# # # # 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 July 2020. The post is divided into seven parts based on the type of research: Basic biology Disease mechanism Clinical research New clinical trials Clinical trial news Other news Review articles/videos # # # #

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What happened in July 2020?

In world news:

July 1st – With the introduction of the new national security law, academics in Hong Kong expressed concern about being able to recruit talented researchers and to import critical high tech equipment (due to international sanctions – click here to read more about this).

July 16th – Six year old Bridger Walker gained social media fame after saving his sister from being attacked by a charging dog. Bridger was bitten several times on the head and face, requiring 90 stitches. Celebrities praised his brave actions:

 

July 17th – Capt Sir Tom Moore was knighted – what a legend! (Click here to read more about this).

July 25th – A record high temperature of 21.7°C (71.1°F) is recorded on the Arctic archipelago of Svalbard, according to the Norwegian Meteorological Institute.

July 31st – Researchers reported that human sperm do not swim the way we thought they did (rather rolling and lopsided tail flicks keep the cells moving in a straight line – click here to read more about this).

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

In July 2020, there were 753 research articles added to the Pubmed website with the tag word “Parkinson’s” attached (6058 for all of 2020 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 Parkinson’s news

1. The Stanford Parkinson’s Disease Plasma Study:

Researchers in California reported the results of their safety study exploring young plasma infusions in Parkinson’s. The study involved 15 participants, and it found that the treatment was safe, feasible, well tolerated and warranted “further therapeutic investigations in PD” (Click here to read more about this and click here to read a SoPD post on this topic)

2. The Kyoto cell transplantation study team published more preclinical data:

Researchers in Kyoto who are conducting the Kyoto cell transplantation clinical trial have reported more of their preclinical data from studies of induced pluripotent stem cell-derived dopamine progenitor cells (including tumorigenicity, toxicology, & biodistribution), plus more work in models of Parkinson’s (Click here to read more about this and click here to read an old SoPD post about the Kyoto trial).

3. A report on the projected future economic burden of Parkinson’s in the U.S

Researchers finds Parkinson’s resting tremor can be divided into 3 partially overlapping phenotypes, based on the dopamine-response; may be associated with different underlying pathophysiological mechanisms (Click here to read more about this).

5. An overview of the clinical drug development pipeline for Parkinson’s

Indepth analysis of the clinical trial landscape from PD research (super) advocates Kevin McFarthing (@InnovationFixer) Sue Buff (@SueBCal1), & Gary Rafaloff (@grafaloff) and The Cure Parkinson’s Research team, provides an overview & analysis of 2019-2020 clinical drug development pipeline for Parkinson’s – both symptomatic & disease modifying. The study explored data from 145 Parkinson’s clinical trials that were ongoing during 2019-2020, breaking them down into phase & agent type to give the PD community a broad view of the clinical research landscape. Some very interesting trends appear in the data – such as 57 trials (39%) of all the trials were focused on long-term disease modifying therapies. (Click here to read more about this).

# EDITORIAL NOTE:  Change is a good thing – evolving old ideas based on current needs, etc. That said, I am seeking feedback regarding these monthly review posts. This website has changed considerably over the years, and all of those changes have come from reader input. So I am asking what works? What doesn’t work? What is missing? What would be useful? I am currently concerned that there is too much information presented in these monthly reviews. Good for psychology yes, but is it difficult to sort though? Perhaps this is what readers are looking for? Any thoughts in the comments (or contact me directly) would be greatly appreciated. #

 

Basic biology news

• Nurr1 performs its anti-inflammatory function by directly binds to the RasGRP1 intron & regulating expression in neuro-inflammation. Also, RasGRP1 modulates the Ras-Raf-MEK-ERK signaling cascade in LPS-induced inflammation (Click here to read more about this).
• Researchers report that the major virulence factor of Rift Valley fever virus – the protein NSs – forms filamentous structures in the brain of mice & affects mortality. “NSs structural arrangements exhibit characteristics typical for amyloids”..”our results demonstrate that viruses can encode amyloid-like fibril-forming proteins & have strong implications for future research on amyloid aggregation” Implications for Parkinson’s here? (Click here to read more about this).

• Researchers report single-vesicle imaging study that reveals lipid-selective & step-wise membrane disruption by Parkinson’s-associated α-synuclein (monomeric – click here to read more about this and click here to read the press release).
• Researchers designed & evaluated bi-functional iron chelators for protection of dopaminergic neurons from toxicants; SK4 was characterized further. “Data strongly support the role of iron in dopaminergic neurotoxicity” (Click here to read more about this).
• Researchers report that neurodegeneration caused by the Parkinson’s-associated LRRK2 G2019S mutation is highly influenced by dietary amino acid levels in adult Drosophila & in mammalian neuron cultures (Click here to read more about this).
• Researchers report several structurally diverse non-steroidal anti-inflammatory drugs can modulate the orphan nuclear receptor Nurr1 – a promising target in Parkinson’s treatment (Click here to read more about this).
• Researchers have a bioRxiv manuscript suggesting that LRRK2 G2019S mutation alters astrocyte-to-neuron communication (via extracellular vesicles) & induces neuron atrophy in a human iPSC-derived model of Parkinson’s (Click here to read more about this).

