Monthy research review – June 2020

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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 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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So, what happened during June 2020?

In world news:

June 2nd – Researchers reported that animal DNA extracted from parchments helped them piece together the Dead sea scrolls – a fascinating story (Click here to read the resesarch report and Click here to read a summary of the research).

June 6th – US Black Lives Matter protests entered their 12th consecutive day, and countries around the world held their own protests.

June 16th – Researchers report that there may be as many as six billion Earth-like planets in our galaxy (Click here to read more about this).

20th June – The Siberian town of Verkhoyansk broke the record for the highest temperature ever recorded within the Arctic Circle – it hit 38 degrees Celsius (that is 100.4F). The average daily high for the town in June is 19.9 degrees Celsius. Surrounding cities recorded similar temperatures (Click here to read more about this).

June 29th – Scientist reported that an asteroid impact (and not volcanoes) made the Earth uninhabitable for dinosaurs

 

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

In June 2020, there were 743 research articles added to the Pubmed website with the tag word “Parkinson’s” attached (5,308 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. AFFiRiS Phase 1 vaccine results

Austrian biotech firm AFFiRiS published the results of their Phase 1 safety & immunogenicity work of the α-synuclein active immunotherapeutic PD01A in patients with Parkinson’s. The results demonstrate that over multiple years of assessments, the treatment was found to be safe and well tolerated. It also caused the immune system to generate antibodies targetting the aggregated form of alpha synuclein, and the investigators saw a reduction in the levels of this protein. Important to remember that this is an open-label study, but the researchers reported no change in MDS-UPDRS part 3 scores or brain imaging data. The study was not designed to assess clinical efficacy of the immunotherapeutic, which requires further exploration”. A Phase 2 trial is now being prepared. ( to read the report, click here to read a press release, and click here to read a SoPD post of this result).

 

2. PTBP1: One and done

Researchers reversed a mouse model of Parkinson’s using the conversion of astrocytes to dopamine neurons in the brain via reduction in the level of a single protein: the RNA-binding protein PTB (PTBP1) ( to read more about this, click here to read the Nature editorial, and click here for the Alzforum write up – an SoPD post is in production…).

3. Probing the brain’s 24-hour biological clock for risk of neurodegeneration

Circadian rhythm disruption in elderly individuals may represent an important prodromal feature for Parkinson’s. Researchers reported longitudinal (11 yrs follow-up) study of 2930 elderly men without PD at baseline. Risk of incident Parkinson’s increased significantly with decreasing circadian amplitude or robustness. “Participants in the lowest quartile for these measures had approximately 3 times the risk of developing PD compared with those in the highest quartile” (Click here to read more about this and click here to read the press summary)

4. GBA: Wider regulation = wider implications

Genetic risk factors puts you at risk, while the genetic modifiers influence the level of risk. Researchers in New Zealand and Australia explored the role of common genetic variations within the GBA gene & what effect they have on Parkinson’s. They identified common noncoding variants within and outside of the GBA gene that may act as genetic modifiers of GBA levels, and some of these could explain aspects of the variability between individuals with regards to age of symptom onset ( to read more about this and click here to read an SoPD post about this research).

5. PAP-kinson’s

Researchers report that Fyn-dependent regulation of Kv1.3 channels plays a role in augmenting the neuroinflammatory response in Parkinson’s, identifying Kv1.3 as a potential therapeutic target. They find that administration of Kv1.3-specific small-molecule inhibitor “PAP-1” significantly inhibited neurodegeneration & neuroinflammation in multiple animal models of Parkinson’s ( to read more about this).

 

Basic biology news

  • Researchers conducted whole genome GOF CRISPR activation screen to identify genes that rescue glucose restriction-induced cell death. They report defective NADPH production in mitochondrial disease complex I causes inflammation & cell death ( to read more about this).
  • Researchers report CD49f as a novel marker of functional & reactive human iPSC-derived astrocytes. Also find that conditioned medium from human reactive A1-like astrocytes is toxic to human & rodent neurons ( to read more about this & click here to read a press summary)
  • Parkinson’s-associated PARKIN is a recognised tumor suppressor in oncology. New research finds it ubiquitinates phosphoglycerate dehydrogenase (PHGDH, the first rate-limiting enzyme of serine synthesis) to suppress serine synthesis & tumor progression ( to read more about this).
  • Researchers report knockdown of microglial Cav2.2 N‐type voltage‐dependent Ca2+ channel ameliorates behavioral deficits in a mouse model of Parkinson’s (interesting contrast to the previous Cav1.2 L‐type channel results – click here to read more about this).

