Monthly research review – October 2019

 

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 October 2019.

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

 


So, what happened during October 2019?

In world news:

October 1st – It was reported that human embryos have extra hand muscles, which are also found in lizards. But these muscles are lost in most human adults (curiously 14% of us retain them, with no side effects – click here and here to read more about this).

October 7th – The 2019 Nobel prize for medicine was awarded jointly to William G. Kaelin Jr, Sir Peter J. Ratcliffe and Gregg L. Semenza “for their discoveries of how cells sense and adapt to oxygen availability” (Click here to read more about this).

October 12th – Typhoon Hagibis made landfall in Japan. It was the biggest storm to hit the region in decades

October 23rd – The technology company Google laid claim to quantum supremacy.

October 28th – It was discovered that the solar system may have a new smallest dwarf planet, named Hygiea

October 31st – A fire destroyed the majority of the 500-year-old Japanese Shuri Castle, a UNESCO World Heritage Site

 

And it was with sadness that we learnt at the SoPD of the passing of Professor Ken Bowler. Here is the UK, Ken was influential in establishing the Parkinson’s UK Research Support Network, and he helped to make the Edinburgh Research Interest Group into the amazing group that it is. He will be greatly missed (Click here to read more about Ken).

Prof Ken Bowler (right) with Dr Tilo Kunath in Edinbugh this year

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

In October 2019, there were 834 research articles added to the Pubmed website with the tag word “Parkinson’s” attached (6788for all of 2019 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. A new GCase activator:

Researchers in Chicago reported a new small-molecule modulator of glucocerebrosidase (GCase) called S-181 which improves pathogenic phenotypes in human dopaminergic neuronal models & transgenic GBA mouse models of Parkinson’s. S-181 increased WT GCase activity in iPSC-derived dopaminergic neurons from sporadic PD, as well as carriers of GBA1, LRRK2, DJ-1, & PARKIN variants. S-181 treatment of these PD cells partially restored lysosomal function, lowered oxidized dopamine, glucosylceramide & α-syn. A new company Surmount Bio has been set up to explore & develop S-181 further. ( to read more about this and click here to read the press release).

2. Farnesyltransferase inhibition for Parkinson’s?

Other researchers in Chicago reported that stress-induced cellular clearance of waste in cells is mediated by the SNARE Protein ykt6, which is inhibited by Parkinson’s-associated α-synuclein (leading to disruption of the lysosomal stress response). Farnesyltransferase inhibitors restores activity and protect cells ( to read more about this and click here to read a SoPD post on the topic)

3. Further insights into LRRK2 inhibition

Researchers reported that a brain-penetrant LRRK2 kinase inhibitor (PF-360) improved endosomal maturation & lysosomal function, but also prevented rotenone-induced neurodegeneration in Parkinson’s models ( to read more about this). LRRK2 inhibition is currently being clinically tested in Parkinson’s (Click here to read an old SoPD post on this topic).

4. Putting the brakes on LRRK2

More on LRRK2: Researchers in Dundee (Scotland) and Stanford (USA) reported that PPM1H acts as a key modulator of Parkinson’s-associated LRRK2 signaling. They provide compelling evidence that PPM1H acts to dephosphorylate Rab proteins, which counteracts LRRK2 signalling. “Targeting PPM1H to increase its activity or expression in order to promote Rab protein dephosphorylation could be explored as a therapeutic strategy for preventing &/or treating LRRK2-mediated Parkinson’s” ( to read more about this and click here to read the press release).

5. And yet more on LRRK2: Early detection

Data from the Michael J Fox Foundation supported PPMI project found evidence of subtle motor & non-motor signs of Parkinson’s in non-manifesting carriers of LRRK2 genetic variants (compared with healthy controls) that can precede DAT deficit. Longitudinal data now essential to confirm these findings ( to read more about this).

5. Lots of Parkinson’s research funding opportunities

The Aligning Science Across Parkinson’s (ASAP) initiative in partnership with Michael J Fox Foundation seeks to support multi-disciplinary/-institutional research teams to address key knowledge gaps regarding Parkinson’s (Click here to read more about this and click here to read an SoPD post on this topic).

The Chan Zuckerberg Initiative also launched a new funding opportunity for innovative approaches to fighting neurodegenerative conditions like Parkinson’s (Click here to read more about this).

