TP53 is a tumor suppressor gene that also plays a role in cell death. New research suggests that it also reduces the removal of sick/old mitochondria by the transcriptional repression of Parkinson’s associated gene PINK1 ( to read more about this).
  • Cold shock protein RBM3 has been shown to mediate protection in models of Alzheimer’s. Now researchers demonstrate that it can also provide neuroprotection in a cell model of Parkinson’s ( to read the research report).
  • New manuscript on BioRxiv outlines experiments involving molecular dynamics simulation to characterise influences of Parkinson’s-associated genetic mutations of alpha synuclein on amyloid formation ( to read the manuscript).
  • Researchers demonstrate that inhibition of the GTPase activating protein, TBC1D5, can enhance the activity of Rab7a – which has been identified as a potential therapeutic pathway for Parkinson’s ( to learn more about this).
  • Nuclear factor kappa B (NF-κB) regulatory protein A20 critically controls microglia activation & inhibits inflammasome-dependent neuroinflammation in models of Multiple Sclerosis. This result could have implications for Parkinson’s ( to read more about this).
  • New data demonstrates that Parkinson’s-associated PARKIN & PINK1 do actually have a crucial role for in mitophagy. In an age-dependent manner in flies at least. “‘basal’ mitophagy in the fly is strongly induced by normal aging” ( to read the research report).

 

Disease mechanism

  • Chronic, systemic treatment of calcium channel blocker isradipine alters substantia nigra dopamine neurons in a way that may diminish their vulnerability to the mitochondrial & autophagic stress observed in Parkinson’s ( to read this research report).
  • The hypothalamus acts as a central biological clock for the body. Researchers have found changes specific to different neurodegenerative conditions (Parkinson’s, multiple system atrophy & progressive supranuclear palsy) in the hypothalamus. Interestingly, changes were found in the suprachiasmatic nucleus but not in the pineal gland in Parkinson’s & PSP, while both structures were preserved in MSA ( to read more about this).
  • There are currently >30 known amyloid-associated disorders, including Parkinson’s. Researchers have investigate whether generic amyloid polyphenolic inhibitors such as Epigallocatechin gallate (EGCG) & tannic acid inhibit amyloid-like fibrillation ( to read this research report).

  • Researchers report Lewy body-like inclusions of Parkinson’s-associated alpha synuclein protein triggering reactive microglia activity prior to nigral degeneration in rodent model of PD ( to read the research report).
  • Interesting new manuscript on biorxiv looking at how a protein called ‘Engrailed’ blocks degeneration in adult dopamine neurons through blocking LINE-1 (a retrotransposon). Long INterspersed Elements (LINEs) transposons comprise ≈ 21% of the human genome. They are sections of DNA that can change position within the genome. Most are inactive. Is engrailed a potential therapeutic target for Parkinson’s? ( to read the manuscript).
  • researchers discover a novel interaction between two Parkinson’s-linked proteins (LRRK2 and Auxilin), which results in synaptic dysfunction & contributes to dopamine-mediated toxicity in patient-derived dopaminergic neurons ( to read more about this).
  • High levels of mutant alpha synuclein protein causes Parkinson’s-like pathology in neurons & glial cells in the in locus coeruleus of mice – another region of the brain affected by PD ( to read more about this).
  • New evidence that Parkinson’s-associated alpha synuclein causes cell death (apoptosis) in astrocytes by causing dysfunction of the endoplasmic reticulum‑Golgi compartment (the production-line for proteins –  to learn more about this).
  • New research demonstrates the importance of the mitochondrial response when challenged with an environmental stressor. A metabolite from soil bacterium, Streptomyces venezuelae, causes an increase in mitochondrial fragmentation in a Parkinson’s model ( to read more about this).
  • New study finds Parkinson’s-associated protein alpha synuclein can be transported from the mouse gastrointestinal tract to the brainstem via the vagus nerve, but (like other studies) the effect is transient. Lewy body like structures do not spread in brain ( to read more about this).

  • Could the balance of astrocytes & microglia within the midbrain be a key factor underlying the selective vulnerability of different populations of dopamine neurons in Parkinson’s? New research shows VTA astrocytes mediate protection of dopamine neurons ( to read more about this).
  • French researchers studied the effect of xenon inhalation on gait & posture problems in a primate model of Parkinson’s with levodopa‐induced dyskinesia. Xenon alleviated dyskinesias without compromising the benefit of L-dopa ( to learn more about this).

