Monthly Research Review – June 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 June 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). 

So, what happened during June 2018?

In world news:

June 12th – The 2018 North Korea–United States summit was held in Singapore. It was the first summit between a United States President and a North Korean leader.

June 14th – The 2018 FIFA World Cup started in Russia (unfortunately NZ did not qualify… so, go England!)

June 18th – Mexico football fans may have caused an earthquake in Mexico city while celebrating the win over Germany.

June 21st – New Zealand’s Prime Minister Jacinda Ardern gave birth to her first child, Neve Te Aroha Ardern Gayford. “Te aroha” is a Maori waiata (song) about love and peace.

 

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

In June 2018, there were 642 research articles added to the Pubmed website with the tag word “Parkinson’s” attached (4180 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 8 pieces of Parkinson’s news

1. Immunosuppressants:

A population‐based case–control study of US Medicare beneficiaries (48,295 Parkinson’s and 52,324 controls) suggests that use of corticosteroids & inosine monophosphate dehydrogenase inhibitors might lower the risk of PD ( to read more about this, click here to read a SoPD post on this topic, and click here for the press release).

2. Nicotinamide riboside

Researchers report that increasing NAD+ levels (via the NAD+ precursor nicotinamide riboside) significantly reduces mitochondrial issues in cells from people with GBA-associated Parkinsons. In addition, nicotinamide riboside treatment prevents the age-related dopaminergic neuronal loss & motor decline in fly models of GBA-associated ( to read more about this and click here to read the press release).

3. Phospholipid Phosphatidylserine

Researchers find that flies with Parkinsons-associated PARKIN & PINK1 genetic mutations have circadian & sleep defects. Treating them with the phospholipid Phosphatidylserine helps to rescue those defects. ( to read more about this and click here to read the press release).

4. NLY01: A new GLP1 agonist 

A brain-penetrant Glucagon-like peptide-1 receptor agonist, called NLY01, protects against the loss of dopaminergic neurons & behavioral deficits in models of Parkinson’s, by blocking microglial-induced conversion of astrocytes to an A1 toxic state ( to read more about this and Click here to read an SoPD post on this topic and click here for another interesting commentary about this research).

5. Radotinib: A new c-Abl inhibitor

publish research suggesting that a new c-Abl inhibitor, Radotinib HCl, is neuroprotective in a preclinical model of Parkinson’s. Apparently better pharmacokinetic properties & safety profiles than Nilotinib! Developed by South Korean firm Ilyang Pharmaceutical, Radotinib is currently in phase III testing for chronic myeloid leukemia. Prof Ko & co seem very keen to clinically test Radotinib in Parkinson’s and related α-synucleinopathies ( to read the research report and click here to read a SoPD post on this topic).

6. Phase I results from Prothena

The results of the phase Ib clinical trial of PRX002/RG7935, an anti–alpha synuclein monoclonal antibody, in people with Parkinson’s has been published. 80 participants, observed over 24 weeks, looks safe & well tolerated. The Phase II efficacy trial is ongoing ( to read more about these results, Click here to read a SoPD post on the topic, and  to read an interesting editorial on the results).

7. Deep brain stimulation

New post hoc analysis suggests that deep brain stimulation in early Parkinson’s may slow rest tremor progression. These findings will be tested in an FDA–approved, phase III clinical trial evaluating DBS in early PD ( to read more and click here to read the press release).

8. Trodusquemine

Researchers have identified Trodusquemine (an aminosterol similar to squalamine) as an inhibitor not only of the initial phases of Parkinson’s-associated alpha synuclein aggregation but also the fibril-dependent secondary pathways. This result is particularly interesting because of the ability of trodusquemine to cross the blood-brain barrier (Squalamine does not!). “The present results suggest that this compound has the potential to be an important therapeutic candidate for Parkinson’s & related disorders” ( to read more about this and click here to read a SoPD post on this topic).

