Monthly Research Review – March 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 March 2018.

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

So, what happened during March 2018?

In world news:

March 25th – Qantas launches direct non-stop Boeing 787 Dreamliner flights between Perth Airport and Heathrow Airport, making it the first commercially non-stop service between Australia and the United Kingdom (17 hours on a plane – strewth!).

Boeing 787 Dreamliner. Source: Deredactie

March 14th – Prof Stephen Hawking, English theoretical physicist and cosmologist, sadly passed away at age 76. Diagnosed with in a very rare early-onset, slow-progressing form of Amyotrophic lateral sclerosis (ALS; also known as motor neurone disease or MND) in 1963 at age 21, he was gradually left him wheel chair bound. An amazing mind and a sad loss.

p03dn27d

Prof Stephen Hawking. Source: BBC

A funeral for Prof Hawking was held in Cambridge. The bell at Great St. Mary’s tolled 76 times at the start of the service. His remains will be cremated and his ashes will be interred at London’s Westminster Abbey near the remains of Isaac Newton.

King’s Parade in Cambridge was absolutely packed with mourners. Source: News.rthk

March 19th – In other sad news, ‘Sudan’, the world’s last male northern white rhinoceros died in Kenya, making the subspecies ‘functionally extinct’. Poachers had reduced the population from 2000 in the 1960s to just 15 1980s, and efforts to keep the species alive .

Sudan, the last surviving male northern white rhino. Source: PBS

March 24 – In over 800 cities internationally, people participated in student-led demonstrations against gun violence and mass shootings, calling for stronger gun control in the ‘March for our lives‘.

Source: Marchforourlives

And finally, on the 17th March, a driver in Milton Keynes (UK) got into big trouble with the law when he was pulled over and presented a police officer with an obvious fake drivers license (Source: Sky News):

Fake news Mr Trump? Clearly a fake. Everyone knows Homer lives at 742 Evergreen Terrace!

In the world of Parkinson’s research, a great deal of new research and news was reported:

In March 2018, there were 732 research articles added to the Pubmed website with the tag word “Parkinson’s” attached (2312 for all of 2018 so far). In addition, there was a wave to news reports regarding various other bits of Parkinson’s research activity (clinical trials, etc).

The top 5 pieces of PD news

1. Positive gene therapy clinical trial update: Biotech company Voyager Therapeutics have provided an update of their ongoing Phase 1b gene therapy clinical trial of VY-AADC. This Phase 1b, open-label trial includes 15 people with advanced Parkinson’s and disabling motor fluctuations, treated with a single administration of VY-AADC (a virus encoding an enzyme required for the production of dopamine from L-dopa). VY-AADC was well-tolerated in all 15 participants treated with no vector-related serious adverse events (primary endpoint: safety). No comments on secondary endpoints (PET imaging). “Cohort 2 at 18 months, patients had a mean increase of five hours a day of on-time without any dyskinesia and experienced 65% less off-time”. Phase 2-3 clinical trial program on track to begin dosing participants in mid-2018 ( to read the press release and click here to read a SoPD post on this topic).

2. Pα-syn*: a new species of alpha synuclein: Researchers at the Scripps Institute in Florida have identified a conformationally distinct species of the Parkinson’s-associated protein alpha synuclein. It is present in neuronal cultures & mice brains exposed to α-synuclein fibrils AND in the postmortem brains of people who passed away with Parkinson’s. The results of the research suggest that alpha-synuclein undergo autophagic degradation (waste recycling), but this process is incomplete. This leads to the formation of a form of alpha synuclein that the researchers called pα-syn*. These Pα-syn* aggregates exit the lysosomes and then localise to mitochondria where they start to cause trouble. The researchers conclude that “pα-syn* is a major neurotoxic species inducing mitochondrial damage, fission, & mitophagy, therefore constituting a central player in PD pathogenesis”( to read the abstract of this research and click here to read a SoPD post on the topic).

3. Parkinson’s associations: Genome company 23andMe has posted a new preprint manuscript (on the website BioRxiv) in which they looked at associations between Parkinson’s & 840 phenotypes (observable characteristics). Analysis involved 5,141 cases of PD and 65,459 age- and sex-matched controls. PD diagnosis was associated with 149 independent phenotypes. Their results suggest migraine, obsessive-compulsive disorder, seasonal allergies, and anemia were associated with Parkinson’s, but not disease duration. Some very interesting new associations in this research report ( to read the manuscript and click here to read an SoPD post on this topic).

4. Three conditions, one common theme: Three different neurodegenerative conditions (Alzheimer’s, Parkinson’s, and Huntington’s) which are characterised by protein clustering – or aggregation – apparently share a common feature. The aggregated form of their protein (in a configuration that is called oligomers) each form a shape which reacts with the proteasome inside of cells. The proteasome are structures inside cells that function as garbage disposal units, breaking down waste and old proteins, allowing their components to be reused or disposed of. This shared structure between the three conditions, has been found to impair normal proteosome function, with low nanomolar affinity. This could explain certain aspects of all of these neurodegenerative conditions ( to read more about this research).