 

Basic biology news

  • Parkinson’s-associated PINK1 & Parkin genetically interact with cell cycle-regulatory proteins. PINK1/Parkin-mediated activation of Tank Binding Kinase 1 (TBK1) causes its sequestration at damaged mitochondria, blocking TBK1’s participation in cell cycle ( to read more about this).
  • Researchers report that Glutathione transferase omega 1-1 (GSTO1-1) is involved in NLRP3 inflammasome activation. They find C1-27, an inhibitor of GSTO1-1, protects inflammatory mouse model. Implications for Parkinson’s here? ( to read more about this).
  • Researchers report that lifespan-increasing drug nordihydroguaiaretic acid (NDGA) inhibits p300 & activates autophagy. Curious molecule NDGA – has been reported to delay onset in Parkinson’s flies ( to read this report and click here to read more about the Parkinson’s fly research).

  • Mutations in the retromer VPS35 are associated with Parkinson’s. Now researchers have a manuscript on bioRxiv suggesting that with aging, retromer insufficiency triggers progressive endolysosomal dysfunction & lysosomal stress ( to read more about this).
  • New report suggests botulinum toxin A (botox) injections into the entopeduncular nucleus improved dynamic locomotory parameters in a rodent model of Parkinson’s ( to read more about this).
  • Researchers demonstrate that chronic corticosterone aggravates behavioral & neuronal symptomatology in a mouse model of Parkinson’s-associated alpha-synuclein pathology ( to read more about this).
  • A multi cohort analysis of blood, characterizing >1000 proteins in >500 people indentified potential biomarkers for Parkinson’s ( to read more about this).
  • Salidroside – a bioactive component extracted from Rhodiola rosea L. – protects dopamine neurons by enhancing Parkinson’s-associated PINK1/Parkin-mediated mitophagy ( to read more about this and click here for an interesting review on Salidroside).
  • Researchers report activation of necroptosis in postmortem brain tissue from people with Parkinson’s & also in a toxin-based mouse model of the condition. Pharmacological inhibition of RIPK1 in PD models reduced cell loss & motor issues ( to read more about this).
  • Researchers have a manuscript on bioRxiv suggesting that Parkinson’s-associated α-synuclein noncovalent dimers are abundant in micromolar concentration & compact; in equilibrium with monomers ( to read more about this).
  • A combination of phenolic compounds from olive oil (including oleuropein, p-coumaric acid & tyrosol) reported to improve neuronal survival in cell models of Parkinson’s ( to read more about this).

  • Protein silencing research for Parkinson’s gets a powerful new tool! You have heard of PROTAC? Well now there’s AUTAC – AUtophagy-TArgeting Chimera. Mito-AUTAC enhances mitochondria quality via the rapid removal of fragmented mitochondria ( to read more about this).
  • Researchers investigate alpha-synuclein aggregation & reveal features of an early onset mutation in Parkinson’s. They provide a framework for studying the early stages of amyloid conversion ( to read more about this).
  • New research suggests Parkinson’s-associated PINK1 & Parkin are required for the redistribution of Mitochondrial E3 ubiquitin ligase (MITOL)/March5 to peroxisomes, providing new instights regarding ubiquitylation of damaged mitochondrial proteins ( to read more about this).
  • Researchers asked whether the cGAS/STING pathway plays a role in Parkinson’s-associated PINK1/Parkin related pathology in flies. The answer: Loss of Sting (or effector Relish) was not sufficient to suppress behavioral & mitochondria issues in the flies. The results in this bioRxiv  manuscript contrast with previous mouse work, & may suggest species/evolutionary differences. ( to read more about this and click here to read the previous research).
  • New data suggests Ten-eleven translocation 2 (TET2) may drive proinflammatory activation of microglia & induction of metabolic reprogramming upon inflammatory stimulus. Potential drug target to control exacerbated neuroinflammatory response in Parkinson’s? ( to read more about this).
  • New research demonstrates that small molecules efficiently reprogram human fibroblasts into glutamatergic neurons. Proneurogenic & neuroprotective agent P7C3-A20 seems to be the key in this cocktail. Potential for Parkinson’s cell replacement therapy? ( to read more about this).
  • Researchers report that Longevity Biotech’s synthetic Vasoactive Intestinal Peptide receptor-2 agonist (LBT-3627) induces regulatory T-Cell neuroprotective activities in models of Parkinson’s ( to read more about this).