 

Basic biology news

  • Aptamers are short, single-stranded DNA or RNA molecules that can bind to a range of target proteins with high affinity and specificity. Aptamers are neither immunogenic nor toxic molecules – nucleic acids are not typically recognized by the human immune system as foreign agents. Aptamers are a promising alternative to antibodies. Now researchers have employed aptamers to block the toxic effects of the Parkinson’s-associated alpha synuclein protein in cells. System reduces α-syn aggregation & targets the α-syn for lysosomal degradation ( to read more about this).
  • New study unveils a microRNA-mediated mechanism of Glial cell-derived neurotrophic factor (GDNF) action, & suggests that targeting miRNAs could be a new therapeutic avenue Parkinson’s ( to read more about this).
  • New manuscript on biorxiv suggests that there are 14 human microglial subpopulations – noting intra- & inter-individual heterogeneity. These subpopulations display divergent associations with conditions like Parkinson’s & Alzheimer’s ( to read more about this).

  • New research explains how Parkinson’s-associated protein PARKIN and PINK1 interact, opening exciting new avenues to design PARKIN activators for clinical use (Click here to read more about this).
  • Powerful new tool for gene therapy approaches to correct lysosomal disorders: an adeno-associated virus that demonstrates broad distribution & remarkable ability to infect at low doses. This could be very useful against Parkinson’s (in particular GBA-associated PD?-  to read more about this).
  • New research suggests that intermittent fasting confers protection in brain autoimmunity by altering the gut microbiota. Given the suspected connections between the gut & brain in PD, could these findings have implications for Parkinson’s? ( to read more about this).
  • Channel-forming protein Sam50 (Tob55) has been found to regulate Parkinson’s-associated PINK1 & PARKIN-mediated mitophagy by controlling PINK1 protein stability and mitochondrial morphology ( to read more about this).
  • New study based on simulations suggests that water molecules may have an important role in the aggregation of intrinsically disordered Parkinson’s-associated protein alpha synuclein ( to read more about this).
  • Pro-inflammatory mediator & highly amyloidogenic protein S100A9 has been found to interact with Parkinson’s-associated protein alpha synuclein. S100A9 oligomers more toxic than those of α-syn, while co-aggregation of both reduces the toxicity of S100A9 ( to read more about this).
  • An increase in levels of Parkinson’s-associated LRRK2 protein suppresses autophagy & enhances Dectin-1–induced immunity in a mouse model of colitis (IBD). LRRK2 inhibitors decreased Dectin-1–induced TNF-α production – a new indication for LRRK2 inhibitors! ( to read more about this).

  • Researchers demonstrate that AKT signalling selectively regulates Parkinson’s-associated PINK1 based mitophagy in cell lines & human iPSC-derived neurons ( to read more about this).
  • New experimental tool that can simultaneously measure mitochondrial function, morphology & cell viability in dopamine neurons. Researchers detected mitochondrial dysfunction in single neurons with Parkinson’s associated genetic mutations (SNCA) ( to read more about this).
  • New modelling study suggests that bradykinesia may result from the concurrent effects of low DA levels & dysfunctional plasticity; perhaps training can be exploited in medicated subjects to improve levodopa treatment in Parkinson’s ( to read more about this).
  • New evidence that Parkinson’s-associated protein PARKIN may be involved in anti-viral response. Specifically, PARKIN negatively regulates antiviral immune responses against RNA and DNA viruses, by targeting TRAF3 for degradation ( to read more about this).
  • Researchers use the Drosophila Genetic Reference Panel to assess the affect of background on variability of locomotor dysfunction in a LRRK2 G2019S fly model of Parkinson’s. They identify 177 genes that drive wide phenotypic variation (19 top assoc. genes –  to read more about this).
  • Given all the attention on the links between diabetes and Parkinson’s at the moment, this seems kind of relevant: Gut microbiota modulate neurobehavior via changes in brain insulin sensitivity and metabolism. Mice with diet-induced obesity were given antibiotics and researchers observed decreased inflammation, improved insulin signaling in the brain & reduced signs of anxiety and depression (compared to obese mice not treated with antibiotics –  to read more about this).