• Researchers have a new bioRxiv manuscript presenting “AI-Photoswitchable Screening” (AI-PS) – a novel CRISPR-based screening platform capable of classifying a range of mammalian subcellular morphologies. Proof-of-concept explores Parkinson’s biology (Click here to read more about this).
• Researchers report zebrafish lacking Cerebral Dopamine Neurotrophic Factor (CDNF). Their findings are “informative for dissecting the diverse functions of this poorly understood factor” (Click here to read more about this).
• Researchers have a new bioRxiv manuscript exploring the measuring the iron content of dopaminergic neurons in substantia nigra using MRI relaxometry. Implications for early detection of Parkinson’s? (Cick here to read more about this).
• Nano-imaging trace elements at organelle levels in substantia nigra overexpressing α-synuclein to model Parkinson’s. Results suggest metal dyshomeostasis in discrete cytoplasmic regions (Click here to read more about this).
• Researchers report Parkinson’s-associated LRRK2 is activated & phosphorylates Rab8A upon endomembrane damage in macrophages; G2019S or R1441C mutation show accumulation of damaged endolysosomes in macrophages (Click here to read more about this).
• Researchers report in vivo synthesis of curli may contribute to known complications of enteric infections; cross-seeding interactions may occur between pathogen-produced amyloids & host amyloidogenic proteins (Click here to read more about this and click here for the associated press summary).

• Researchers have a new bioRxiv manuscript that suggests L-type voltage-gated Ca2+ channels are dynamically, locally, & sexually divergent…ly regulated on dopamine neuron axons (Click here to read more about this).
• Parkinson’s-associated LRRK2 plays a context‐dependent role in promoting Wnt signaling during zebrafish development (Click here to read more about this).
  
• Researchers reveal that the ubiquitin signal is sufficient for mitophagy & that Parkinson’s-associated PINK1 & Parkin are unnecessary for autophagy activation per se. The critical autophagy adaptor OPTN forms a complex with ATG9A vesicles (Click here to read more about this and click here to read the associated press release).
• Researchers report N-Acetylcysteine (NAC) nanocarriers protect against oxidative stress in an in vitro model of Parkinson’s (Click here to read more about this).
• Researchers have a new bioRxiv manuscript presenting a comprehensive description of the metabolomic changes in a PARKIN/PARK2-KO iPSC model of Parkinson’s; highlighting bioactive metabolites & altered mitochondrial & energy metabolism (Click here to read more about this).
• Time to explore hepcidin mimetics in Parkinson’s? Researchers report a gene therapy hepcidin treatment protected models of Parkinson’s by reducing iron & α-synuclein accumulation, & promoting clearance of α-synuclein (Click here to read more about this).
• Researchers report that Parkinson’s-associated LRRK2 regulates Frizzled3. Both LRRK1/2 are required for the proper guidance of dopamine neuron axons during development (Click here to read more about this).

• Starting to think that everything aggregates in dopamine neurons…  Researchers have a bioRxiv manuscript suggesting that uranium aggregates in the cytoplasm of dopamine neurons (post continuous exposure to soluble uranyl at non-cytotoxic concentration – click here to read more about this).
• Parkinson-linked Vps35 R524W mutation impairs the endosomal association of retromer and induces α-Synuclein aggregation (Click here to read more about this).
• Looking for all the hot sites of Parkinson’s-associated α-synuclein in amyloid fibril formation? (Click here to read more about this).
• Researchers have a bioRxiv manuscript suggesting a possible molecular mechanism to account for the different pathologies induced by different Parkinson’s-associated α-synuclein strains (Click here to read more about this).
• Researchers present preclinical data that targeting striatal cholinergic interneuron with channel-specific modulators may provide therapeutic approaches for alleviating L-DOPA-induced dyskinesia in Parkinson’s (Click here to read more about this).
• PD-on-chip: Researchers have a bioRxiv manuscript presenting an α-syn fibril-induced Parkinson’s model-on-chip representative of the substantia nigra area of the brain containing dopaminergic neurons, astrocytes, microglia, etc. (Click here to read more about this).
• A new bioRxiv manuscript suggests the developmentally important transcription factor for dopamine neurons, Nato3, controls a transcriptional network to maintain mitochondrial structure & function in adult DA neurons (Click here to read more about this).
• Further investigations of stearoyl-CoA desaturase inhibition reducing Parkinson’s-associated alpha-synuclein toxicity & restoring growth in in vitro models (Click here to read more about this).