  • Researchers report dichloroacetate-induced activation of metabolic flux in the mitochondrion may be a mechanism to restore normal mitochondrial fusion-fission dynamics in metabolically challenged cells. Implications for Parkinson’s? ( to read more about this).
  • By tuning the charge of Parkinson’s-associated alpha synuclein dimers, researchers enhanced their binding affinity & identified a construct that inhibits fibril elongation at nanomolar concentration (IC50≈20 nM – to read more abiut this).
  • Researchers report data suggesting that Parkinson’s-associated LRRK2 associates with & dissociates from distinct membrane compartments to phosphorylate Rab substrates; LRRK2 can modify misdelivered Rab substrates ( to read more about this).
  • Monomeric alpha synuclein can suppress amyloidogenesis of prion protein in vitro? Thioflavin-T assays & transmission electron miscopy sugget that monomeric α-syn inhibits the nucleation step of amyloidogenesis without inhibiting the growing step (Click here to read more about this).
  • Scientists report impaired macroautophagy paradoxically ENHANCES dopamine transmission, improving movement while worsening pathology. Could changes to dopamine synaptic function conceal Parkinson’s? ( to read more about this).
  • 2-DPAN: A useful new tool for monitoring the dynamic changes of Lipid droplets in Parkinson’s. Curious finding: Oleic acid increased the number of lipid droplets, which provided a protective effect for cells from the neurotoxin 6-OHDA ( to read more about this).
  • Researchers report that 7S DNA accumulation, low mtDNA replication, high H-strand transcription, & low mtDNA release compose a pattern of mtDNA dysfunction shared by both idiopathic Parkinson’s & LRRK2-PD fibroblasts ( to read more about this).

  • Researchers report that the influence of GBA enzyme replacement on Parkinson’s-associated α-synuclein is mediated through cathepsin D. If you remove cathepsin D, GCase replacement fails to reduce monomeric α-synuclein levels in GBA1 mutant neurons ( to read more about this).
  • A BioRxiv manuscript suggests cellular ATP homeostasis ensures proteostasis. ATP-reduced yeast mutants exhibit higher levels of Parkinson’s-associated alpha synuclein aggregation. Pharmacological elevations in ATP levels prevented α-syn accumulation. The researchers found that some intrinsic proteins & aggregation-prone model proteins (including α-syn) aggregated & were cytotoxic in ALL of their ATP-reduced mutants that they tested. Even in transcient ATP reductions ( to read more about this).
  • Researchers use DREADDs technology to modulate neuronal activity & assess the effect in an α-SYN-based model of Parkinson’s. They report chronic nigral neuromodulation aggravates behavioral deficits & synaptic changes in the model ( to readmore about this).
  • Nei-like 1 inhibition results in motor dysfunction & promotes inflammation in mouse neurotoxin models of Parkinson’s (Click here to read more about this).
  • Researchers report that highly conserved & disordered protein SERF exhibits a high degree of plasticity & forms fuzzy, highly extended complexes with amyloid-prone proteins (including Parkinson’s-associated alpha synculein – click here to read more about this).
  • Researchers propose PP2A & S6 kinase as modifiers of Parkinson’s-associated Leucine-Rich Repeat Kinase (LRRK2) -Induced neurotoxicity (in flies? – to read more about this).
  • Researchers report a bacterial platform that enables the biosynthesis of molecular libraries with expanded diversities & their direct functional screening for discovering protein aggregation inhibitors. They generated a combinatorial library of ~200 million drug-like, cyclic peptides & rapidly screened it for aggregation inhibitors against the beta amyloid peptide (Aβ42), which is linked to Alzheimer’s. Potential here for an alpha synuclein/Parkinson’s screen ( to read more about this).

  • Researchers provide a mechanism by which partially oxidized DJ-1 counteracts Parkinson’s -associated α-synuclein aggregation at initial stages of aggregation & provide evidence of a deleterious effect of remodeled α-synuclein species ( to read more about this).
  • Researchers describe an alternative approach to profiling xenografts. Utilizing differences in the RNA sequence between species, they demonstrated profiling of the complete transcriptome & an unbiased characterization of graft composition ( to read more about this).