  • Researchers provide key insights into the circuit mechanisms underlying the motor features of Parkinson’s & L-dopa induced dyskinesias – implications for developing targeted therapies. Following dopamine depletion in a rodent model of , the activity of indirect pathway medium spiny neurons was elevated only during periods of immobility, while the firing of direct pathway medium spiny neurons was dramatically and persistently reduced. They also identified a subpopulation of direct pathway medium spiny neurons with abnormally high levodopa-evoked firing rates, which correlated specifically with dyskinesia ( to read more about this).
  • Loss of Parkinson’s-associated protein LRRK2 leads to co-ordinated responses in protein translation & trafficking. Changes were not seen in mice with G2019S LRRK2 mutation, argue against a dominant negative role for the G2019S mutation ( to read more about this).
  • Miro is a motor/adaptor on the outer mitochondrial membrane. Removal of Miro is necessary for clearing dying mitochondria. Parkinson’s-associated alpha-synuclein accumulation results in increased levels of Miro protein. Removal of Miro rescues models of PD ( to read more about this).
  • Men are twice as likely to get Parkinson’s compared to women. A new study suggests sex-specific differences in the microglia – the helper/immune cells in the brain. Female microglia appear to be more neuroprotective! Implications 4 animal models of PD? ( to read more about this).
  • Post mortem analysis of brains from people who passed away with Parkinson’s reveals sex-specific differences. For example, lipid abnormalities & water content issues were found in the male PD subjects, but not in female PD subjects ( to read more about this).
  • The shape of what you grow dopamine neurons – for cell therapy in Parkinson’s – on and when you grow them on it appears to influence their final performance ( to read more about this).

  • Researchers report that reduced microglial glucocorticoid receptors activity in dopamine neurons can stimulate Toll-like receptor 9 activation & subsequent neurodegeneration. Could Dexamethasone (glucocorticoid receptor agonist) be useful? ( to read more about this).
  • Researchers report discovery of a new form of protein phosphatase PTEN – ‘PTEN-Long‘. This will have important implications for our understanding of the functioning of Parkinson’s-associated proteins PINK1 & Parkin in normal & disease states ( to read more about this).
  • A manuscript on Biorxiv suggests gut bacteria might be influencing L-dopa therapy in an unexpected way: bacterial tyrosine decarboxylase in the small intestine could explain the highly variable response to L-dopa. “Although the bacterial tyrosine decarboxylases have a higher affinity for tyrosine compared to L-DOPA, this does not affect their ability to convert L-DOPA to dopamine, nor does any inhibitor of the human decarboxylase” ( to read more about this).
  • Researchers identified two extracellular chaperones that directly bind to Parkinson’s-associated alpha synuclein oligomers. One of those chaperones – called clusterin – significantly reduces the toxicity of the oligomers ( to read more about this).
  • Researchers show that lipid-induced Parkinson’s-associated alpha synuclein protein can convert rapidly to mature fibrils at higher temperatures. Interesting: β-synuclein also forms protofibrils at higher temperatures ( to read more about this).

Disease mechanism

  • Parkinson’s-associated LRRK2 G2019S genetic mutation does not dramatically elevate the pathological burden of toxic alpha synuclein or neurodegeneration in neurons ( to learn more about this).
  • Parkinson’s-associated mitochondrial serine protease HtrA2 found to restricts the activation of inflammation (NLRP3 & AIM2 inflammasomes). Disruption of the protease activity of HtrA2 results in exacerbated NLRP3 & AIM2 inflammasome responses ( to read more about this).
  • Researchers find that mitochondrial populations are increased within axons of neurons in Parkinson’s, may represent attempt to maintain mitochondrial populations to facilitate continued transmission in the presence of neurodegeneration ( to read more about this).