  • Parkinson’s-associated PINK 1 phosphorylates Drp1S616 to regulate mitophagy‐independent mitochondrial dynamics. Reduced levels of Drp1S616 phosphorylation are observed in fibroblasts obtained from both familial & sporadic PD patients ( to read more about this).
  • Researchers have a bioRxiv manuscript characterising a small molecule (benzdiimidazole NAB2) induced changes in Parkinson’s-related trafficking (via the Nedd4 ubiquitin signaling cascade to read more about this).
  • Researchers use fluctuation imaging on Parkinson’s-associated protein LRRK2 to reveal that the G2019S variant alters spatial & membrane dynamics. G2019S expression also increased hetero-interactions with EndoA1 & altered clathrin puncta dynamics ( to read more about this).
  • Researchers report that the more exposed the N-terminus of monomeric Parkinson’s-associated alpha-synuclein, the more aggregation prone it is (Click here to read more about this).
  • Researchers report small molecule inhibition of Parkinson’s-associated ubiquitin E3 ligase receptor component, FBXO7 (aka PARK15) reduces inflammation & confers neuroprotection by stabilizing the mitochondrial kinase PINK1 ( to read more about this).
  • Researchers have a bioRxiv manuscript suggesting that Parkinson’s-associated Parkin binds to Lactotransferrin & ubiquitylates it to regulate iron homeostasis. Parkin deletion=increase in intracellular Fe, while Parkin overexpression=decrease ( to read more about this).
  • Researchers & collaborators report targeted transgene expression in cholinergic interneurons in the rodent & primate striatum (via canine adenovirus serotype 2 vectors carrying a ChAT promoter – to read more about this).
  • Researchers report a better method of measuring deficits in olfactory sensitivity in mouse models of Parkinson’s (using plethysmography of odor-evoked sniffing – to read more about this).

  • Zonisamide (sulfonamide & anti-seizure agent) promotes survival of human‐induced pluripotent stem cell‐derived dopaminergic neurons in the striatum of female rats. implications for Parkinson’s? (Click here to read more about this).
  • Human telomerase reverse transcriptase positively regulates mitophagy by inhibiting the processing & cytoplasmic release of mitochondrial Parkinson’s-associated PINK1 ( to read more about this).
  • Researchers report kinase inhibition of Parkinson’s-associated G2019S-LRRK2 enhances autolysosome formation+function to reduce endogenous a-synuclein intracellular inclusions. Lysosomal morphology & proteolytic activity are altered in G2019S-LRRK2 cells ( to read more about this).
  • Researchers report using in vitro reconstitution & cellular models to show that liquid–liquid phase separation of Parkinson’s-associated α-synuclein precedes its aggregation. Aggravating factors (low pH, mutations) also=phase separation ( to read more about this).
  • Researchers have a bioRxiv manuscript suggesting that α-synuclein undergoes liquid-liquid phase separation by forming a liquid droplet state, which converts into an amyloid-rich hydrogel. Using in vitro & C. elegans model of #Parkinsons, they “found that the sequestration of liposomes mimicking synaptic vesicles slows the maturation process, which is consistent with the observation that various lipid vesicles & membranes are found in Lewy bodies”. “We can thus suggest that the effects of such membranous structures on the ageing process of the droplets involve a slowing down of the amyloid conversion of the gel-like a-synuclein assemblies” – an explanation for Parkinson’s-associated Lewy bodies? ( to read more about this).
  • Researchers have a bioRxiv manuscript on a single-cell analysis of alpha synuclein (SNCA) expression by cell type in human brain samples. Differences in SNCA expression between excitatory vs inhibitory neurons; SNCA interactome enriched for PD-risk loci genes ( 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 to read more about this).
  • New report presenting computationally guided intracerebral drug delivery via chronically implanted microdevices. Implications for Parkinson’s? The GDNF research in Parkinson’s gets a mention, but not the heparin-binding determinants of GDNF which reduces its tissue distribution. Interesting new system though ( to read more about this).
  • Researchers have a bioRxiv manuscript suggesting Rab29 knock-out or transgenic overexpression does not impact basal Parkinson’s-associated LRRK2 activity in wildtype & pathogenic mouse & cell line models ( to read more about this).
  • Researchers from bioRxiv manuscript outlining a single nuclei chromatin profiling study of mouse ventral midbrain providing a useful resource for exploring gene regulation in mesencephalon ( to read more about this).
  • Researchers report that Tectonin beta-propeller repeat-containing protein (TECPR1) promotes “aggrephagy” by direct recruitment of LC3C autophagosomes to lysosomes ( to read more about this).
  • Researchers have a medRxiv manuscript finding no evidence to support a role for LIN28A as a major causal gene for Parkinson’s. Large-scale familial & case-control studies in non-European ancestry populations still necessary (Click here to read more about this).
  • Researchers describe a new machine learning-based analytical pipeline, allowing for detailed image-based cell profiling & toxicity prediction in neurotoxin treated (6-OHDA) brain organoids for Parkinson’s research ( to read more about this).
  • Researchers describe the reproducible generation of human midbrain organoids for in vitro modeling of Parkinson’s ( to read more about this).
  • Researchers have a bioRxiv manuscript suggesting microbiota-derived short chain fatty acids promote Alzheimer’s-associated beta amyloid plaque deposition. SCFA supplement = microglial activation & ApoE upregulation ( to read more about this).