Be warned: Xenon can be toxic and it should not be consumed without medical supervision. Do NOT try this at home alone.

  • Researchers show that Parkinson’s-associated LRRK2 protein binds & modulates actin remodelling protein WAVE2 specifically in myeloid (blood) cells. Lrrk2–G2019S mutation results in WAVE2-mediated increase in phagocytosis & dopamine cell death ( to read more about this).
  • Researchers perform biochemical profiling to identify & quantify 71 metabolites in brain & 182 in blood from a mouse model of Parkinson’s. Taurine & hypotaurine metabolism was the major pathway found to be significantly perturbed in the brain ( to read more about this).
  • New research finds that Nicotinamide adenine dinucleotide phosphate (NADPH), which is important for maintaining the level of glutathione, protects dopamine neurons in a model of Parkinson’s ( to read the research report).
  • Researchers find that Parkinson’s-associated alpha synuclein binds to MAO‐B & stimulates its enzymatic activity leading 2 cell loss (via AEP activation). Mutant alpha synuclein induces PD pathogenesis in wild‐type, but not MAO‐B knock out mice ( to read more about this).
  • Continuously giving mice caffeine in their drinking water for 120 days (did they even sleep?) protects them against an alpha synuclein-based model of Parkinson’s; caffeine helps to reestablish autophagy activity ( to read the research report).

  • German researcher present a gene regulatory network constructed from the dysregulated genes & miRNAs in Parkinson’s. The results highlight 6 genetic driver elements (2 genes & 4 miRNAs –  to read more about this).
  • Researchers find that three domains of beta-synuclein protein together contribute to providing effective inhibition of Parkinson’s-associated alpha synuclein aggregation. Now exploring therapeutic potential ( to read more about this).
  • More evidence that granulocyte-macrophage colony-stimulating factor (GM-CSF) provides neuroprotection in models of Parkinson’s. Further support for exploring Sargramostim derivatives for Parkinson’s ( to read more about this
  • Neurotoxin-based NLRP3 inflammasome activation in microglia plays a central role in dopaminergic neurodegeneration observed in models of Parkinson’s. Administration of IL-1 receptor antagonist blocks the effect ( to read more about this).
  • Urate inhibits microglia activation to protect neurons in a model of Parkinson’s. Pretreatment with probenecid, an inhibitor of urate transporter 1 abolishes the anti-inflammatory effect of urate. Further support for the SURE-PD3/Inosine clinical trial ( to read more about this).
  • Researchers demonstrate how agrochemical exposure selectively triggers a deficit in mitochondrial transport (by nitrating the microtubules) in neurons harboring Parkinson’s-associated SNCA-A53T genetic mutation ( to read more about this and click here to read the Parkinson’s UK medium blog post on this topic).

Clinical research

  • Researchers find microRNA-based signatures in cerebrospinal fluid from 40 early stage PD subjects (& 40 well-matched controls) that could be used as potential diagnostic aids for early stage Parkinson’s ( to read more about this).
  • New research suggests increasing prevalence of Parkinson’s in Estonia – rates in oldest age‐groups have risen substantially over the last 20 years ( to read more about this).

  • Motor symptom asymmetry at the onset of Parkinson’s is very common. Now researchers have a method of brain (neuromelanin) imaging which can show asymmetry of a region affected by PD (lateral substantia nigra pars compacta), consistent with motor asymmetry ( to read more about this).
  • Rsearchers comprehensively assessed people with Parkinson’s using the Battery for the Assessment of Auditory Sensorimotor and Timing Abilities (BAASTA). Results suggest it is a consistent & reliable tool for evaluating timing & rhythm skills ( to read more about this).
  • To improve the quality of the deep brain stimulation programming for Parkinson’s in China, experts have reviewed the relevant literatures & combined their own experiences to develop an expert consensus ( to read more about this).
  • Option-generation task requires subjects to draw as many different paths as possible between two points. Researchers examine 35 people with Parkinson’s and find that dopamine plays an important role in modulating option generation ( to read the research article and click here to read the press release).
  • Israeli researchers review the use of virtual reality for rehabilitation of balance & gait in a range of medical conditions including Parkinson’s, suggesting that it brings additional benefits when combined with conventional rehabilitation ( to read the abstract of this report).