  • Researchers report a novel variant form of Glial cell line-derived neurotrophic factor (GDNF) that exhibits increased dopamine turnover & brain bioavailability in primates (better than normal GDNF) ( to read more about this). This new report is follow-on research of this variant GDNF work in rodent models of Parkinson’s ( to read more about that preliminary research).
  • So smoking is bad for your health, but chronic nicotine improves cognitive & social impairment in mouse model of Parkinson’s (Thy1-aSyn mice). nAChR agonists may improve cognitive & social deficits debilitating non-motor aspects of PD ( to read more about this).
  • Researchers describe the ‘Disease Maps Project‘ () – an effort towards a community-driven computationally readable comprehensive representation of disease mechanisms. They provide a map of Parkinson’s ( to read more about this).
  • Are neuromelanin-containing organelle the “intracellular compartment of final destination for numerous molecules not degraded by other systems”? And could this play a role in Parkinson’s? Some scientists say ‘perhaps’ ( to read more about this).
  • It has previously been reported that TRIM28 regulates the levels & toxicity of Parkinson’s-associated alpha synuclein & Tau proteins. New study finds that depleting Trim28 in adult mice is well tolerated & reduces levels of alpha synuclein & tau ( to read more about this).
  • Micro RNAs are a group of powerful modulators of cellular activity. Researchers have now found that enhancing levels of a protein called Drosha, which controls micro RNA biogenesis, can rescue neurotoxic models of Parkinson’s ( to read more about this).
  • Parkinson’s-associated Lewy bodies commonly occur in Alzheimer’s, & Alzheimer’s pathology is frequent in PD. New research finds that increased age & APOEɛ4 status are risk factors for co-pathologies independent of neurodegenerative condition ( to read more about this).
  • A new genetic risk factor has been identified: LRP10 genetic variants in familial Parkinsons disease and dementia with Lewy bodies (Click here to read more about this).
  • Methylene blue, also known as methylthioninium chloride, is a medication & a dye. Researchers have found that it protects dopamine neurons in a neurotoxic model of Parkinson’s by upregulating brain‐derived neurotrophic factor (BDNF) ( to read more about this).

  • Montelukast, a leukotriene receptor antagonist used for asthma & seasonal allergies, demonstrates potential neuroprotective effects in a model of Parkinson’s by virtue of its anti-oxidant and anti-inflammatory actions ( to read more about this).
  • Could hyperglycemia (or high blood sugar) be influential in Parkinson’s? Researchers find loss of dopamine neurons in a rat model of long-term hyperglycemia ( to read more about this).
  • Researchers have developed a new intranasal formulation of DPP-4 inhibitor Omarigliptin for Parkinson’s. In rats: brain/plasma ratio 3.3 folds higher vs oral Omarigliptin group; 2.6 folds increase in brain glucagon-like peptide-1 concentration vs controls ( to read more about this).
  • New study illustrates how Parkinson’s-associated α-synuclein aggregates (oligomers) can affect the function of mitochondria in cells. Under physiological conditions, monomeric α-synuclein improves ATP synthase efficiency. Oligomeric α-synuclein… mmm, not so much – “Oligomers induce selective oxidation of the ATP synthase beta subunit and mitochondrial lipid peroxidation. These oxidation events increase the probability of permeability transition pore (PTP) opening, triggering mitochondrial swelling, and ultimately cell death” ( to read more about this).
  • Could viral infection be influential in the development of Parkinson’s? New research finds virus-like particles in 14/14 PD cases (only 1/7 controls) & enterovirus antigens present in PD brainstem neurons. Not associated with Lewy bodies ( to read more about this).

  • Researchers find that Parkinson’s-associated protein LRRK2 interacts with & regulates Receptor Interacting Serine/Threonine Kinase 1 (RIPK1). LRRK2 promotes RIPK1 activation, but interestingly LRRK2 inhibitors did not block associated effects ( to read more about this).
  • A novel interaction between Parkinson’s-associated proteins vacuolar protein sorting 35 ortholog (VPS35) & PARKIN has been reported. But PARKIN-mediated VPS35 ubiquitination does not promote the proteasomal degradation of VPS35 ( to read more about this).
  • p38 MAPK promotes mitochondrial dysfunction & neuronal death in the A53T alpha synuclein model of Parkinson’s by interacting with PD-associated PARKIN. Could p38 MAPK inhibitors be considered for PD? ( to read more about this).
  • New research finds that activation of NMDA receptors mediates iron accumulation via modulating iron transporters in a model of Parkinson’s. NMDA receptor inhibitors protected dopamine system & reduced iron levels in neurotoxin (6-OHDA) model of PD ( to read more about this).
  • Altered expression of genes involved in ganglioside biosynthesis in the substantia nigra dopamine neurons in Parkinson’s – these changes may increase the vulnerability of the neurons to degeneration in response to a variety of potential stressors ( to read more about this).
  • The results providing preclinical data for China’s 1st stem cell-based cell transplantation clinical trial for Parkinson’s has been published. “Grafts did not form tumors & produced variable but apparent behavioural improvement for at least 24 months” ( to read more about this).