Source:

5. Inhaled anaesthetics: Inhaled anaesthetics have long been known to have biological effects beyond simply sedating individuals. Some of those effects are beneficial, while others….mmm, well, not so beneficial. New research from Toronto suggests that inhaled anaesthetics may induce neuronal protein aggregation and also affect endoplasmic reticulum trafficking. The endoplasmic reticulum is a structure closely aligned with the nucleus in a cell, and it is critically involved with protein synthesis. The researchers do not look at Parkinson’s-associated proteins (such as alpha synuclein or Tau) directly, but there are interesting potential implications ( to read the research report).

Source: Medicalxpress

Basic biology news

  • Loss of the sense of smell may be one of the first signs of Parkinson’s. Researchers have found that inhibition of oxidative stress in cholinergic projection neurons fully rescues ageing-associated olfactory circuit degeneration in flies ( to read the research report).

Source: ELife

  • Basal levels of mitophagy (controlled disposal of mitochondria inside cells) is minimally affected by the loss of Parkinson’s-associated genes PINK1 or PARKIN in flies. Perhaps a rethink is required on their role in PD? ( read more about this).
  • Phosphatidylglycerol micellar tubules are involved in stimulating the formation of the toxic form of Parkinson’s-associated alpha synuclein (amyloid fibrils –  to learn more).
  • Parkinson’s-associated gene ATP13A2 gene evolved early in animal evolution. Loss-of-function mutations in ATP13A2 (PARK9) are associated with a severe juvenile-onset autosomal recessive form of PD ( to read more).
  • New research systematically comparing lysosomal function (breaking down old proteins) in different neuronal populations in Parkinson’s, Multiple systems atrophy (MSA), and non-diseased brains indicates variations between disease groups and cell populations ( to read the abstract of this research).
  • Interesting manuscript on BioRxiv: they get really up close and personal with Parkinson’s-associated alpha synuclein fibrils (cryo-electron microscopy at 3.4Å resolution).Their “findings on the mechanism of fibril elongation and protofilament interaction open the door to the informed design of molecules for diagnostics or treatment” ( to read the manuscript).

Source: 

  • 2018 is the 20th anniversary of the discovery that genetic mutations in the PARKIN (PARK2) gene are associated with Parkinson’s. Lots of PARKIN research. Today: further evidence that PARK2 is a tumor suppressor gene that negatively affects angiogenesis ( to read the research report).
  • A rare early-onset form of Parkinson’s is due to mutations in the Synaptojanin 1 (Synj1) gene (aka PARK20). Researchers report that Synj1 plays a crucial role in regulating the homeostasis & functions of early endosomal compartments in different cell types ( to learn more about this).
  • Mitochondria supply cells with power. New research suggests that loss of Parkinson’s-associated PARKIN impairs mitochondrial function and leads to muscle atrophy. Yet another reason for exercise ( to read more about this).
  • Nicotinamide improves various aspects of ‘healthspan’ (the period of healthy life), but not lifespan, in mice. It reduces oxidative stress & inflammation ( to read the abstract of this research).

Nicotinamide. Source: Wikipedia

  • Nurr1 is a protein that is viewed as a potential target for future Parkinson’s therapies. A new biorxiv preprint manuscript reports on the nature of the ligand-binding pocket in the Nurr1 ligand-binding domain – very dynamic interactions! (
  • Ubiquitin C-terminal hydrolase L1 (UCHL1) is believed to be involved in Parkinson’s. Vietnamese and Japanese researchers now have a fly model in which UCHL1 is removed in just the dopamine neurons. Useful model of PD for screening future therapeutics ( to read more about this).
  • Researchers have found gut microbiome-metabolome signatures in mice genetically prone to develop dementia, fed a normal or fatty diet. An effect of transgenic background on gut microbiome-metabolome? Enhanced by high-fat diet? Implications for Parkinson’s? ( to learn more about this).

The gut and brain connection. Source: Everydayhealth

  • New data suggests that peripheral immune signalling plays an important role in the regulation of neurodegeneration in mouse model of LRRK2-associated Parkinson’s – new targets for interfering with the onset & progression? ( to read more about this research).
  • High levels of extracellular Parkinson’s-associated alpha synuclein results in a reduction of the firing rate of the neuronal networks by disrupting synaptic transmission, which later possibly contributes to neuronal cell loss ( to learn more about this research).
  • Researchers from Spain have published a concept article aimed at demonstrating the rationale of targeting extracellular alpha synuclein from cerebrospinal fluid as a new treatment strategy for Parkinson’s ( to read more about this).
  • The pathogen Pseudomonas aeruginosa produces & secretes a glycolipid called rhamnolipid. Danish researchers report that rhamnolipid interacts with Parkinson’s-associated alpha synuclein – implicating microbe metabolites in origin & propagation of PD ( to read more about this).