 

Disease mechanism

  • New study reports that Rho-associated coiled-coil protein kinase 1 (ROCK1) is activated in neurotoxin Parkinson’s cell model & ROCK1 inhibitor Y-27632 blocks aberrant mitochondrial fission in dying dopamine neurons ( by suppressing Drp1 – to read more about this).
  • Researchers have a manuscript on bioRxiv suggesting that ATF4 regulates neuronal death in models of Parkinson’s. They also show that eIF2α kinase inhibitor C16 suppresses MPP+ & 6-OHDA induced ATF4 activation ( to read more about this).
  • Researchers have a manuscript on bioRxiv presenting the 1st genome-wide study of histone acetylation in Parkinson’s. Strong evidence that H3K27 acetylation is decoupled from gene expression in PD ( to read more about this).
  • Researchers have a manuscript on bioRxiv suggesting that striatal Nurr1 levels facilitates the dyskinetic state & exacerbates L-dopa-induced dyskinesia in rodent models of Parkinson’s (even LID-resistant Lewis rats! to read more about this).

  • Researchers report HDAC5 & HDAC9 as novel regulators of BMP-Smad signaling, that may additionally be therapeutic targets worthy of further exploration in models of Parkinson’s ( to read more about this).
  • Further preclinical data suggesting that developing midbrain α‐synuclein pathology in a Parkinson’s rodent model is associated with alterations in the enteric nervous system & the gut microbiome (Click here to read more about this).
  • α-synuclein preformed fibrils induce a synucleinopathy in non-human primates with authentic Lewy pathology & nigrostriatal changes indicative of early Parkinson’s” (Click here to read more about this).
  • Non-ferritin-bound iron is sufficient per se to cause both cell senescence & ferroptotic cell death in human fibroblasts & neurons. New study provides strong evidence supporting the primary role of iron in neuronal aging & degeneration (like Parkinson’s –  to read more about this).
  • Researchers report that mitochondrial dysfunction induced by Parkinson’s-associated CHCHD2 T61I genetic mutation promotes α-synuclein aggregation. They used brain autopsy, induced pluripotent stem cells (iPSCs), & fly genetics to show this (Click here to read more about this).
  • Researchers report positive effect of an electrolyzed reduced water (ERW) on gut permeability, fecal microbiota & liver in a permethrin (PERM) pesticide model of Parkinson’s ( to read more about this).
  • Researchers report that viral overexpression in rodents of the C-terminal part of Parkinson’s-associated LRRK2 containing the mutant G2019S kinase domain is sufficient to trigger the degeneration of dopamine neurons (via cell-autonomous mechanisms – click here to read more about this).

  • Parkinson’s is not a monogenetic condition. Researchers & collaborators have identified serine racemase (SSR) as a novel patient-specific, developmental, genetic modifier involved in aberrant phenotypes. SRR product (d-serine) rescues patient phenotypes ( to read more about this).
  • Researchers report that Parkinson’s-associated LRRK2 plays an essential role in maintaining nuclear envelope integrity, suggests a novel phosphorylation-independent loss of function mechanism that may synergize with other neurotoxic effects ( to read more about this).
  • Researchers further define the pattern of propagation of Parkinson’s-associated alpha-synuclein inclusions & develop a mathematical model based on the known mouse brain connectome. “The pattern of propagation we observed in vivo is consistent with axonal transport of alpha-synuclein aggregate seeds, followed by transsynaptic transmission. By contrast, simple diffusion of alpha-synuclein fits very poorly our in vivo data” ( to read more about this).
  • Researchers provide in vivo evidence suggesting that the IRE1 pathway drives Parkinson’s progression through coupling ER stress to autophagy-dependent neuron death ( to read more about this).
  • Researchers & collaborators have a manuscript on BioRxiv suggesting a novel mechanism for PINK1 pathogenicity in Parkinson’s, & show that low doses of the cholesterol depleting drug β-cyclodextrin reverse PINK1-specific phenotypes ( to read more about this).
  • “Initiation of Parkinson’s from gut to brain by δ-secretase” – apparently δ-secretase cleaves both α-Syn & Tau, & mediates their fibrillization & retrograde propagation from the gut to the brain (Click here to read more about this).
  • Further evidence that structurally distinct α‐synuclein fibrils induce robust Parkinson’s pathology – in this case G51D α‐syn fibrils have higher β‐sheet contents & more widespread pathology in model of PD (Click here to read more about this).