  • DICER, an RNase III family enzyme, is required for processing of microRNAs. New research suggests that preventing microglial DICER degradation could be a novel strategy for controlling neuroinflammation in Parkinson’s  ( to read more about this).
  • Researcher demonstrate that the number of genetic mutations gained in the alpha synuclein gene in substantia nigra dopaminergic neurons occur more often in the brains of people with Parkinson’s than controls ( to read more about this).
  • New report suggests that disruption of Phospholipase PLA2G6 (a Parkinson’s-associated gene) results in similar defects to those observed upon loss of vps26 or vps35, or increased alpha synuclein – indicating that these defects may be common in PD ( to read more about this).
  • Partial reduction of peripheral M1 (‘inflamed’) macrophages reverses the motor issues observed in a mouse model of Parkinson’s by suppressing neuroinflammation & rescuing dopaminergic cell loss ( to read more about this).
  • Using brain tissue from nearly 1,000 postmortem cases, researcher found that two strains of herpes virus were far more abundant in the brains of folks with early-stage Alzheimer’s than in healthy controls. Implications for Parkinson’s? The findings were replicated in two additional, independent cohorts, but are viruses an active trigger, or were the brains of people already on the path towards Alzheimer’s simply more vulnerable to infection? ( to read more about this and Click here for the press release).

  • Corticobasal degeneration (CBD) is a clinically heterogeneous tauopathy, has overlaps w/ clinicopathologics & genetics of progressive supranuclear palsy (similar to Parkinson’s). New research indicates that severe TDP-43 pathology = distinct subtype of CBD ( to read more about this).
  • New research reveals how inhibition of lysosome membrane recycling leads to the accumulation of gangliosides. The build up of gangliosides contributes to neurodegeneration when lysosome recycling is disrupted. Implications for Parkinsons? ( to read more about this).
  • LINE‐1 is a mobile genetic element that can trigger oxidative stress‐induced DNA strand breaks. New research suggests that Engrailed protein protects dopamine neurons through the repression of LINE‐1. Implications for Parkinson’s? ( to read more about this).
  • a manuscript on BioRxiv suggests that pharmacologically increasing SIRT3 levels counteracts Parkinson’s-associated alpha synuclein-induced mitochondrial dysfunction by normalising mitochondrial activity ( to read the manuscript).

  • Researchers identify a mechanism of early assembly of Parkinson’s-associated alpha synuclein monomeric protein into elongated intermediates during first stages of aggregation (amyloid formation   to read more about this).
  • High dose of traditional Chinese medicinal Jia-Jian-Di-Huang-Yin-Zi (JJDHYZ) exhibits a neuroprotective effect in models of Parkinson’s ( to read more about this).
  • Parkinson’s-associated protein Parkin is recruited into complex I in response to TNFα (inflammatory) signaling. Parkin interacts with & mediates ubiquitination of RIPK1 to activate NF-κB signaling in cells stimulated by TNFα. NF-κB is key to stress response ( to read more about this).
  • Post-mortem brain analysis indicates age- & stage-dependent increase of the mitophagy marker phospho-ubiquitin in normal aging & Lewy body disease. Degree of co-existing signals & Parkinson’s hallmarks increased in early stages, but decreased in late stage ( to read more about this).

Clinical research

  • Interesting N=1 study (using a smartphone finger-tapping test) looking at tracking Parkinson’s over the course of the day. Lead author was the participant ( to read more about this).
  • Curious case study from Germany: 72yr man suspected of Parkinson’s; Acting out dreams nightly; DaTSCAN=reduced DA transporter density; Diagnosed in 2011 with PD; 6 months of melatonin treatment=gradual improvements & RBD absent; Additional DaTSCAN in 2015=no PD ( to read more about this).
  • Analysing 31 million user searches on Microsoft Bing over 18 months highlighted 700 users searching for Parkinson’s symptoms. Many components of cursor movements (including speed, direction changes,& tremors) could be used to suggest PD ( to read more about this).
  • Researchers post a manuscript on biorxiv reprint that uses machine learning on clinical data from the Parkinsons Disease Progression Marker Initiative. They find 3 distinct highly predictable subtypes. “Our analysis distinguished three distinct disease subtypes with highly predictable progression rates, corresponding to slow, moderate and fast disease progressors. We achieved highly accurate projections of disease progression four years after initial diagnosis…” ( to read the manuscript and click here to read a SoPD post on the topic).