Pseudomonas aeruginosa. Source: Aerzteblatt

  • New study from Swedish researchers provides an in vivo genome-wide analysis of permissive/repressive histone modifications coupled to gene expression in these rare neuronal subtypes – including those affected in Parkinson’s ( read that research report).
  • Enrichment of senescent cells (non-dividing cells) in tissues with age has been associated with Parkinson’s. New research from Australia suggests that elevated copper in senescent cells is associated with impairment of autophagic-lysosomal function ( to read more about this research).
  • The ordered assembly of amyloid proteins is a common feature of neurodegenerative diseases, like Parkinson’s. Researchers used single-molecule microscopy to study the assembly & replication of tau at the single aggregate level ( to read more about this).
  • Deep brain stimulation (DBS) aiding our understanding of the brain. Researchers demonstrate & define a causally important time window of subthalamic nucleus involvement in the process of decision making in people with Parkinson’s & DBS ( to read the abstract of this research).
  • Trehalose, an osmolyte, has previously been shown to inhibit Parkinson’s-associated α-Synuclein aggregation. New research suggests that trehalose modulates the transitions of α-synuclein; speeds up onset of aggregation, but reduces fibril load ( to read the abstract of this research).

Source: 

Disease mechanism

  • Removal of of a gene called ARL6ip5 (ADP-ribosylation-like factor 6 interacting protein 5; also known as JWA) from astrocytes (the supportive helper cells in the brain) exacerbates dopamine neuron degeneration in models of Parkinson’s, by decreasing glutamate transporters ( to read more about this).
  • Disruption of Parkinson’s-associated LRRK2 in Zebrafish leads to hyperactivity at adult stage, and a weakened antibacterial response ( to read more about this).
  • Parkinson’s is accompanied by dysregulation in blood clotting. Researchers have found that lipopolysaccharide-binding protein can prevent this. Is this further evidence implicating inflammatory microbial cell wall products accompanying this condition? ( to read the research report).

Source: Plosone

  • Reduces levels of inflammation kinase EIF2AK2 (aka PKR) results in less Parkinson’s-associated alpha synuclein toxicity, supporting the idea that neuroinflammatory processes may play a role in modulating the condition ( to read more about this).
  • Fixed speed treadmill training for 30 minutes per day reduces motor deficits & improves dopamine functions in a rat model of Parkinson’s (Exercise began in the 1st week after the 6-OHDA lesion –  to learn more).
  • Emory University researchers have published data on a selective phosphodiesterase 10A inhibitor called MR1916 (from Mochida Pharmaceuticals) that reduces Levodopa-induced dyskinesias in a primate model of Parkinson’s ( to read the abstract of this research). Mochida Pharmaceuticals are conducting a safety & tolerability clinical trial of MR1916 in the UK at the moment – could be interesting to watch (Click here to learn more about that trial).
  • Anacardic acids from cashew nuts prevent behavioural changes and oxidative stress induced by the neurotoxin rotenone in a rodent model of Parkinson’s. These neuroprotective properties of anacardic acids require further investigation ( to read the abstract of this report).

Cashew nuts. Source: Fitday

  • Dart Neuroscience LLC researcher identify endothelin-converting enzyme-1 (Ece1) as a disease-modifying gene in fly models of Parkinson’s. ECE1 also suppresses alpha synuclein A30P-induced motor deficit & dopamine neuron loss in mice ( to read more about this).
  • Researchers report a new method that allows the detection of amyloid fibers in Parkinson’s. Detection of amyloid fibrils down to nanomolar concentrations ( to read the abstract of this research).
  • 50% of people with autosomal recessive juvenile Parkinsonisms have a mutation in their PARKIN gene. PARKIN regulates the recycling & disposal of mitochondria. New research highlights the impact of altered phosphorylation on loss of function of PARKIN ( to read more about this).
  • A useful resource for understanding the molecular pathways linking pathologic mechanisms in both Parkinson’s and Alzheimer’s: 127 321 unique peptides identified from over 1.5 million peptide spectral matches, which mapped to 11 840 unique proteins groups! ( to read the research report).
  • Endoplasmic reticulum (ER) stress is associated with Parkinson’s. New research suggests ER stress also induces dynamic remodelling of mitochondrial morphology in a PERK-regulated process. Without PERK signalling, mitochondria go haywire ( to read this research article and click here for the press release).
  • Kir6.1/K-ATP channel is essential for maintaining M2 microglia. Kir6.1 deficiency switches microglia from the beneficial M2 phenotype into the nasty M1 phenotype, which accelerates dopamine neuron loss in mouse models of Parkinson’s. New target 4 therapy? ( to learn more about this).
  • Astaxanthin, a keto-carotenoid, has been found to be neuroprotective in a mouse model of Parkinson’s. More effective in young mice than old, “suggests that ageing is a critical factor to consider during the development of novel therapeutics” ( to learn more about this research).