  • An electrophysiological signal has been discovered that could potentially be used for guiding electrode implantation surgery & tailoring deep brain stimulation therapy for Parkinson’s; could improve patient outcomes ( to learn more about this and click here for the press release).
  • Researchers present noninvasive brain imaging analysis techniques (PK11195‐PET) that can detect abnormal microglial activation in people with Parkinson’s. Effect size for 1 person would need to be 14% in a drug trial ( to read more about this).
  • A new model-free machine learning based techniques provide a reliable clinical outcome forecasting method for falls in people with Parkinson’s; with a classification accuracy of 70–80% ( to learn more).
  • Researchers find significant associations in France between high proportions of workers in specific industry sectors (agriculture, metallurgy, textile) and the incidence of Parkinson’s ( to read more about this).
  • Fitbit Charge & Garmin Vívosmart wrist bands went head-to-head in measuring steps & reflecting intensity of activity in Parkinson’s. Garmin device was more accurate at reflecting step count across a broader range of walking cadences than the Fitbit ( to learn more).

  • Another wearable device (wristband) for continuous monitoring of tremor & other motor symptoms in Parkinson’s. Interesting efforts to reduce the probability of discriminating between extrapyramidal symptoms & normal daily activity ( to read more).
  • Researchers propose that accumulation of alpha synuclein in the retina (of the eye) could provide an in vivo indicator of brain pathology severity, & detection of it may help in the diagnosis & monitoring of Parkinson’s progression ( to read more).
  • People with Parkinson’s who have symptoms of autonomic dysfunction show disrupted thalamo-striato-hypothalamic function independent of overall motor dysfunction, duration of condition, age & cognitive ability (Click here to read more about this).
  • Turkish researchers demonstrate structural & functional changes (based on electro-physiological & morphological analysis) in different parts of visual pathways in early-stage Parkinson’s (assessed over 6 months –  to read more about this).
  • DiGeorge syndrome (aka 22q11.2 deletion syndrome), caused by a deletion in chromosome 22. Affected people can develop Parkinson’s. New research suggests clinical characteristics & response to standard medication comparable to those in idiopathic PD.The average age at onset is earlier, and importantly, treatment of preexisting psychotic illness may actual delay diagnosis of Parkinson’s in people with DiGeorge syndrome ( to read more about this).
  •  New manuscript on Biorxiv provides “tentative evidence that the motor deficits in Parkinson’s may be partly accounted by deficits in internal monitoring of movements”. Issues in saccadic eye movements correlate w/ the integrity of dopamine system ( to read the manuscript).
  • Results of a new brain imaging technique for Parkinson’s have been published. The two reports present a potentially useful tool in diagnosing differential parkinsonian syndromes & tracking over time ( and here to learn more about this).
  • New large study suggests that in the context of standard therapy, Parkinson’s‐related psychotic disorder can remit at a frequency of approximately 27%. Akinetic‐rigid motor impairment was more strongly associated with psychosis than disease duration ( to read more about this).
  • A new biorxiv manuscript describes a multi-institutional collaborative effort to develop a comprehensive, open source pipeline for Deep Brain stimulation imaging & connectomics for Parkinson’s ( to read the manuscript).

  • Another new biorxiv manuscript also looked at Deep Brain stimulation & brain imaging for Parkinson’s. The researchers used MRI imaging & machine learning to more accurately localise the electrodes ( to read the manuscript).
  • Researchers provides further support for the importance of everyday physical activities in people with Parkinson’s. Clear relationships between activity & well‐being ( to read more about this).
  • Retrospective analysis using data collected in the DATATOP study, suggests that two copies of the BDNF rs6265 Met66 genetic variant is associated with less severity in motor symptoms & potentially a slower rate of progression in Parkinson’s ( to read more about this).
  • Prolonged use of Parkinson’s medication entacapone – the reversible inhibitor of the catechol-O-methyltransferase (COMT) enzyme that breaks down L-dopa – is not associated with prostate cancer incidence in cohort study of 17,666 U.S. male veterans ( to read more about this).
  • Greek researchers present a study of touchscreen typing-pattern analysis for detecting fine motor skills decline in early-stage Parkinson’s ( to learn more about this).
  • New brain imaging study suggests that people with Parkinson’s exhibit unique functional connectivity between the caudate & the posterior cingulate cortex, may be associated with cholinergic status & cognition ( to learn more).
  • Data from a prospective cohort study presented at the AAN Annual Meeting in April, suggests that by 7 years post diagnosis 50% of the people with REM sleep behavior disorder have developed Parkinson’s or dementia with Lewy bodies ( to learn more about this).