  • Using music to improve gait dysfunction and quality of life for people with Parkinson’s. “Individualized rhythmic cueing can provide a safe & cost‐effective alternative to standard cueing that patients may want to use in their everyday lives” ( to read more about this).
  • Interesting imaging study of people with rapid eye movement (REM) sleep behaviour disorder (a common prodromal characteristic of Parkinson’s) points supports the idea of problems in peripheral autonomic nerves spreading to the brainstem ( to read more about this).
  • Ventral intermediate thalamic stimulation is effective in treating essential tremor and tremor-dominant Parkinson’s. Researchers provide insights into the underlying mechanisms ( to read more about this).
  • New study finds that folks with Parkinson’s exhibit reduced cheating behaviour when confronted with opportunities for dishonest gain ( to read more about this).
  • New manuscript on biorxiv reports that 360-degree turn test requires minimal time to administer & may be useful in mild-moderate Parkinson’s for distinguishing tremor-dominant and postural instability / gait difficulty subtypes ( to read the manuscript).
  • Using ultrasonography, researchers have found that the vagus nerve – the branches of nerves connecting the lungs, heart & gut to the brain – becomes smaller in people with Parkinson’s. Future biomarker? ( to read more about this).
  • Interesting overview of Parkinson’s in sub-Saharan Africa (Epidemiology, genetics, access to care, everything). Prevalence of PD: 7/100K in Ethiopia to 67/100K in Nigeria. Mean age at onset of 69.4 years. 0.03 neurologists per 100K pop compared 4.84 in EU ( to read more about this).

  • Spectral arc length measure (or SPARC) is a new method that provides valid measures of walking smoothness in people with Parkinson’s, calculated from trunk acceleration & angular velocity signals. Also sensitive to effect of PD medications ( to read more about this).
  • New research finds that Thiazolidinedione use was associated with a significantly reduced risk of Parkinson’s in people with newly-diagnosed diabetes mellitus ( to read more about this).
  • Curious association between specific metals with the risk & clinical characteristics of Parkinson’s. Copper level in blood are negatively correlated with cognitive scores in PD ( to read more about this).
  • More evidence of an association between diabetes & Parkinson’s – analysis of 8million+ individuals finds risk is greater in those with complicated Type 2 DM ( to read more about this and Click here for the press release).
  • Researchers show that excitability and plasticity abnormalities in primary motor cortex correlate with bradykinesia features in people with Parkinson’s. However, additional mechanisms sensitive to dopamine levels must also play a role ( to read more about this).
  • Parkinson’s-associated glucocerebrosidase (GBA) mRNA is diminished in the brain of Lewy body-related conditions and changes with progression in blood samples. Early PD & early-onset dementia with LBs = lowest GBA levels, which normalise in advanced PD ( to read more about this).
  • Interesting study looking at a pilot trial for personalised telemedicine for depression in Parkinson’s ( to read more about this).

  • Using the Weighted Protein-Protein Interaction Network Analysis pipeline, researchers attempt to better characterise the underlying genetic & functional architecture of idiopathic Parkinson’s. They nominate 17 novel candidate genes for sporadic PD ( to read more about this).
  • Researchers find an association between the incidence of Parkinson’s (& extrapyramidal symptoms) and the use of certain antidepressants, including duloxetine, mirtazapine, citalopram, & escitalopram ( to read more about this).
  • Researchers have a manuscript on biorxiv that finds elevated mind-wandering (associated with default mode network-visual network coupling) is an emerged feature of people who have hallucinations in Parkinson’s ( to read the manuscript).
  • Pathological & genetic analysis of person with PD that had a triplication of the Parkinson’s-associated gene SNCA (alpha synuclein) ( to read more about this).
  • Subthalamic nucleus deep brain stimulation & Levodopa independently lessened motor severity in Parkinson’s to a similar magnitude, but their combined effect is apparently greater than either treatment alone ( to read more about this).
  • A new study aimed at developing a targeted sequencing approach using a 127 genes involved in movement disorders like Parkinson’s highlights some unexpected genotype-phenotype correlations & 49 novel pathogenic variants in a cohort of 378 people ( to read more about this).
  • New study reports that postural instability is more common in atypical parkinsonism than Parkinson’s (PD). Tandem gait performance can be used to discriminate between atypical parkinsonism & PD ( to read more about this).
  • Could subthalamic theta activity be a novel subcortical biomarker for obsessive compulsive disorder in Parkinson’s? A deep brain stimulation study suggests so ( to read more about this).
  • Analysis of a survey of 1,775 individuals from 11 European countries on self‐reported access to care/services for Parkinson’s makes for interesting reading ( to read more about this).