• Researchers report further data that ketamine may be useful in reducing the development of L-DOPA-induced dyskinesia in rodent models of Parkinson’s (Click here to read more about this).
• “Membrane-bound α-synuclein is conformationally dynamic, exquisitely sensitive to lipid/protein composition, enabling the protein to carry out its function” Parkinson’s-associated α-syn is more dynamic at the membrane interface than previously thought (Click here to read more about this).
• Integrative analysis of gene expression & regulatory network interaction data reveals the Protein Kinase C (PKC) family of serine/threonine receptors as a significant druggable target for Parkinson’s (Click here to read more about this).
• Could β‐Synuclein play a role in the neurodegeneration associated with Parkinson’s (via its interaction with dopamine metabolites)? (Click here to read more about this).
• Researchers explored modulators of Parkinson’s-associated α-syn & tau aggregation/internalization found that anle138b & fulvic acid decrease α-syn & tau aggregation, EGCG reduces α-syn aggregation, & dynasore reduces tau internalization (Click here to read more about this).

Disease mechanism

• Long-term continuous cervical spinal cord stimulation reported to exert neuroprotective effects (behavioral & histological benefits) in model of Parkinson’s (Click here to read more about this).
• Dopaminergic neurodegeneration induced by Parkinson’s disease-linked G2019S LRRK2 is dependent on kinase and GTPase activity (Click here to read about this).
• Following interesting pilot clinical study results with sargramostim (GM-CSF) in Parkinson’s, researchers now present data on a long-acting version of GM-CSF in a mouse model of PD. Better performance than GM-CSF suggest PDM608 as a candidate for PD (Click here to read more about this and click here to read an old SoPD post on this topic).
• Researchers have a bioRxiv manuscript presenting a novel, selective & reversible MAO-B inhibitor, KDS2010 that has a potent therapeutic effect 3 Parkinson’s models (6-OHDA, MPTP, & A53T). Moreover, littel toxicity or side-effect in non-human primates (Click here to read more about this).
• Swedish biotech firm IRLAB Therapeutics have published data on the development of IRL752 a new phenyl-pyrrolidine derivative with regio-selective CNS transmission-enhancing properties. Being targeted towards axial motor and cognitive deficits in Parkinson’s (Click here to read more about this and click here to read the press release).

• Could erythrocyte-derived vesicles containing α-synuclein provide a new perspective on Parkinson’s pathogenesis by messing with astrocytic glutamate homeostasis? (Click here to read more about this).
  
• Researchers report a nano-scale exploration of extracellular space features relevant for the Parkinson’s-associated α-synuclein propagation hypothesis & they suggest matrix manipulation could be a disease-modifying strategy (Click here to read more about this).
• Researchers have a bioRxiv manuscript suggesting transplanted ES cell-derived dopamine neurons survived >10 months in 3 immunosuppressed primates; no tumors; partially compensate the loss of dopamine (Click here to read more about this).
• Researchers report that exogenous treatment with neurodegenerative disease-associated protein aggregates (eg alpha synuclein in Parkinson’s) results in poor induction of the heat shock response in neuronal cells in vitro (Click here to read more about this).
• New research reports diabetes in mice promotes striatal oxidative stress, alters dopamine neurotransmission, & increases vulnerability to neurodegenerative damage leading to motor impairment. Implications for Parkinson’s? (Click here to read more about this).
• Prolonged induction of metallothionein – endogenous metal detoxifying protein – combats Parkinson’s-associated α-synuclein toxicity (in aged transgenic Caenorhabditis elegans – click here to read more about this).
• Researchers discuss the importance of administration route for genetically modified macrophages accomplishing targeted gene delivery to the inflamed brain in transgenic Parkinson’s (Parkin Q311X(A)) mouse model (Click here to read more about this).
• Researchers conducted a systematic review of Helicobacter pylori in idiopathic Parkinson’s, & they make some interesting conclusions (Click here to read more about this).

• ATP-sensitive potassium channel blocker, glibenclamide, has neuroprotective effect against neurotoxin Parkinson’s model (via anti-inflammatory & anti-apoptotic pathways – click here to read more about this).
• Researchers report suppression of microglial activation in LPS-induced neuroinflammation & MPTP-induced models of Parkinson’s by the PDE10A inhibitor MP-10 (PF-2545920 – click here to read more about this).
• A new study reports Parkinson’s-associated α-synuclein induces progressive changes in brain microstructure & sensory-evoked brain function that precedes locomotor decline. Longitudinal MR imaging of α-syn fibril mouse model (Click here to read more about this).
  
• Alpha-lipoic acid mediates clearance of iron accumulation by regulating iron metabolism in a neurotoxin (6-OHDA) model of Parkinson’s (Click here to read more about this).
• Researchers report the classification of α-synuclein-induced changes in the AAV α-synuclein rat model of Parkinson’s using electrophysiological measurements of visual processing (Click here to read more about this).
• KM-819 is a novel FAS-associated factor 1 inhibitor being clinically tested by Kainos Medicine. Now Korean researchers report neurorestorative effects of delayed KM-819 treatment in an MPTP Parkinson’s model, using [18F]FE-PE2I PET analysis (Click here to read more about this).