Astaxanthin. Source: Clearsynth

  • Atomic force microscopy reveals formation of nanopores & roughness in the cell surface (leading to membrane disruption) caused by Parkinson’s-associated alpha synuclein (oligomers); leads to elevated levels of nitric oxide & S-nitrosylation of key proteins ( to read more about this).
  • Frontotemporal dementia with Parkinsonisms linked to chromosome 17 (FTDP-17) is a neurodegenerative disease caused by genetic mutations in MAPT, the gene encoding for tau. An RNA-targeting CRISPR-Cas family has been used to alleviate tau levels in human cells ( to read the research report).
  • Vitexin, a flavonoid compound isolated from Chinese hawberry, has been shown to be neuroprotective in cell and mouse-based models of Parkinson’s ( to read more about this).
  • Greek researchers provided evidence that a decrease in Glucocerebrosidase (GCase) enzymatic activity or high levels of mutant GCase can affect the secretion of alpha synuclein. Important implications for GBA-associated Parkinson’s? ( to read more about this).
  • Danish biotech Orphazyme AS has a new manuscript on BioRxiv suggesting that CNS-penetrant drug Arimoclomol enhances the activity of mutated GCase across several genotypes from Gaucher patients. Implications for GBA-associated Parkinson’s? ( to read that manuscript and click here to read a SoPD post on this topic).

  • TRIM28 has been found to regulate toxicity of alpha synuclein & tau in models of Parkinson’s. New BioRxiv manuscript demonstrates that inhibition of TRIM28 during adulthood is not associated with negative consequences ( to learn more about this).
  • UNC-51-like kinase 1 (ULK1) is an initiating enzyme in autophagy (the waste disposal process in cells). Researchers have found a small molecule 33i (BL-918) that is a potent activator of ULK1. 33i protected dopamine cells in a mouse model of Parkinson’s ( to read more about this).
  • Another article on Unc-51 like kinase 1 (ULK1) reported altered phosphorylation of this autophagy initiating enzyme (at Ser758) following prolonged inhibition of Parkinson’s-associated protein LRRK2 ( to read more about this).
  • Taurine, a major constituent of bile, protected dopamine neurons in a mouse model of Parkinson’s via inhibition of microglial M1 state. Taurine also attenuated the aggregation of alpha synuclein ( to learn more about this).

Taurine. Source: Wiktionary

  • Aquaglyceroporin AQP9 is a protein present on the dopamine neurons (plasma membrane & inner mitochondrial membrane). New research reports that deletion of AQP9 in dopamine neurons is protective in a mouse model of Parkinson’s. New therapeutic target? ( to read the research report).
  • New postmortem research suggests that in Parkinson’s, mitochondria – the power stations of the cells – are increased within axons & the mitochondria produce higher levels of key electron transport chain proteins compared to controls. “Neurons may attempt to maintain mitochondrial populations within remaining axons and synapses in PD disease to facilitate continued neural transmission in the presence of neurodegeneration, potentially increasing oxidative damage”( to read the research report).
  • Parkinson’s associated alpha‐synuclein protein aggregates activate calcium pump SERCA leading to calcium dysregulation. SERCA inhibition protects cells from α‐synuclein aggregate stress ( to read this research report).

Source: 

  • A new molecular contributor to glial maintenance of dopamine neurons: Glutamate stimulation of dopamine neurons in early development, without the protective actions of SWIP-10, contributes to insults that drive neuron degeneration. Implications for Parkinsons? ( to read the full report).
  • Researchers find Lewy body-like pathologies, dopamine cell loss & stabilisation of Parkinson’s features in aged monkey model of PD (MPTP –  to learn more about this).
  • Researchers report data that boosting SOD (Superoxide dismutase) levels rescues PINK1 & Parkin genetic models of Parkinson’s – also highlights the potential utility of SOD-mimetic compound, M40403 ( to read the research report).

Clinical research

  • Evidence from 58 people with Parkinson’s and 59 non-neurological disease controls suggests that salivary heme oxygenase-1 concentrations may provide a useful, noninvasive, & relatively inexpensive biomarker of early idiopathic PD ( to read more about this).
  • Researchers found Parkinson’s-associated Glucocerebrosidase (GBA) gene variants in 12% of patients with idiopathic REM sleep behaviour disorder ( to read the abstract of this research).
  • Using the National Health Insurance Research Database of Taiwan, researchers have revealed that the risk of an overactive bladder is higher in people with idiopathic Parkinson’s than age matched controls ( to read the research article).
  • Further evidence has been published for a distinctive atypical form of Parkinson’s in the Caribbean: A new cluster in the French West Indian Island of Martinique ( to read the abstract on this research).

French West Indian Island of Martinique

  • Researchers in South Korea propose an automated tremor score estimation algorithm for people with Parkinson’s, based on convolutional neural network, using a wearable device ( to read the research abstract).
  • Brain imaging study from Imperial College suggests that people with tremor-dominant Parkinson’s have relatively mild dopamine denervation compared to non-tremor individuals. Part of the PPMI study MichaelJFoxOrg ( to read more).
  • Brain imaging from 21 people with REM sleep behaviour disorder (& 29 controls) suggests extrastriatal monoaminergic dysfunction & enhanced microglial activation (particularly in the occipital lobe). Implications for Parkinson’s? ( to read more about this).