  • Researchers have a bioRxiv manuscript suggesting that Parkinson’s phenotypes in patient specific brain organoids are improved by 2-Hydroxypropyl-β-Cyclodextrin treatment (which has been clinically tested for Niemann Pick Type C – to read more about this).
  • Researchers have a bioRxiv manuscript further establishes the relevance of pRab10 as a prognostic Parkinson’s marker & a powerful tool for determining LRRK2 inhibitor efficacy; also for stratifying PD patients for LRRK2 inhibitor treatment ( to read more about this).
  • Researchers have a manuscript on bioRxiv suggesting that in primates a small amount of singular α-syn aggregates from postmortem human Parkinson’s brain is as toxic as larger amyloid fibrils present in the Lewy Bodies ( to read more about this).

 

Clinical research

  • Researchers report an exploratory investigation of non-motor feature assessment using a wrist-worn wearable sensor in 108 people with Parkinson’s ( to read more about this).
  • Researchers report the results of a randomized crossover comparison of short vs conventional pulse‐width deep brain stimulation on stimulation‐induced dysarthria in Parkinson’s (Click here to read more about this).
  • Researchers suggests monocytic changes in the blood of people with Parkinson’s. These cells show reduced viability & are unresponsive to specific stimuli, which might have a relevant consequence for disease progression (Click here to read more about this and click here for the press release).

  • Interesting report trying to estimate prodromal marker progression in idiopathic rapid eye movement sleep behavior disorder patients with prodromal Parkinson’s in order to calculate sample size for future neuroprotective trials (Click here to read more about this).
  • Researchers have a manuscript on bioRxiv suggesting no genetic evidence for involvement of alcohol dehydrogenase genes in risk for Parkinson’s, based on 15,097 PD cases & 17,337 healthy controls ( to read more about this).
  • New twice-weekly 12-week yoga intervention study suggests yoga improves balance & lower-back pain – but not anxiety – in people with Parkinson’s ( to read more about this).
  • Researchers present data suggesting aerobic exercise in people with Parkinson’s alters the responsivity of the ventral striatum (related mesolimbic dopaminergic pathway changes) & increases evoked dopamine release in the caudate nucleus (Click here to read more about this).
  • Researchers report that the recently developed “Parkinson’s Disease Composite Scale” is adequately responsive to acute Levodopa challenges ( to read more about this).
  • Long term follow-up of excessive daytime sleepiness (EDS) in Parkinson’s found that EDS remained stable over 10 years & did not deteriorate in parallel with worsening of motor symptoms ( to read more about this).
  • The epigenetics of Parkinson’s – researchers have a manuscript on bioRxiv suggesting that long disease course in Parkinson’s is associated with greater hemispheric asymmetry in neuronal epigenomes than a short course. DNA methylation in neurons isolated from either the left or right prefrontal cortex of 57 PD patients & 48 controls. “During aging, healthy neurons show a progressive loss of hemispheric asymmetry in the epigenome, which is amplified in PD” ( to read more about this).
  • Lifetime coffee intake of ≥2 cups/day has been found to be significantly associated with a lower Alzheimer’s-associated β-amyloid positivity (PET imaging) compared to coffee intake of <2 cups/day, even after controlling for potential confounders ( to read more about this).