• Researchers report neuroinflammation is associated with infiltration of T cells in brains of Lewy body disease patients & α-synuclein (Thy1 promoter line 61) transgenic models of Parkinson’s (Click here to read more about this).
• Using transgenic mice expressing hyperactive Nlrp3 mutations in the dopamine neurons alone, researchers report neuronal inflammasome activity may contribute to neuroinflammation observed during normal aging & the progression of Parkinson’s (Click here to read more about this).
• Researchers report that both oral & discrete intracerebral administration of a µ opioid receptor agonist (but not of an antagonist as long thought) ameliorated L-DOPA induced dyskinesias in the bilateral MPTP-lesioned primate model of Parkinson’s (Click here to read more about this).
• A bioRxiv manuscript using a Mendelian randomisation approach explores the ‘druggable genome’ and suggests drug targets for Parkinson’s – more support for metformin (Click here to read more about this).
• In a model of Parkinson’s “injection of HMGB1 competitive inhibitor protein HMGB1 A Box & the Ethyl pyruvate which inhibit the release of HMGB1 from cells, restored the number of dopaminergic neurons & TH+ fibers in the SN & striatum” (Click here to read more about this).
• T-006, a derivative of tetramethylpyrazine & a Chinese medicinal component, reported to have neuroprotective & neurogenic effects in models of Parkinson’s (Click here to read more about this).
• Researchers report microglia, inflammation & gut microbiota responses in a progressive MPTP primate model of Parkinson’s. Small N study, but sex differences were observed in inflammation, microbiota diversity, etc. Also interesting to see INmune Bio‘s novel soluble TNF inhibitor XPro1595 also being tested in this study. Administered every 3 days starting 11 weeks after the initiation of MPTP (Click here to read more about this).

• Researchers present a Parkinson’s CircRNAs resource & reveal a link betwn circSLC 8A1 & oxidative stress. circSLC 8A1 is increased in the substantia nigra of PD; levels also increased in vitro by paraquat & decreased by simvastatin (Click here to read more about this and click here for a summary of the study).
• “Autophagy-dependent removal of α-synuclein: a novel mechanism of GM1 ganglioside neuroprotection against Parkinson’s” (Click here to read more about this).
  
• A bioRxiv manuscript suggests a role for Parkinson’s-associated LRRK2 in modulating iron uptake & storage in response to proinflammatory stimuli in microglia. Increase in iron deposition in microglia in G2019S mice post LPS (Click here to read more about this).
• Glycomics & proteomics study of aging & Parkinson’s in human brain reports upregulation of extracellular matrix structural components (collagens, proteoglycans & glycosaminoglycan binding molecules) & defects in iron metabolism enriched in PD brains (Click here to read more about this).

Clinical research

• New medRxiv manuscript outlines the development & validating a new web-based tapping test for long term monitoring of distal bradykinesia in Parkinson’s (Click here to read more about this and click here to see the website).
• A large cohort (n=1676) study of familial & sporadic early-onset Parkinson’s finds the 1st evidence of an SNCA duplication & LRRK2 p.N1437D variant in China. Provides “insight into the genetic spectrum & clinical manifestations of Parkinson’s in mainland China” (Click here to read more about this).

• Under represented communities: Researchers have a bioRxivmanuscript confirming that rare Parkinson’s-associated LRRK2 pathogenic variants reported in Caucasians, Asians & persons of mixed ancestry are absent in West Africans (Click here to read more about this).
  
• Under represented communities: Addressing knowledge gaps in Parkinson’s: a report on the Movement Disoder Society’s Centre-to-Centre initiative to improve PD services in Lao People’s Democratic Republic (Laos – click here to read more about this).
• Under represented communities: Lux-GIANT Consortium colleagues present the “Genetic Architecture of Parkinson’s in India” (GAP-India) project which aims to develop one of the largest clinical/genomic bio-bank for PD in India. Currently working on recruiting 10,200 PD patients (& 10,200 controls) by the end of 2020. Filling “a critical gap in knowledge regarding the genetic origins of PD, by leveraging the population diversity afforded by as a yet unaddressed population” (Click here to read more about this).
• Under represented communities: A study in an Indian early onset PD cohort identified 16 novel variants in known PD genes & provides some evidence for higher genetic burden. 1st report of VPS35 p.D620 N mutation from the Indian population (Click here to read more about this).

• Researchers explore Parkinson’s case ascertainment in prospective cohort studies using a combination of multiple health information resources (Click here to read more about this).
• Large‐scale (n=3402 PD participants + 655 controls) full GBA1 gene screening in Parkinson’s in the Netherlands. Conclusion: Dutch PD patients display one of the largest frequencies of GBA1 variants reported so far (15% vs 6.4% in controls). 18 new variants (Click here to read more about this).
• Researchers find that a modified PDQ-39 is suitable for use in epidemiological studies exploring Parkinson’s in English-, Afrikaans-, Setswana-, & Zulu-speaking South African communities (PDSQ needs to be further modified – click here to read more about this).
• Researchers report that the patterns of striatal dopaminergic denervation may have prognostic implications in patients with early-stage Parkinson’s (Click here to read more about this).
• DaTSCAN imaging in early versus mid & late onset Parkinson’s: Longitudinal data from the PPMI study (Click here to read more about this).
• Researchers have a new medRxiv manuscript presenting high-throughput & hypothesis-free approaches (GWAS, PRS & MR) that converge on a genetic link between Parkinson’s with CSF Ab42 & APOE (Click here to read more about this).
• Researchers have a new medRxiv manuscript that points towards another Parkinson’s-associated gene (in addition to LRRK2) ABCB1 being one of 7 novel plausible inflammatory bowel disease-causing gene (Click here to read more about this).