REM sleep behaviour disorder. Source: Nationalgeographic

  • Researchers from Chiang Mai University (Thailand) have provided an interesting report on the prevalence & clinical characteristics of probable REM sleep behaviour disorder (pRBD) in a Thai Parkinson’s population. Prevalence of pRBD was 48.5% ( to read more about this research).
  • No differences in motor/cognitive performance between individuals with rs356219 alpha synuclein-linked earlier onset Parkinson’s (compared to non-carriers with earlier onset PD), except reduced functional activity in posterior putamen & primary motor cortex ( to read more about this).
  • Korean research provide further evidence that weight loss in Parkinson’s is detrimental. Associated with rapid striatal dopaminergic degeneration (based on DATScan), and “associated with impairment in energy homeostasis” ( to read more about this research).
  • Low levels of Vitamin B12 in blood are common in Parkinson’s & are associated with neuropathy and cognitive impairment. New study from DATATOP Investigators indicates that low vitamin B12 status is common in early PD. Could early correction be beneficial? ( to learn more).

Vitamin B12. Source: Zliving

  • Data from 13,507 caregivers from 12 European countries looking at what matters in public policy & the health of caregivers (includes Parkinson’s carers). Better care associated with: 1. more free time, 2. dealing with emotions, 3. more skills development ( to read about this research).
  • Levels of Parkinson’s-associated alpha synuclein connected to Alzheimer’s-associated β-Amyloid are increased in red blood cells of people with Parkinson’s, and also correlates with severity of the condition ( to read this research report).
  • New study suggests that compared to control subjects, people with Parkinson’s have a significantly thinner retinal nerve fiber layer in the temporal retinal quadrant of the eye. Novel diagnostic aid? ( to read the abstract of this report).

Retinal nerve fiber layer. Source: Osapublishing

  • New study demonstrates that acute emotional stressors can exacerbate motor deficits in Parkinson’s ( to read the abstract of this report).
  • A retrospective study of 390 people with Parkinson’s who did not have freezing of gait (FOG) at baseline, finds that presynaptic striatal dopaminergic denervation predicts the later development of FOG in these subjects ( to read more about this).
  • New manuscript on BioRxiv describing data from 388 drug naïve people with Parkinson’s that suggests associations between peripheral inflammation & DATSCAN brain imaging data of the striatal nuclei in different motor subtypes of Parkinson’s ( to read that manuscript).
  • Genetic variations in the GBA gene (which produces the enzyme glucocerebrosidase) are among the most common genetic risk factors for Parkinson’s An interesting meta analysis of Parkinson’s genetic risk factors in 20,267 people with PD and 24,807 controls highlights differences in GBA variants between different nations/ethnic groups around the world ( to read the research report).
  • Progressive supranuclear palsy (PSP) is a rare movement disorder, often difficult to distinguish from Parkinson’s. New research suggests metabolic brain network activity may serve as a reliable & objective marker of PSP ( to read the abstract about this research).
  • New brain imaging method combines three drug templates (one built-in SPECT template in SPM software & two self-generated MRI-based and HMPAO-based TRODAT-1 templates) for the semiquantitative analysis of dopamine activity in Parkinson’s ( to read the research report).
  • Six-month outcome data available for 133 people with Parkinson’s who underwent deep brain stimulation surgery suggests very similar results in motor, quality of life and medication when comparing asleep & awake surgical procedures ( to read more about this).

DBS. Source: Bristolhealthpartners

  • The Executive Summary of the Congress of Neurological Surgeons systematic review & evidence-based guidelines on Subthalamic Nucleus & Globus Pallidus focused Deep Brain Stimulation for Parkinson’s has been published ( to read more about this).
  • New research indicates that the site of stimulation influences the emergence of neuropsychiatric symptoms after subthalamic deep brain stimulation for Parkinson’s ( to read more about this).
  • Thalamocortical dysrhythmia (TCD) is a model proposed to explain divergent neurological disorders. New study suggests that a machine learning approach to TCD can identify brain areas that are common to the Parkinson’s, pain, tinnitus, & depression ( to read the research report).
  • New Tau (18F-AV-1451) brain imaging study indicates increased levels of Tau in the parietal lobe associated with executive impairment (Dementia w/ Lewy Bodies), & decreased levels in the substantia nigra associated with parkinsonisms (Parkinson’s). ( to learn more about this).

Source:

  • Functional neurological disorder is a condition in which people experience neurological symptoms such as weakness, sensory symptoms & blackouts. New research suggests functional manifestations may be prodromal to Parkinson’s in 1/3 of cases ( to read more about this).
  • New research from Taiwan suggests that people with asthma–chronic obstructive pulmonary disease syndrome (ACOS) have increased risk of Parkinsons. Using inhalers (corticosteroids ≧0.13 gram) reduced risk, except w/ high dose corticosteroids (>0.43 gram) ( to read the research report).
  • Italian researchers have published a report demonstrating that ‘placebo’ was effective in reducing resting tremor in half of people with tremor-dominant Parkinson’s ( to learn more about this research).
  • Swedish & Aussie researchers have published an interesting report on changes to the striatal nuclei in Parkinson’s. Atrophy of the caudate nucleus correlates w/ poorer perceptual & cognition, while the putamen shrinkage correlates w/ poorer motor symptoms ( to read more about this).
  • Italian researchers used real-time gait phase recognition (from inertial sensors placed on feet) to measure gait quality in 26 people with Parkinson’s, both in OFF & ON levodopa conditions, & in 11 healthy subjects ( to read more about this).
  • During walking, people with Parkinson’s make more task-irrelevant fixations compared to controls. “Improving the saliency of relevant stimuli may be a useful, cost-effective home-based modification for PD” ( to explore more on this topic).
  • Researchers have made a wearable device that monitors stomach activity over 24 hours – could be useful for assessing gastric emptying patterns & circadian-related oscillations in Parkinson’s ( to read more about this).