  • Comparatively analysis of 39 people with Progressive Supranuclear Palsy, 31 with Parkinson’s & 58 controls suggests phosphorylated-tau/total-tau ratio (in cerebrospinal fluid) could be helpful in the early differential diagnosis between PSP & PD ( to read more about this).
  • New research confirms findings from previous studies suggesting a role for GCase in GBA-associated Parkinson’s, as well as sporadic PD & dementia with Lewy bodies. “results show decreased GCase activity in brains of Parkinson’s and DLB patients with and without GBA variants, most pronounced in the substantia nigra” ( to read more about this).
  • Genome-wide association studies using DNA from more than 200,000 people with 25 brain-associated disorders finds Parkinson’s, Alzheimer’s, & Multiple Sclerosis show showed little to no correlation with other brain disorders & with each other ( to read more about this).
  • Greater vigilance needed with impulse control disorder (ICD) in Parkinson’s. Large longitudinal study finds of 306 PwPs without ICDs at baseline, the 5-year cumulative incidence of ICDs was 51% in dopamine agonist ‘ever’ users vs 12% in ‘never’ users. Conclusion of the study: “ICDs were strongly associated with dopamine agonist (DA) use with a dose-effect relationship; both increasing duration and dose were associated with ICDs. ICDs progressively resolved after DA discontinuation” ( to read more about this).
  • Researchers find that levels of uric acid & uric acid/creatinine in the early & medium stages of Parkinson’s were significantly higher than in the advanced stages. UA & UA/Cr levels are negatively correlated with the stages of PD ( to read more about this).

 

Clinical trial news

  • The results of the phase Ib clinical trial of PRX002/RG7935, an anti–alpha synuclein monoclonal antibody, in people with Parkinson’s has been published. 80 participants, observed over 24 weeks, looks safe & well tolerated. The Phase II efficacy trial is ongoing ( to read more about these results, Click here to read a SoPD post on the topic, and  to read an interesting editorial on the results).

  • A follow-up report on the Phase II clinical trial of Exenatide in Parkinson’s has just been published. It is a deep dive analysis of the data. Conclusion: ‘Exenatide may exert independent effects on mood dysfunction’ ( to read this report).
  • A double-blinded, placebo-controlled, randomised clinical study finds that Automated Peripheral Stimulation (AMPS) decreased gait variability in subjects with Parkinson’s & freezing of gait ( to read more about this).
  • The results of a randomised controlled clinical study investigating the use of footstep sounds as rhythmic auditory stimulation for gait rehabilitation in Parkinson’s has been published ( to read more about this).
  • Voyager Therapeutics announced FDA Regenerative Medicine Advanced Therapy (RMAT) designation has been granted for their experimental VY-AADC gene therapy treatment for Parkinson’s. RMAT was established under the 21st Century Cures to speed progress ( to read more about this).

Other news

  • The AETIONOMY project () plans to change classifying of neurodegenerative conditions (like Parkinson’s and Alzheimer’s) based on their disease mechanisms rather than clinical symptoms. They hope to propose new taxonomies in November ( to read more about this).
  • A very interesting discussion on the challenges facing ethics and institutional review boards for the first-in-human stem cell clinical trials for Parkinson’s. The International Society for Stem Cell Research developed a set of questions to cover the issues ( to read more about this).
  • Neuroscience biotech firm Axovant announces worldwide license deal for investigational gene therapy treatment (OXB-102, now AXO-Lenti-PD) for Parkinson’s from Oxford BioMedica. The predecessor product, ProSavin®, successfully completed a Phase 1/2 study ( to read more about this).