• Researchers report long-term quality of life after staged deep brain stimulation procedures for Parkinson’s (including STN vs GPi; first vs second lead) to help decision making process (Click here to read more about this).
• Interesting development on the whole “PTBP1 astrocyte-to-dopamine neuron” story: researchers report using human neuron-type functional networks & GWASs to model vulnerability in Alzheimer’s, & they highlight sig. increase in PTBP1 in AD brains. BUT, they also report that silencing PTBP1 increases total SNCA (the gene encoding Parkinson’s-associated alpha synuclein) RNA levels & reduces tau exon 10 splicing. Overexpression of PTBP1 increased the 3R/4R ratio for human tau in htau PAC mice (Click here to read more about this).
  
• Researchers report bi-allelic variants in PNPLA6 possibly associated with Parkinson’s-like features in addition to spastic paraplegia phenotype (Click here to read more about this).
• New bioRxiv manuscript presents GWAS data suggesting 5 independent risk loci for Lewy body dementia (LBD), whereas GWGA tests implicate mutations in the GBA gene. Interesting that LBD shares risk profiles & pathways with Alzheimer’s & Parkinson’s (Click here to read more about this).
• Nationwide cohort study (3,908,687 Korean males) finds post smoking cessation weight gain in males did not offset the protective impact of smoking on Parkinson’s development, although overall weight gain predicted an increased risk of PD (Click here to read more about this).

• Researchers present a  new contactless method for measuring Parkinsons hand bradykinesia (Click here to read more about this).
• New study suggests altered interhemispheric synchrony in Parkinson’s patients with levodopa-induced dyskinesias. Uncoordinated inhibitory control over motor circuits may underlie the neural mechanisms of dyskinesias (Click here to read more about this).
• New study reports rs12411216 SNP (a candidate in a distal regulatory element of the GBA gene) was significantly associated with Parkinson’s with mild cognitive impairment. It was also found to be associated with GBA expression (Click here to read more about this).
• Researchers analysed standard 10-s ECG recordings of participants in the Honolulu Asia Aging Study, & found that electrocardiographic changes predate Parkinson’s onset (Click here to read more about this).
• Researchers report a novel mutation in the PARK-2 gene in a patient with early-onset Parkinson’s (Click here to read more about this).
• Researchers in Hawaii report that genome-wide epigenetic analyses in Japanese immigrant plantation workers with Parkinson’s & exposure to organochlorines reveals possible involvement of glial genes & pathways involved in neurotoxicity (Click here to read more about this).

• Significantly elevated in vitro kinase activity in peripheral blood mononuclear cells of Parkinson’s-associated LRRK2 G2019S carriers; also significant increase in pS935/LRRK2 in idiopathic PD (Click here to read more about this).
  
• Researchers report that Parkinson’s‐associated sensory neuropathies/pain may in part be caused by glucosylceramide accumulation, raising possibility of reducing PD pain & sensory loss by glucocerebrosidase substituting/refolding approaches (Click here to read more about this).
• Validation of a UPDRS-/MDS-UPDRS-based definition of functional dependency for Parkinson’s (Click here to read more about this).
• Long‐term (avg 6.3 yrs) follow‐up of the “Parkinson’s Associated Risk Syndrome” cohort finds a high rate of conversion to clinical PD in subjects who 1.) had abnormal dopamine transporter imaging at baseline or 2.) developed abnormal imaging during study (Click here to read more about this).
• Researchers report that both HDAC6 & its phosphorylated form localise with pathological protein aggregates (α-synuclein-positive Lewy bodies in Parkinson’s, Papp–Lantos bodies in Multiple system atrophy (MSA) , & phospho-tau-neurofibrillary tangles in Progressive supranuclear palsy (PSP) – click here to read more about this).
• Researchers dissect the genotype–phenotype correlates in a large Italian Parkinson’s cohort (n=874). 36 variants were detected in 14.3%. GBA‐associated PD had lowest β‐GCase activity + earlier & more frequent occurrence of several nonmotor symptoms (Click here to read more about this).

• Neww medRix manuscript suggests that the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet may postpone onset of Parkinson’s, maybe more in women (Click here to read more about this).
• The Michael J Fox foundation LRRK2 Cohort Consortium report regular nonsteroidal anti‐inflammatory drugs (NSAIDs) use may be associated with reduced penetrance in LRRK2 ‐associated Parkinson’s. N=259; odds ratio 0.34; 95% CI, 0.21–0.57; both path & risk variants (Click here to read more about this).
  