Monitoring gut activity. Source: 

  • Researchers provided further evidence of dopamine abnormalities following a moderate–severe traumatic brain injury – implications for Parkinson’s? ( to read the research article on this topic).
  • Does Pisa syndrome affect upper limb function in peope with Parkinson’s? An observational cross-sectional study from Italy suggests that the answer is YES ( to learn more about this).
  • New results indicate that 8 weeks of body weight-supported treadmill training resulted in increased ranges of motion for the pelvis, hips, knees and feet for people with Parkinson’s who have undergone deep brain stimulation ( to read the abstract regarding this research).
  • Othello syndrome is a type of paranoid delusional jealousy, characterised by the false absolute certainty of the infidelity of a partner. A review of 67 cases of Parkinson’s with Othello Syndrome has just been published. Dopamine agonists could be involved ( to learn more about this).
  • New historical Israeli cohort study of data from 1.2 million adult members of a large health organisation (btwn 2000 & 2015) finds positive relationship between Parkinson’s & risk of basal cell carcinoma. No association btwn PD & melanoma ( to read the abstract about this research).
  • A Biorxiv preprint manuscript on the Oxford Nanopore MinION – the only portable real-time device for DNA and RNA sequencing. It can pick up all of the tricky genetic variants in Parkinson’s-associated GBA gene. New diagnostic cools for PD? ( to read the manuscript).

DNA sequencing in your palm. Source: Nanoporetech

  • Interesting case study of a person with Parkinson’s who had a magnetic resonance imaging–guided focused ultrasound thalamotomy REOPERATION after benefits from first procedure declined. “In case of tremor recurrence, DBS has the advantage of adjustability” ( to read more about this).
  • An interesting report of a 21 year retrospective study of 332 patients with Parkinon’s (69.9% men, mean age 58 years) who underwent deep brain stimulation ( to read more about this research).
  • Quantitative analysis of bradykinesia & rigidity in Parkinson’s. Researchers identified the most sensible place to locate sensors for monitoring PD bradykinesia & rigidity, and identified objective indexes able to discriminate PD OFF/ON motor status ( to learn more about this).
  • German researchers look at how age & sex may impact the diagnostic accuracy of prodromal Parkinson’s ( to learn more).
  • Rhythmic and musical skills, which can be modulated by musical training, may increase beneficial effects of rhythmic auditory cueing in Parkinson’s ( to read more about this).
  • Interesting look at how device‐aided therapy can help to sustain or increase daily activities & workforce participation in people with Parkinson’s who have not yet reached retirement age ( to read more about this).

  • The Parkinson’s Progression Marker Initiative presents 5‐year longitudinal data on the change of the MDS‐UPDRS & other clinical measures as well as dopamine transporter imaging outcomes in early PD. “These results provide a framework for designing studies that incorporate clinical and DAT imaging measures in de novo Parkinson’s participants. Such studies may signal a more accurate and efficient process toward the development of disease‐modifying treatments for PD” ( to read more about this).
  • In another Parkinson’s Progression Markers Initiative-related study, four distinct motor progression groups for Parkinson’s have been identified (and adjusted for baseline motor differences) from data collected in the PPMI study ( to read more about this).
  • Another example of whole-body quantification of bradykinesia in Parkinson’s participants using multiple inertial sensors – Successfully identified the differences within the PD group, assessing ON and OFF meds ( to find out more about this research).
  • New brain imaging research suggests that excessive daytime sleepiness in Parkinson’s may be associated with caudate denervation ( to read the abstract of this report).
  • New Biorxiv preprint manuscript suggests that a tendency towards being a “Morning person” – a state driven by the circadian clock – increases risk of developing Parkinson’s ( to read the manuscript).
  • Carriers of the Parkinson’s-associated LRRK2 p.N551K-p.R1398H-p.K1423K genetic variant have a reduced risk for developing rapid eye movement (REM)-sleep behaviour disorder ( to read more about this research).
  • “HopkinsPD” sounds like a police drama, but it is actually a useful app available through the Parkinson Voice Initiative. Interesting report on using HopkinsPD, smartphones & machine learning to quantify Parkinson’s. Mobile PD Scoring ( to read this report).
  • Using natural typing interaction with keyboards to detect motor impairments in early Parkinson’s. New study validate the neuroQWERTY algorithm in an uncontrolled at-home setting. An objective, user-convenient, & quasi-continuous monitoring tool for PD ( to read the abstract of this report).
  • Parkinson’s-associated protein alpha synuclein is present in dental calculus (a form of hardened dental plaque), but the total concentration is not a suitable biomarker for sporadic PD ( to learn more about this research).
  • Supervised versus unsupervised technology-based levodopa monitoring in Parkinson’s: an intra subject comparison. Promising open pilot study result for future telemedicine applications ( to find out more about this study).