  • Researchers have compared eye movement preparation in individuals with sporadic Parkinson’s with people with PARKIN-associated PD & controls. In spite of increased reaction time, the influence of elapsed time on movement preparation was similar in all groups ( to read the research report).
  • Brain imaging study finds altered somatosensory processing in Parkinson’s. PD demonstrates reduced activation of somatosensory cortex & sensorimotor integration. Dopamine meds reduce the tactile-evoked activity within the motor but not somatosensory cortex ( to learn more about this).
  • Depletion of the chemical dopamine in the putamen region of the brain of newly diagnosed people with Parkinson’s predicts future development of wearing-off of medication ( to read more about this).
  • Danish researchers provide further evidence of an association between inflammatory bowel disease (IBD) & Parkinson’s. People with IBD have a 22% increased risk of developing PD, compared with non-IBD individuals ( to read more about this and click here for the press release).
  • A nationwide study of >39,000 people in Sweden with inflammatory bowel disease found a 1.3-fold increased incidence of Parkinson’s compared with the general pop. When adjusted 4 no. of health care visits, risk was reduced ( to read more about this).

  • Probable REM sleep behaviour disorder (PRBD) is associated with Parkinson’s. Lewy body pathology was found in 80/101(79.2%) cases with PRBD & only 198/501 (39.5%) without PRBD. PRBD not observed in any of 46 incidental Lewy body disease cases ( to read more about this).
  • New study finds that higher serum uric acid levels are associated with a tremor-dominant motor subtype & less fatigue in early Parkinson’s. Useful information for the SURE-PD3 clinical trial ( to read more about this).
  • Japanese researchers find that low body mass index score has a significant impact on the life prognosis of people with Parkinson’s, particularly males ( to read more about this).
  • A comparison of people with glucocerebrosidase (GBA)-associated Parkinson’s found that people with more severe GBA mutations have greater motor & non-motor issues than people with more mild GBA mutations (these did not differ from idiopathic PD) ( to read more about  this).
  • Researchers find that genetic variations in SLC2A9 & other genes involved in urate transport do not increase risk of developing Parkinson’s ( to read more about this).
  • Freezing of gait (FOG) is an issue for many people with Parkinson’s. Now researchers have developed & evaluated a system based on Microsoft Kinect to detect FOG & falling in people with PD ( to read more about this).
  • Thalamocortical dysrhythmia is a framework that neuroscientists use to explain the symptoms of neurological conditions like Parkinson’s. Now researchers have used it 2 identify brain areas that are common 2 the pathology of PD, pain, tinnitus, & depression ( to read more about this and click here for the press release).
  • In a new manuscript on bioRxiv, researchers searched 4 electronic databases of routinely-collected healthcare information to identify positive predictive values for identifying Parkinson’s ( to read the manuscript).
  • Subthalamic deep brain stimulation for Parkinson’s is associated with a statistically & clinically significant, but variable improvement in sleep. Most frequent improvements were better overall sleep quality ( to read more on this).
  • Oxidized DJ-1 levels in urine samples could be used as a putative biomarker for Parkinson’s ( to read more about this).
  • researchers investigating T-cell replicative senescence report reduction in the CD8+ population in people with Parkinson’s versus healthy controls. Result “suggests that ‘abnormal’ immune ageing may contribute to the development of PD” ( to read more about this).

Clinical trial news

  • A randomised, double-blind clinical study finds that 4-week administration of DA-9701 (a new prokinetic drug) is safe & significantly improved gastric emptying rate in people with Parkinson’s, compared to gastroprokinetic agent, Domperidone ( to read more about this research).
  • Researchers propose an interesting adaptive approach to improving deep brain stimulation for Parkinson’s using motor cortex sensing ( to learn more about this research).
  • The results of a phase 2/3, randomised, double-blind, placebo-controlled, multi-center clinical trial assessing efficacy & safety of adjunctive rasagiline in Japanese Parkinson’s patients with wearing-off phenomena have been published ( to read more about this).
  • Cognitive training for freezing of gait (FoG) in Parkinson’s: a randomised controlled trial found that cognitive training can reduce the severity of FoG in the on-state, however larger sample replication is required ( to read more the research report and click here for the press release).
  • Pharmaceutical company Eli Lily has started recruiting for their Phase 2 PRESENCE clinical trial to test LY3154207 (an orally administered enhancer of dopamine receptor D1) for Parkinson’s Dementia ( to read more about this).
  • The BlueSky Project – a collaboration between industry giants pfizer and IBM – is ready to accept its first patient on a clinical trial at a house in upstate New York which is packed with sensors for monitoring PD ( to read a news article about this research).