• New study explores prediction of age at onset in Parkinson’s, using objective specific neuroimaging genetics based on a sparse canonical correlation analysis (Click here to read more about this).
• Drug-induced parkinsonism is different to classical idiopathic Parkinson’s, but a new study reports that they share some functional neural substrates (the insular cortex, occipital cortex, & cerebellum – click here to read more about this).
• The physical significance of acoustic parameters & its clinical significance of dysarthria (speech issues) in Parkinson’s (Click here to read more about this).
• New medRxiv manuscript suggests a lack of evidence to support a role for rare damaging nonsynonymous NUS1 variants in Parkinson’s. Additional non-European large-scale familial & case-control studies required (Click here to read more about this).
• “Towards accurate & unbiased imaging-based differentiation of Parkinson’s, progressive supranuclear palsy (PSP) & corticobasal syndrome“. Their results “support the use of statistical classification approaches for differential diagnosis of parkinsonian disorders”, but “classification accuracy can be affected by group size, age, sex & movement artefacts”. (Click here to read more about this).
• Researchers conducted genetic analysis of an early-onset Parkinson’s cohort (n=176) & found limited evidence to support a significant role for genetic variations in RAB39B as a contributory factor (Click here to read more about this).

• Researchers report knowledge about overlapping coping strategies is relevant to the implementation of strategies to promote active & healthy coping in study of 162 people with Parkinson’s (Click here to read more about this).
• Researchers report non-invasive (transcutaneous auricular) vagus nerve stimulation may boost the drive to work for rewards, offering potential opportunities to treat motivational deficiencies (Click here to read more about this).
• A double blind, sham-controlled study finds repetitive transcranial magnetic stimulation improves Parkinson’s freezing of gait via normalizing brain connectivity (Click here to read more about this).
• New bioRxiv manuscript presents “Action Imagery & Observation in Neurorehabilitation for Parkinson’s Disease” (ACTION-PD), a pilot study of a user-informed home training intervention to improve everyday functional actions (Click here to read more about this).
• Remote administration of the MDS-UPDRS (Parkinson’s assessment) in the time of COVID-19 & beyond (Click here to read more about this).
• Chinese cohort study (n=662 individuals with early‐onset Parkinson’s) provides a better understanding of the clinical & genetic correlations of α‐synuclein, LRRK2, & GBA. 60 rare variants (23 novel) were identified in 73 patients (Click here to read more about this).
  
• Researchers provide Class II evidence that in people with Parkinson’s, concentrations of neurofilament light chain protein in cerebrospinal fluid are associated with more severe disease & worse prognosis (across 2 cohorts; n=99 & 194 – click here to read more about this).
• “Childbirth and delayed Parkinson’s onset: A reproducible nonbiological artifact of societal change” (Click here to read more about this).
  
• Could tinnitus (the perception of noise/ringing in the ears) be a soft indicator of neurodegeneration? Analysis of Taiwan nationwide health insurance database indicates a weak association between tinnitus & higher risk of developing Parkinson’s & Alzheimer’s (Click here to read more about this).

• New bioRxiv manuscript suggests that transcriptomic mitochondrial alterations are detectable in Parkinson’s monocytes & distinct from microglia (Click here to read more about this).
• Researchers report deep convolutional neural networks identify digital biomarkers for self-reported Parkinson’s. Making way for future population-level screening? (Click here to read more about this).
• Researchers report a representation learning model based on word embeddings, convolutional neural networks, & autoencoders; generates patient representations that lead to meaningful clinical insights (including Parkinson’s – click here to read more about this).
• Detection of Parkinson’s from a 20-step walking test using inertial sensors of a smartphone (Click here to read more about this).
• Rapid & dramatic glucose‐lowering effect of Parkinson’s-associated treatment bromocriptine in an inadequately controlled type 2 diabetes patient with prolactinoma (Click here to read more about this).
• Researchers report that kynurenine pathway metabolite levels are altered in both the periphery & the CNS in a Parkinson’s cohort (n=100), & these changes are associated with symptom severity. Novel biomarkers? (Click here to read more about this).
• Researchers report highly expressed KIR3DL1 variants protect against more debilitating symptoms of Parkinson’s, strongly implying a role for natural killer cells in PD progression & manifestation (n=1314 PD patients & 1978 controls – click here to read more about this).
  
• Researchers demonstrate similar patterns of local & long-range synchrony of both the nucleus basalis of Meynert & globus pallidus in Lewy body dementia & Parkinson’s dementia (Click here to read more about this).
• Is IQ a new risk factor for PD? Researchers analysed the Swedish Military Service Conscription Registry (1.3M males betwn 1968–1993 ). 1,724 went on to develop Parkinson’s. Early adulthood high IQ score was associated with PD (p < 0.0001 – click here to read more about this and click here to read a SoPD post on this topic).