Clinical trial news

  • Results from a safety & efficacy clinical study of levodopa-carbidopa intestinal gel: results from an open-label extension study in Japanese, Korean & Taiwanese patients with advanced Parkinson’s ( to read more about this).
  • GPR109A is an anti-inflammatory receptor that Niacin has a high affinity for. A new clinical trial of Niacin in Parkinson’s will be exploring this anti-inflammation role in Parkinson’s disease (Click here to learn more about this trial and click here to read more about this drug).

  • Pharmaceutical company Lundbeck announced that it was acquiring Prexton therapeutics. Through this purchase, Lundbeck will own the rights to Foliglurax, a positive allosteric modulator of mGluR4 which is under clinical development for Levodopa induced dyskinesias in Parkinson’s. Foliglurax entered phase II clinical testing for in July 2017, and we should know the results of that trial by the end of this year or early 2019 (Click here to read the press release regarding the purchase).
  • A randomised, double-blinded study of multi-target non-invasive brain stimulation – via transcranial direct current stimulation – suggests improvements in freezing of gait in Parkinson’s ( to learn more about this).

  • Synthetic squalamine (a compound from the spiny dogfish which reduces the toxicity of alpha synuclein) is being clinically tested for Parkinson’s. Today the biotech company Enterin Inc. announced completion of recruitment for their phase II trial ( to read the press release).
  • International Stem Cell Corporation has announced that it has completed the dosing of their second cohort in their cell transplantation clinical trial for Parkinson’s ( to read the press release).

Other news

  • Western University researchers have produced a prototype glove that reduces tremors in people with Parkinson’s ( to read the press release).
  • One year in and so much accomplished: Loads of interesting research being funded, plus a nice new website: the Parkinson’s community should check out the Silverstein Foundation (and Arvinas Science! Very interesting company!). They also announced that their startup ‘Prevail Therapeutics’ raises $75M for Gene Therapy programs for Parkinson’s – way to celebrate your birthday Silverstein foundation! ( to read the press release and Click here to read a SoPD post on this Parkinson’s organisation).

Source: Silverstein foundation

  • Repositioning of existing drugs could play a major role in the development of treatments for conditions like Parkinson’s. Researchers have made a computer-aided drug repositioning database (called eMatchSite) that compares drug-binding sites ( to learn more about this).
  • Parkinson’s UK increase their virtual biotech programme by funding a 12 month £1.2million project with Selcia Ltd to create molecules that increase activity of a selection of dopamine synthesis-related genes for Parkinson’s ( to read the press release).

  • The Parkinson’s Institute and Clinical Center and Denali Therapeutics have announced a partnership to explore new clinical endpoints for studies in people with Parkinson’s. Greatly needed! ( to read the press release).
  • Acorda Therapeutics has unveiled the “Live Well. Do Tell.” initiative to encourage conversations about Parkinson’s among the circle of care, including people with PD, care partners, advocacy & healthcare professionals (to learn more about this).

Source: LiveWellDoTell

  • A survey of 1775 individual from 11 European countries was published by published by the European Parkinson’s Disease Association. It evaluated each person’s experience during the moment of diagnosis. Conclusions: Improvements need to be made ( to read the full report).
  • The International Parkinson and movement disorder society evidence‐based medicine review has published an openaccess update on treatments for the motor symptoms (including dyskinesias) of Parkinson’s ( to read this report).
  • Congratulations to Parkinson’s UK and the Cure Parkinson’s Trust for winning the inaugural BenevolentAI Award. A collaboration between the two charities will leverage the BenevolentAI artificial intelligence platform to reason, deduce & suggest entirely new treatments for Parkinson’s ( to read the press release).

  • A new review provides you with basically everything you ever need to know about medical and surgical management of advanced Parkinson’s ( to read this OPEN ACCESS review).
  • And finally, have you ever gone looking for an overview of Parkinson’s therapies in development? Kevin McFarthing and PRAG have put together an INCREDIBLE webpage laying it all out. This is the most comprehensive list I have ever seen. A great example of someone in the Parkinson’s community, doing the hard work and showing us the lay of the land ( to see the page – and another good resource for clinical trials is the PDtrialtracker website).

And there it is, just some of the highlights from March 2018 – a 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 April!

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.

9 thoughts on “Monthly Research Review – March 2018”

  1. Kia Ora from NZ Simon! Thank you for all your hard work. I really look forward to your posts. The report on anaesthetic gases has me in a bit of a panic. Booked this month for a 7 hour surgery that must be done (unrelated to PD) Age 51, diagnosed last year, not yet on meds. Any other research you know of that might be relevant? Any detox programmes post surgery that can help? Don’t want this unruly house guest get anymore traction. Thanks. Regards Sara

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    1. G’day Sara,
      Hope you are enjoying the Indian summer weather down there – the bloody cold winter here has persisted too long. Glad you like the website. I am currently putting together a post on that anaesthetic research – it should be up in a day or so. The recent aggregation research does not involve Parkinson’s associated proteins, but there are other aspects of anaesthetics that are good for the Parkinson’s community to be aware of. Best to speak with your doctor if you have concerns about this issue, as they are more familiar with your medical history. I will see what we can do the whole detox matter, but I would suggest that you should not get yourself too worried about it – tens of thousands of inhaled anaesthetic procedures are conducted every day without incident. The worry about the surgery probably effects one more than the anaesthetic itself.
      Kind regards,
      Simon