The house built for Parkinson’s

  • Low doses of niacin in people with Parkinson’s may shift macrophage polarisation from M1 (pro-inflammatory) to M2 (counter-inflammatory) profile through the niacin receptor GPR109A ( to learn more about this and click here to read a SoPD post on the  topic).
  • Adamas Pharmaceuticals has published the pharmacokinetic data for GOCOVRI™ (amantadine) extended release capsules for Parkinson’s associated dyskinesias ( to read the report and click here for the press release).
  • The results of a randomised clinical trial evaluating the effects of Tai Chi in Parkinson’s has been published ( to read more about this).

Other news

  • eTherapeutics and C4X Discovery announce an agreement to collaborate on Parkinson’s. Using the 180 novel disease-associated genes that C4XD’s Taxonomy3 technology platform has uncovered to create new therapeutic approaches with C4XD’s Taxonomy3 technology ( for the press release).
  • MRI Interventions Inc & Voyager Therapeutics partner on Parkinson’s, to design next-generation navigation systems, software & cannula devices to provide further support & resources for Voyager’s gene therapy programs (Phase 2-3 trials for VY-AADC –  to read the press release).
  • Casma therapeutics is a biotech that has just launched with $59M for treatments targeting the cell’s garbage disposal system (Autophagy) in for inflammatory and neurodegenerative diseases, such as Parkinson’s ( to read the press release).

  • Interesting new study – called Rapsodi – for those who carry a GBA genetic variant/mutation (with and without Parkinson’s). Have a look: Click here to learn more.

  • Another interesting study: The Michael J. Fox Foundation and Verily Life Sciences have announced a new collaboration; involves giving the Verily Study Watch to 800 participants in the MJFF-led longitudinal Parkinson’s Progression Markers Initiative to better understand PD ( to learn more).

  • A very interesting viewpoint piece regarding clinical assessments for Parkinson’s, from an expert panel. Asking: – What should be measured? – Why is objective measurement better than current qualitative assessment? – When should objective testing occur? ( to read more about this).
  • FORMA Therapeutics and the University of Oxford announces a collaboration to identify, validate & develop deubiquitinating enzyme (DUB) inhibitors for the treatment of neurodegenerative conditions, like Parkinson’s. ( to read the press release and click here to read a SoPD post on this topic).
  • Researcher at Lund University in Sweden announced a new collaboration with Novo Nordisk as part of an effort to take large-scale stem cell therapy to the clinic for Parkinson’s (Click here to read more about this).

  • A smart perspective piece on precision medicine for Parkinson’s calling for: 1. making access to data & biosamples the norm, 2. partnering with patients & their families, 3. driving biomarker validation, and 4. rethinking our approach to drug development Amen! ( to read the piece).
  • Verge Genomics has announced that it is partnering with UC San Diego & VIB Life Sciences to sequence single cells from people with Parkinson’s. Using machine learning platform to analyse genomics data and lead to new PD treatments ( to read the press release).
  • Biotech firm Alkahest has received a grant from the Michael J. Fox Foundation to support preclinical evaluation of ALK4290 for Parkinson’s ( to read the press release).

Review articles/videos

  • A really good overview of dystonia in Parkinson’s on the Parkinson’s UK medium blog (Click here to read it)
  • Interesting review article on Leucine-Rich Repeat Kinase 2 (LRRK2) in Parkinson’s. Providing an update on the PD-associated biology as well as potential therapeutic developments ( to read this review).
  • A new review article summarises the research on the 7 main genetic mutations (α-synuclein, LRRK2, PINK1, Parkin, DJ-1, VPS35 and GBA1) linked to Parkinson’s, and explores mechanism of cell death ( to read this review).
  • Interesting review of the emerging potentially disease‐modifying strategies that target alpha synuclein for the treatment of Parkinson’s, discussing both direct & indirect approaches ( to read this review).
  • Interesting discussion about whether Parkinson’s may begin in the gut on the Scientific American website. Covers a lot of bases, including the Enterin clinical studies ( to read this article).