• Researchers lead a consortium investigating frequency of GBA mutations in Parkinson’s cohort in Ireland (n=314). 8.3% had a GBA variant (vs 3.1% in controls). Curiously, LRRK2 mutations were rare (n=1 – click here to read more about this).
• “Caregiver strain in Parkinson’s spans geopolitical and cultural boundaries & correlates with disease severity” Study from Singapore reports need for better early recognition, education, & support for caregivers of people living with PD (Click here to read more about this).
  
• Researchers analyzed 1700 Parkinson’s cases (842 familial & 858 sporadic) & report clinical features of PD in homo-, heterozygous & digenic variants of PINK1 in Japan (Click here to read more about this).
  
• New report finds Parkinson’s is associated with plasma lipid metabolic disturbance, including an activated sphingolipid metabolism & decreased apolipoproteins. Small study, but interesting (Click here to read more about this).
• A nationwide nested case-control study from Taiwan finds depression in Parkinson’s is significantly associated with anxiety disorders & sleep disturbances. Integrated care involving early detection & treatment is crucial in newly diagnosed (Click here to read more about this).
• Researchers report novel clinicopathological characteristics that may differentiate dementia with Lewy bodies from Parkinson’s dementia (Click here to read more about this).
  
• Remote & unobtrusive screening of subtle fine-motor impairment (using natural smartphone usage) may assist in consolidating early & accurate diagnosis of Parkinson’s (Click here to read more about this).

• “Much greater heterogeneity in the comorbidity & relative impact of individual brain pathologies affecting progressive parkinsonism than previously recognized & this may account in part for its phenotypic heterogeneity in older adults”. The data comes from 1089 decedents who underwent annual clinical testing & autopsy. Implications for Parkinson’s here? (Click here to read more about this).
• Dietary nicotine intake & risk of Parkinson’s: a prospective study of 2 large cohorts (n = 31,615 & 19,523) finds women with greater dietary nicotine intake had a lower risk of PD than those with lower intake (Click here to read more about this).

New clinical trials

• New clinical trial registered: Photopharmics has register the ‘LIGHT-PD’ study – their 6 month double blind, randomized controlled trial (virtual clinic visits at week 0, 13 & 26) of the Celeste Specialized Phototherapy Device in 200 people with Parkinson’s (Click here to read more about this).

• New clinical training study registered: Exploring the feasibility & benefits of digital services during the COVID19 pandemic (“AnhandCOV19”). 1230 participants to be recruited (Click here to read more about this).
  
• New clinical trial registered (& completed): researchers were investigating a probiotics-prebiotic fiber therapy in 48 people with Parkinson’s suffering from constipation (Click here to read more about this).
• New clinical trial registered: researchers will be conducting a Phase II, randomised, cross-over, 6 month study of N-acetyl-cysteine (NAC) in 50 people with Parkinson’s. Brain imaging is primary endpoint (FDOPA PET – click here to read more about this).
• New clinical trial registered: Sage Therapeutics will evaluate the safety/tolerability of SAGE-718 (oxysterol-based PAM of NMDA receptors) & its effects on cog., neuropsychiatric, & motor symptoms in participants with Parkinson’s + mild cognitive impairment (Click here to read more about this).

• New clinical study registered: Mindfulness-based cognitive therapy for people with Parkinson’s & care partners (MBCT-PD-2). Recruiting 48 people for 8-week long MBCT groups to be held btwn Sept 2020 – May 2021 at UCSF (Click here to read more about this).
  
• New clinical trial registered: A multidisciplinary Phase II study of a D-amino Acid Oxidase Inhibitor (DAAOI) in 60 people with Parkinson’s with dementia has started in Taiwan (Click here to read more about this).
• New clinical study registered: The differential diagnosis & prognosis of idiopathic & atypical Parkinson’s  (by using diffusion MRI) has been registered in Taiwan. Seeking to recruit 288 participants (Click here to read more about this).
  
• New clinical study registered: the Michael J Fox Foundation-backed Parkinson’s Progression Marker Initiative 2.0 (PPMI 2.0) has been registered. This will be a longitudinal, observational, multi-center natural history study to assess progression of clinical features, digital outcomes, & imaging, biologic and genetic markers in 4500 people with Parkinson’s (Click here to read more about this).
  

• New clinical pilot study registered: Researchers the University of Florida will be exploring the effects of Ketone Esters in 10 individuals with Parkinson’s (Click here to read more about this).
• New clinical study registered: the Neurodegenerative Diseases Registry (NDD Registry) in Hong Kong has been set up to build a large database of cognitive, behavioral, lifestyle & psychological data on participants suffering from Parkinson’s, multiple system atrophy (MSA), and progressive supranuclear palsy (PSP – click here to read more about this).
• New clinical trial registered: Enterin Inc has registered a Phase 2b follow-on unblinded, single-arm, safety “Roll-over” study for their ongoing evaluation of ENT-01 in improving constipation & neurologic symptoms in Parkinson’s (Click here to read more about this).