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  2. Hi Simon, You’ve nailed it! For me anyway. Perfect headings and sub headings, level of detail and images for the monthly summary. Thanks again for the definitive PD resource. Martin

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    1. Hi Martin,
      Thanks for the kind words – glad you like the format. I am hoping to improve on it still, making it less of a shopping list and hopefully more reader. Any thoughts/ideas would be greatly appreciated.
      Kind regards,
      Simon

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  3. Simon,
    Thank you for the comprehensive review! A few years ago phenylbutyrate appeared to be a promising drug candidate for PD research. Do you know if there is any one researching it today? Cheers, David

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    1. Hi David,
      Glad you liked the post.
      For readers unfamiliar with this drug, Phenylbutyrate – an FDA approved histone deactetylase inhibitor – is used to treat rare metabolic disorders that prevent children from synthesizing urea. Back in 2010-ish, Curt Freed and colleagues at the University of Colorado found that phenylbutyrate almost tripled levels of a protein called DJ-1 (I explain what Parkinson’s-associated DJ-1 is in this post: https://scienceofparkinsons.com/2017/08/26/hey-dj-i-so-sit-rate/). Freed and others found that the drug protected dopamine neurons and rescued motor function in models of Parkinson’s (https://www.ncbi.nlm.nih.gov/pubmed/21372141 & https://www.ncbi.nlm.nih.gov/pubmed/22723850). Freed also suggested that Phenylbutyrate appeared to boost clearance of alpha synuclein from the brain, since brain concentrations of alpha synuclein fell in the phenylbutyrate treated mice while their blood levels of the protein nearly doubled. Based on all of this data, a a Michael J Fox funded phase I clinical trial was set up at Colorado University (three-week study of the drug in 20 people with Parkinson’s and 20 controls – https://clinicaltrials.gov/ct2/show/NCT02046434). Participants took 20 g per day, in the form of one teaspoonful of a liquid formulation with each meal. Although no results of the study have ever been published (as far as I’m aware – happy to be corrected on this), the ‘Final outcome’ comment on the Michael J Fox foundation webpage about the study (https://www.michaeljfox.org/foundation/grant-detail.php?grant_id=1186) suggests that no safety issues cropped up (the study did not assess efficacy). The scientists were planning a Phase II trial to start in 2016, but I am unaware of any such study.
      It should be noted, however, that phenylbutyrate has also been investigated for other neurodegenerative condition. It was reported safe in a 2009 Phase II trial of ALS/motor neuron disease (https://www.ncbi.nlm.nih.gov/pubmed/18688762) and in a Phase 2 Huntington’s trial (https://clinicaltrials.gov/ct2/show/NCT00212316 – no results publshed from that trial to my knowledge). So there was certainly interest in this compound, but I am not really aware of anyone currently working on phenylbutyrate in the area of Parkinson’s. May be of interest for someone to follow it up.
      I hope this helps.
      Kind regards,
      Simon

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      1. Simon – Thank you for such a detailed reply. I contacted one of the original researchers with the Fox-funded study – Dr. Wenbo Zhao. This is his reply: “Thanks for your email. We are actively seeking funding to perform the long term clinical trial of phenylbutyrate. Once we have the funding, we will announce it and you are welcome to participate the trial.”

        Sincerely,
        Wenbo Zhou, PhD
        Research Associate Professor
        University of Colorado School of Medicine

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  4. “Low levels of Vitamin B12 in blood are common in Parkinson’s ,,,Could early correction be beneficial?” Any informed opinion you can offer?

    “After preliminary testing, patients were offered the option of taking a daily multivitamin. Close to 50 percent of participants were found to have higher B12 on subsequent testing, suggesting that many took the supplement or improved their diets. For those patients who remained in a lower B12 level – suggesting they may not have started supplements – their annualized average increase of disability was 14.4 on the Unified Parkinson’s Disease Rating Scale (UPDRS), a test that assesses activities of daily life, motor skills, behavior and mood. In contrast, for the group whose B12 levels began low but improved during the study, their average increase in the UPDRS score was 10, showing less disability.”

    ‘“Our results suggest that the measurement of B12 levels early in Parkinson’s may be beneficial,” said Christine. “If levels are at the low end of normal, supplementation to get the level into the middle or upper end of the normal range may slow development of symptoms. But because we don’t know the impact of B12 on Parkinson’s disease, future studies are needed to determine if supplementing will change the disease trajectory.”’

    https://www.ucsf.edu/news/2018/03/409991/low-levels-vitamin-b12-may-worsen-walking-cognition-parkinsons-patients

    Thanks – the post seemed very well formatted, focused yet comprehensive

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    1. Hi Dkdc,
      Very interesting. Thanks for sharing. I will be doing a post on Vitamin B very shortly (famous last words). Glad you like the format.
      Kind regards,
      Simon

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