  • Researchers suggest a genetic association between Midnolin (MIDN) & Parkinson’s in a British population cohort, using the WTCCC2 cohort data (2860 controls & 2168 PD) – supporting previous data from Japanese cohort ( to read more about this and click here for the previous research).
  • Researchers provide an interesting report on falling in Parkinson’s. In a study of 404 PD patients seen in 1 year, 65 (16%) fell more than once. 28 fell mainly while walking & 26 fell mainly while standing (Click here to read more about this).
  • Researchers report that people with Parkinson’s & impulsive compulsive behaviours have lower α-synuclein protein load & dopamine D3 receptor levels in the nucleus accumbens region of the brain (Click here to read more about this).
  • Researchers highlight key conceptual developments in the generation of functional genomic annotations & tools that integrate these annotations with GWAS results, & discuss the opportunities & challenges associated with them ( to read more about this).
  • Researchers report that dopaminergic medication reduces striatal sensitivity to negative outcomes in Parkinson’s, further elucidating the role of dopamine-driven learning differences in PD ( to read more about this).
  • Korean researchers publish a report suggesting that long term treatment with high-dose ambroxol in 4 patients with Gaucher disease & myoclonic epilepsy, is safe & “might help to arrest the progression of the neurological manifestations in Gaucher disease”. This is relevant to Parkinson’s as the results of a Phase II clinical trial of ambroxol in PD should be published soon (Click here to read more about the Gaucher results).

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  • New research suggests higher urine bis(monoacylglycerol)phosphate levels in LRRK2 G2019S mutation carriers: Implications for therapeutic development ( to read more about this).
  • Intriguing report demonstrating marked heterogeneity in the anatomical distribution of neurotransmitter markers in the human striatum. Age‐dependent loss of dopamine did not correspond to the loss described for Parkinson’s, indicating different mechanisms (Click here to read more about this).
  • Small study, but Polish researchers report elevated fecal calprotectin levels in 43% of participants with Parkinson’s compared to 0% of controls subjects. A marker of the gut immune system activation? ( to read more about this).
  • Researchers report distinct autoimmune anti-α-synuclein antibody patterns between Multiple System Atrophy (MSA) & Parkinson’s (suggesting distinct autoimmune-involving mechanism responses toward α-syn – to read more about this).
  • Chinese researchers report iron concentration does not differ in blood but tends to decrease in cerebrospinal fluid in Parkinson’s. Small study, but also involves meta analysis of previous literature ( to read more about this).
  • Saccades may be a neurophysiological biomarker for Parkinson’s. But researchers report that prosaccadic latency is significantly affected by dopaminergic medication, which may complicate its use as a biomarker in drug trials (Click here to read more about this).
  • Annual disease progression rates over 5 years exhibited by a cohort of 55 exercisers with Parkinson’s (60 minutes+ of exercise/week) were lower than those previously reported for motor decline in general samples with PD ( to read more about this).

  • Associations with metabolites in 1,954 individuals of Chinese origin suggest new metabolic roles in Alzheimer’s & Parkinson’s – highlight the role of metabolites as intermediate modulators in disease metabolic pathways (Click here to read more about this).
  • Researchers assessed DNA from 7849 Spanish individuals & found that PARK2 (Parkin) as a major hallmark of Parkinson’s etiology in Spain. Also how leveraging unique & diverse population histories can benefit genetic studies ( to read more about this).
  • New insights into cortico-basal-cerebellar connectome: clinical & physiological considerations. Important implications for Parkinson’s (Click here to read more about this).
  • “We found larger volumes of the whole brainstem, midbrain, and medulla oblongata in the individuals with Parkinson’s” Interesting manuscript on BioRxiv on the genetic architecture of human brainstem structures ( to read more about this).
  • An exploratory meta-analysis of 5 retrospective observational cohort studies, found that thiazolidinediones therapy use was associated with reduced risk of Parkinson’s in diabetic patients ( to read more about this).
  • Resarchers have a manuscript on bioRxiv with data that supports the feasibility of levodopa phMRI hysteresis mapping to measure the severity of dopamine denervation objectively & simultaneously in several brain regions for staging Parkinson’s ( to read more about this).
  • Researchers propose a quick test of cognitive speed that may help to predict the development of dementia in Parkinson’s ( to read more about this).
  • A retrospective epidemiologic analysis found mortality from neurodegenerative disease (such as Parkinson’s) was higher & mortality from other common diseases lower among former Scottish professional soccer players (then among matched controls – click here to read more about this).