• New clinical trial registered: Scion NeuroStim ltd are initiating a double-blinded, placebo-controlled, randomized clinical trial designed to evaluate their caloric vestibular neuromodulation device on 20 people with Parkinson’s (Click here to read more about this).
• New clinical trial registered: A pilot, randomised, placebo-controlled trial investigating tocotrienols (members of the vitamin E family) in 100 individuals with Parkinson’s for 104 weeks in Singapore (Click here to read more about this).
  

 

Clinical trial news

• Researchers at Biogen present Phase II dose selection for their Parkinson’s-targeted alpha synuclein–targeting antibody Cinpanemab (BIIB054) based on target protein binding levels in the brain (Click here to read more about this).

• Evidence from a small Alzheimer’s SPECT imaging study, suggests Parkinson’s therapy Rasagiline (in conjunction with acetylcholinesterase inhibitors) has beneficial effects on brain perfusion (increased regional cerebral flow – click here to read more about this).
• INmune Bio announced interim Phase Ib trail data demonstrating that XPro1595 (a soluble TNF inhibitor) decreased neuroinflammation in Alzheimer’s by up to 40% in some regions. Over the 12-week study, whole brain inflammation increased by 5.1% in the untreated group compared to an increase of 1.7% & a decrease of 2.3% in patients treated weekly with 0.3mg/kg or 1.0mg/kg of XPro1595, respectively (Click here to read more about this).
• Anavex Life Science announced that they have enrolled the 1st participant in their Phase 1 study of ANAVEX®3-71 (AF710B) – 2nd gen. sigma-1 & M1 muscarinic receptor agonist targetted at Parkinson’s & Alzheimer’s (Click here to read more about this).

• No clinical benefit found in a Phase IIa clinical trial investigating cell transplantation in Huntington disease. Result may be related to graft rejection. Ectopia & high track number negatively influence the graft outcome (Click here to read more about this).
  
• The plan for a randomized double-blind placebo-controlled multi-center trial to evaluate the efficacy & safety of a Chinese herbal formula (Bushen Yisui & Ziyin Jiangzhuo) for constipation in Parkinson’s has been published (Click here to read more about this).
• Pharmaceutical company Pfizer obviously likes what it is seeing in UK biotech firm Mission Therapeutics, which is developing deubiquitylating enzyme (DUB) inhibitors for indications like Parkinson’s (Click here to read more about this and click here to read an old SoPD post on DUB inhibitors).

• Annovis Bio announces that they have received institutional review board approval to initiate a 15 site, 4 week, Phase II clinical study of ANVS401 (Posiphen) in 68 people with Parkinson’s or Alzheimer’s. Results Q1 2021. (Click here to read more about this).
• The results of a randomised controlled trial evaluating the effects of intensive speech treatment on intelligibility in Parkinson’s have been published (Click here to read more about this).
• IPO documents for Inhibikase Therapeutics suggest the company has filed 2 INDs for cABL inhibitor IkT-148009, one for Parkinson’s & one for the treatment of PD-related gastrointestinal complications; 1st dosing of PD patients shortly after the conclusion of the offering (Click here to read more about this).

• Researchers report no significant differences related to age or daily drug dose in tolerability, safety or efficacy of the Parkinson’s treatment Safinamide (MAO-B inhibitor) – a retrospective study (Click here to read more about this).
• A randomized, double-blind, controlled trial of 38 healthy adults suggests hydrogen-rich water increases antioxidant capacity; reducing inflammatory responses. Implications for Parkinson’s? (Click here to read more about this).
• PTC Therapeutics announced that the first subject in the Phase 1 clinical trial evaluating PTC857 in healthy volunteers has been dosed. PTC857 (previously EPI 857) is a small molecule inhibitor of 15-Lipoxygenase for conditions like Parkinson’s (Click here to read more about this).

Other news

• LYSOGENE and the Weizmann Institute of Science are partnering to develop a novel adeno-associated virus (AAV) gene therapy approach for neuronopathic Gaucher disease, Parkinson’s, & other conditions associated with mutations of the GBA1 gene (Click here to read more about this).
• Tranquis Therapeutics has launched with $30M in series A funding to explore myeloid immune cell dysfunction in neurodegenerative conditions, like ALS, FTD & Parkinson’s. Lead candidate, TQS-168, goes to the clinic in 2021 (Click here to read more about this).

• How do you conduct an ‘at home’, telemedicine, Phase 3 clinical trial for Parkinson’s? Photopharmics and University of Rochester Medical Center are collaborating to do just that with their “Celeste Light for PD” Trial (a 6 month study of Celeste®, a specialized light therapy device – click here to read more about this).
• Danish biotect firm Orphazyme A/S – who are currently clinically testing heat shock protein co-activator arimoclomol – announced that it is joining the Michael J Fox Foundation Parkinson’s Disease Research Tools Consortium (Click here to read more about this).

• AC Immune reports new data for its next generation alpha-synuclein PET tracer. Preclinical results demonstrate enhanced contrast & alpha-synuclein target specificity (Click here to read more about this).

 

Review articles/videos

And there it is, just some of the highlights from July 2020 – 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 August!!!

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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.

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