  • Interesting short review of the support cells in the brain (Astrocytes & Microglia) in the context of Parkinson’s. Mutations in PD-associated genes may alter the functions of these cells, possibly contributing to disease onset & progression ( to read the article).
  • Interesting section on Parkinson’s in this review of autophagy (waste disposal) in age-associated neurodegeneration. The conclusion: “upregulation of autophagy holds potential for the development of therapeutic interventions” ( to read the review).
  • Interesting historical & cross-cultural (Europe, China & India) perspectives on Parkinson’s ( to read the article).
  • Interesting (short) section on Parkinson’s in this review of old drugs being repurposed as new treatments for neurodegenerative conditions ( to read the review).
  • Interesting interview with Dr Mark Frasier, Senior Vice President of Research Programs at the Michael J. Fox Foundation regarding precision medicine in Parkinson’s – “One critical barrier is finding objective biological markers”. Other challenges: having “an engaged and mobilized patient group that participates as partners”; and “an enhanced level of data sharing and openness to this in the research community, both in academia and industry, would accelerate the pace of discovery and replication” Amen! ( to read this interview).

Dr Mark Frasier, Michael J. Fox Foundation

  • A very thorough review of neuroimaging applications research in Lewy body dementia (DLB). Early diagnosis of DLB has been challenging in the context of Parkinson’s dementia and Alzheimer’s. Current & new technique aid diagnosis ( to read the review).
  • An excellent & very thorough overview of gene therapy (symptomatic & disease modifying approaches) for Parkinson’s (Click here to read this review).
  • Interesting small section of Parkinson’s in the review exploring “Environmental Exposure from Neurodevelopment to Neurodegeneration” ( to read the review).

  • A nice & concise review of where things are with gene editing in neurodegenerative conditions like Parkinson’s – a useful update on CRISPR, zinc-finger nucleases & TALENS ( to read this review).
  • Interesting review on the bad boy of Parkinson’s: alpha synuclein. From early synaptic dysfunction to neurodegeneration – this covers it all ( to read the review)

  • An excellent & thorough systematic review of the research on polyphenols (natural organic chemicals) in Parkinson’s. Including preclinical studies, gut absorption, brain permeability,… VERY thorough! ( to read this review).
  • Van Andel Institute researchers provide an excellent & thorough review of how inhibition of mitochondrial pyruvate carriers represents a powerful target for providing neuroprotection in Parkinson’s (includes interesting discussion on experimental drug MSDC-0160 –  to read the review).

  * * * * * * * * * * * *

And there it is, just some of the highlights from May 2018 – another very busy month of Parkinson’s research. Hopefully there will be bits and pieces of interest for everyone in the list. Much of the material used here was collected from the Science of Parkinson’s Twitter feed (and there is a lot more posted there each day).

Any thoughts/feedback would be greatly appreciated (either in the comments below, or contact me directly).

And now: on to June!

EDITOR’S NOTE: The information provided by the SoPD website is for information and educational purposes only. Under no circumstances should it ever be considered medical or actionable advice. It is provided by research scientists, not medical practitioners. Any actions taken – based on what has been read on the website – are the sole responsibility of the reader. Any actions being contemplated by readers should firstly be discussed with a qualified healthcare professional who is aware of your medical history. While some of the information discussed in this post may cause concern, please speak with your medical physician before attempting any change in an existing treatment regime.

In addition, many of the companies mentioned in this post are publicly traded companies. That said, the material presented on this page should under no circumstances be considered financial advice. Any actions taken by the reader based on reading this material is the sole responsibility of the reader. None of the companies have requested that this material be produced, nor has the author had any contact with any of the companies or associated parties. This post has been produced for educational purposes only.

Published by Simon

I am the Director of Research at Cure Parkinson's. Before that I was working as a Parkinson's research scientist at the University of Cambridge where I conducted both clinical- and lab-based research on Parkinson's. I have worked in the Parkinson's research field for over 15 years - both academically and in biotech ventures. All of my views/opinions expressed here are solely my own, and may not reflect the views of my employer or associated parties.

4 thoughts on “Monthly Research Review – May 2018”

    1. Hi Kevin,
      The pace is utterly breath-taking at the moment. The real issue is how to make any of it applicable for the community. The pace of the research and the results only seems to be accelerating, while the application of it is being left in the dust. How can we speed up the usefulness of the data. I’m not sure how we bridge that expanding chasm.
      Kind regards,
      Simon

      Like

      Reply

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