  • Researchers reports genetic, structural AND functional evidence linking TMEM175 to synucleinopathies. Interesting that TMEM175 p.M393T found to be associated with reduced GCase activity (Click here to read more about this).
  • Transportation innovation to aid Parkinson’s clinical trial recruitment – a pilot project to assess feasibility of a third-party ride sharing service & to explore the possibility that reducing the transportation burden may enhance participation in studies (Click here to read more about this).
  • Researchers demonstrate worse motor function & more prevalent orthostasis in REM Sleep Behaviour disorder subgroup with abnormal compared to normal DAT-SPECT. DAT binding is also associated with olfactory dysfunction ( to read more about this).
  • Small numbers, but Danish researchers report that there is a trend toward use of non-aspirin NSAIDs & an associated reduced risk of Multiple System Atrophy (MSA). Larger sample sizes & longer exposure periods are needed to confirm (Click here to read more about this).
  • Israeli researchers suggest GBA-E326K genetic variant is more likely to affect Parkinson’s risk when accompanied by another mutation. May have an additive effect on risk & earlier age of onset for carriers of LRRK2/mild-GBA double mutations (Click here to read more about this).
  • Using virtual reality during deep brain stimulation surgery, researchers identified signal changes in the subthalamic nucleus coincident with the onset of freezing episodes in patients with Parkinson’s (Click here to read more about this).

 

New clinical trials

  • A new clinical trial registered: A Phase 1/2a study of the Prevail Therapeutics gene therapy PR001A treatment in people with GBA-associated Parkinson’s (“PROPEL”). This randomized, double-blind, sham procedure-controlled, ascending dose study will recruit 16 subjects (Click here to read more about this and click here to read a previous SoPD post on this topic).

  • New clinical trial registered to analyze the molecular & clinical mechanisms of the relationship between the GBA mutations and Parkinson’s (Click here to read more about this).
  • New clinical trial registered: Abbvie is starting Phase I testing of their Parkinson’s immunotherapy treatment, ABBV-0805 – which is an antibody against alpha-synuclein. Assessing safety, tolerability, pharmacokinetics & immunogenicity in 32 PD subjects (Click here to read more about this).

  • Interesting new clinical trial registered for Parkinson’s… I have no idea what it involves, but “Virtual Reality” & “Antigravity” pulled me in (Click here to read more about this).
  • New clinical study registered: Atlas Biomedical are recruiting 200 people in a case-control study to identify microbiome & genetic differences between healthy controls & people with Parkinson’s (Click here to read more about this).
  • New spinal cord stimulation in Parkinson’s clinical trial kicking off at Imperial College (Click here to read more about this).
  • A new clinical study has been registered with the aim of identifying measures that can detect Parkinson’s & Progressive Supranuclear Palsy (PSP) progression over shorter time periods than is currently possible (Click here to read more about this).
  • A new clinical study has been registered investigating “Symprove” probiotic use in 70 people with Parkinson’s. This 12 week study is a “path finding” study for a larger future full-scale clinical study (Click here to read more about this).

 

Clinical trial news

  • Yumanity Therapeutics announced that the first patient cohort has been dosed in a Phase 1 clinical trial of Yumanity’s lead investigational therapy, YTX-7739, which is being developed as a potential treatment for Parkinson’s (Click here to read more about this and click here for a previous SoPD post on this topic).

  • The researchers coordinating the PD-STAT clinical trialhave published the protocol of the study. This study is a double-blind, placebo-controlled study assessing Simvastatin as a neuroprotective treatment for Parkinson’s ( to read more about this).
  • Recruitment is about to start for the next phase of the Exenatide-PD clinical trial programme to determine in a larger cohort whether this diabetes treatment can slow down disease progression in Parkinson’s (Click here to read more about this).

 

 

  • Parkinson’s UK’s latest Virtual Biotech project is a clinical trial of cannabidiol (CBD) for treating Parkinson’s-related psychosis (Click here to read more about this).
  • Reanalysis of Biogen’s Phase III clinical trial data of their Alzheimer’s immunotherapy treatment (Aducanumab) finds positive results at higher doses (Click here and here to read more about this).

Other news

  • Time matters: a call to prioritize brain health – researchers call for a campaign to promote a ‘brain-healthy lifestyle‘ to reduce the risk of developing neurodegenerative conditions, like Alzheimer’s & Parkinson’s ( to read more about this and click here for the press release).
  • “We are not looking to shut down genes, but to modify RNAs & move them from a diseased state to a normal state through base targeting vs shutting the gene off” – Korros Bio sounds really interesting. And they may be interested in Parkinson’s… ( to read more about this).
  • ND-BioSciences awarded a grant from The Michael J. Fox Foundation to help advance the foundation’s α-Synuclein biomarkers discovery and validation programs ( to read more about this).