  • Pfizer has announced that it is expanding its venture investing with $600 million commitment to Pfizer Ventures. Approximately 25% of the new funding will be dedicated to neuroscience – hope for Parkinson’s? ( to read the press release).
  • The Michael J Fox Foundation has released the Spring/Summer edition of The Michael J. Fox Foundation’s newsletter. Interesting piece on page 12-13 on the gut ( to read more about this).
  • The Parkinson’s Institute and Axial Biotherapeutics announce a new collaboration to target gastrointestinal metabolites that may contribute to Parkinson’s ( to read more about this).
  • Apparently the Apple watch can now monitor tremors & dyskinesia in people with Parkinson’s continuously throughout the day (not an endorsement/advert – just a curious mind –  to read more about this).

  • The Parkinson’s movement website has changed – a wealth of useful information dealing with Parkinson’s – what an incredible website! Understand, Participate, Contribute – a great message ( to see the new website).
  • No surrender. Rock band ‘Judas priest‘ have launched the Glenn Tipton Parkinson’s Foundation to honour their guitarist who has been diagnosed with Parkinson’s. Sales from all T-shirts go to PD research ( to read more about this).
  • “Coping with cognitive impairment in people with Parkinson’s and their Carers: A qualitative study” ( to read more about this).
  • Interesting news regarding where the Michael J Fox Foundation are putting their research funding in the latest round of awards ( to read more about this).

  • In addition 2 acquiring foliglurax from Prexton Therapeutics earlier this year, Lundbeck has just added another Parkinson’s-focused drug to their pipeline. Lu AF76432 is being developed for treating OFF-state & dyskinesia issues in people with advanced PD ( to read the press release).
  • Interesting commentary highlighting new resources available to help the wider Parkinson’s support network (PwPs, carers, volunteers, partners and friends) with an interest in exercise ( to read more about this).
  • Interesting appraisal of the 2015 US FDA approval for earlier deep brain stimulation intervention in Parkinson’s ( to read more about this).
  • Appello Pharmaceuticals raised $10.5 million to fund development of a new treatment (a positive allosteric modulators of metabotropic glutamate receptor subtype 4 – similar to foliglurax) for Parkinson’s ( to read the press release).

 

Review articles/videos

  • Interesting piece on organelles – 3D cultures of stem cells – and their use in “organs-on-chips” assays. These are microfabricated devices that could provide useful tools for quickly testing new drugs for conditions like Parkinson’s on a personalised basis ( to read more about this).
  • Interesting analysis & discussion regarding the re-purposing of old drugs to deal with the NON-motor aspects of Parkinson’s. Could old NMDA antagonists (such as ketamine) help to modulate depression & psychiatric symptoms? ( to read more about this).
  • Is Parkinson’s disease a lysosomal disorder? Researchers argue that Parkinson’s is a complex genetic disorder involving partially penetrant mutations that converge on lysosomal cellular clearance pathways ( to read the review).

  • Interesting review of protein oligomerization in the development of Alzheimer’s & Parkinson’s ( to read more about this).
  • Interesting report from a multidisciplinary symposium on unmet needs and future directions to maintain cognitive health in Parkinson’s. Covering 9 topics – everything from exercise to nutrition – lots of food for thought ( to read more about this).
  • “The validity of Braak staging and its relationship to various subtypes of Parkinson’s warrants further studies”. An interesting discussion from Kurt Jellinger regarding the staging of how PD develops – “Braak staging system is valid for Parkinson’s patients with young onset, long duration with motor symptoms, but not for others, e.g., late onset and rapid course PD” ( to read more about this).

  • Interesting short review of the role & mechanism of Parkinson’s-associated PARKIN protein in cancer. “The association between PD & cancer risk appears to be complex and may be linked to factors such as ethnicity” ( to read more about this).
  • Interesting review of current therapeutic strategies for targeting neurodegenerative protein misfolding disorders, such as Parkinson’s ( to read more about this).
  • Interesting open access review of mechanisms of protein toxicity in neurodegenerative conditions, like Alzheimer’s, Parkinson’s, and Huntington’s ( to read more about this).

 

  * * * * * * * * * * * *

And there it is, just some of the highlights from June 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 July!

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.

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