  • The Center Without Walls collaboration has received a 5-year $20M grant from the US NINDS to develop a radioactive tracer that will be able to detect Parkinson’s early & provide progression info ( to read more about this).
  • The Parkinson’s Foundation has launched a new national program: “Newly Diagnosed: Building a Better Life with Parkinson’s“. It is a new campaign designed to arm people who are newly diagnosed with the knowledge, tools & resources they need to navigate life with PD ( to read more about this and click here for the press release).

 

  • In October 2018, a diverse stakeholder group convened in Washington DC, to examine how electronic health record, mobile, & wearable technologies could be applied to clinical trials ( to read more about this).
  • A useful guide to what folks with Parkinson’s can do to improve orthostatic hypotension problems ( to read more about this).
  • Acorda Therapeutics has launched a new tool for people with Parkinson’s to improve communication about OFF periods – “Do Tell” Your Doctor Tool (Click here to read more about this and click here to see the website).

  • More artificial intelligence being thrown at Parkinson’s – Israeli startup Mon4t has been granted $75,000 to support research and clinical development of its smartphone application, EncephaLog ( to read more about this).
  • Clene Nanomedicine presented new preclinical neuroprotection data for their compound CNM-Au8 in multiple Parkinson’s models, & the launch of their Phase 2 clinical trial, REPAIR-PD. The REPAIR-PD trial – It is a 31P-MRS brain imaging study to determine how CNM-Au8 changes of CNS metabolism. 24 Parkinson’s participants drink 2oz. (50ml) of the nanocrystal suspension each morning for 12 weeks. Results Q3 2020. ( to read more about this and click here for information regarding the trial).

  • Interesting article discussing the artificial intelligence research BERG & Astra Zeneca are conducting on Parkinson’s. This is a good start: “One of the things I could never understand was why the life science industry seemed to treat all patients the same way & provide all of them with the same drug” (Click here to read more about this).
  • More news about research on training dogs to smell Parkinson’s (Click here to read more about this).

 

Review articles/videos

  • Interesting review about gut inflammation in association with the pathogenesis of Parkinson’s ( to read more about this).
  • Nice report exploring the idea of the “quadruple decision making” model for Parkinson’s: best available scientific evidence, professional expertise, the personal needs + preferences of patients, & big data approaches ( to read more about this).
  • Interesting review of the evidence supporting a possible influential role for the appendix in Parkinson’s; including constructive discussion on the appendectomy research ( to read more about this).

  • An interesting review of the connection between inflammatory bowel disease & Parkinson’s ( to read more about this).
  • A review of faecal transplantation & pro-/prebiotics in Parkinson’s. Is it all a load of hype? ( to read more about this).
  • A review of the links between the microbial composition with the observed alterations of bacterial metabolites & their possible impact on the immune system in Parkinson’s ( to read more about this).
  • A fascinating discussion by researchers from the biotech company Enterin on gastrointestinal immunity & alpha synuclein – how targeting the formation of a-syn aggregates in the enteric nervous system may slow the progression of Parkinson’s ( to read more about this).
  • Researchers discuss the contributions of both intracellular and intercellular mitochondrial dynamics to the etiology of Parkinson’s ( to read more about this).
  • New review discusses the interdependence of lipids and proteinopathy. Are certain neurodegenerative conditions like Parkinson’s simply resulting from disturbed lipid homeostasis over time? ( to read more about this).

  • A useful review on the role of mitochondria & oxidative stress in the Parkinson’s etiology & the potential crosstalk between Nrf2 signaling & mitochondrial function in PD ( to read more about this).
  • Interesting review of opioid‐like neuropeptide nociceptin/orphanin FQ (N/OFQ) and its receptor NOP in the context of PD. Could NOP receptor antagonists provide both symptomatic & disease modifying potential? (Click here to read more about this).
  • Parkinson’s Life has lauched an important new series focused on women & Parkinson’s – exploring the specific ways the condition affects women & pressing for change. Important topic! (#ShesAParkyToo – to read more about this).

 

* * * * * * * * * * * *

And there it is, just some of the highlights from October 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 November!

 


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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