  • The amphipathic GM1 molecule stabilizes amyloid aggregates preventing their cytotoxicity. Imlications for Parkinson’s? (Click here to read more about this).
  • The ribose subunit of inosine can enter into central metabolic pathways to provide ATP & biosynthetic precursors. Cancer cells utilize inosine as a carbon source, & effector T cells can utilize inosine in the absence of glucose in vitro ( to read more about this).
  • Researchers have a bioRxiv manuscript suggesting that loss of JIP3/MAPK8IP3 results in the accumulation of axonal lysosomes & Alzheimer’s-related A-beta42. They also reveal an overlapping role of the homologous JIP4 gene in lysosome axonal transport ( to read more about this).
  • New bioRxiv manuscript suggests “majority of α-syn aggregate-specific antibodies do not differentiate between oligomers & fibrils, thus highlighting the importance of exercising caution when interpreting results” ( to read more about this).
  • New report demonstrates that synaptic vesicle precursors and lysosomes rely on different machineries for axonal transport in mammalian neurons. BORC is required for transport of lysosomes but not SVPs ( to read more about this).
  • Parkinson’s-associated PINK1 “is critical for modulating the bioenergetics & antioxidant responses in PBMCs whereas lack of PINK1 upregulates compensatory glycolysis in response to oxidative stress induced by psychological distress” ( to read more about this).
  • Chronic but not acute exposure to depleted uranium exposure results in a statistically significant degeneration of the dopaminergic neurons & promotes α-synuclein aggregation in C. elegans. No effect on lifespan or reproduction ( to read more about this).
  • Trying to find order in disordered protein – researchers have a bioRxiv manuscript providing structural insights into Parkinson’s-associated alpha synuclein membrane interactions (by MMDS, MSM, & NMR – to read more about this).

  • Researchers have a bioRxiv manuscript suggesting that increased TBK1 activity may promote tau hyperphosphorylation & neuronal loss in Alzheimer’s & related tauopathies. Also report increased TBK1 activity in both AD & FTDP-17 ( to read more about this).
  • Researchers report that the amino acids leucine negatively regulates autophagy (specifically autophagosome biogenesis), via the impact of its metabolite AcCoA on mTORC1. MCCC1, a key enzyme in the Leu-AcCoA pathway & a possible #Parkinsons risk locus, negatively regulates autophagy, & in the supplemental results they show that depletion of MCCC1 enhanced the autophagic clearance of A53T mutant α-synuclein & ameliorated its toxicity ( to read more about this).
  • Researchers report interesting insights in dopaminergic axon guidance & striatal innervation: Nolz1 expression is required. Nolz1−/− mutant striatum repulses DA axons. Implications for Parkinson’s cell transplantation approaches? ( to read more about this).
  • New bioRxiv manuscript from researchers present evidence for a critical involvement of PIPs in Parkinson’s-associated a-synuclein-mediated membrane trafficking (a-Syn colocalizes with PIP2 & the phosphorylated active form of AP2 – to read more about this).
  • Researchers report Netrin-1, produced in the forebrain & axonally transported to the midbrain, instructs the migration of GABAergic neurons into ventral substantia nigra. Required to confine dopamine neurons to the dorsal substantia nigra. “These data demonstrate that neuron migration can be controlled by remotely produced & axon-derived secreted guidance cues, a principle that is likely to apply more generally” ( to read more about this).
  • Researchers reports Cyclophilin D (a mitochondrial peptidyl-prolyl isomerase) binds with soluble Parkinson’s-associated alpha synuclein, preventing aggregation & also promotes disaggregation of preformed fibrils ( to read more about this).
  • A novel approach to measure mitochondrial respiration in frozen biological samples ( to read more about this and click here to read the press summary).

  • Researchers report neurons missing Parkinson’s-asssociated PARKIN exhibit significantly enlarged lysosomes & decreased lysosomal enzyme activity. Curiously β-glucocerebrosidase (GBA) levels are significantly increased in these cells ( to read more about this).
  • Researchers have a bioRxiv manuscript suggesting that over-expression of Gadd45b (a multifactorial protein involved in active DNA demethylation) renders midbrain dopaminergic neurons more vulnerable to acute oxidative stress ( to read more about this).
  • Researchers report mitochondrial AAA+ protein, Skd3 (CLPB in humans) is a potent protein disaggregase. They show that PARL-activated Skd3 dissolves Parkinson’s-associated alpha synuclein fibrils (in vitro – to read more about this).
  • Researchers have a bioRxiv manuscript suggesting Parkinson’s-associated G2019S LRRK2 deregulates endolysosomal trafficking (by impairing RAB8A & RAB10), whilst RAB29 modulates non-Golgi-related trafficking events impaired by pathogenic LRRK2 ( to read more about this).
  • Researchers report overexpression of PGC-1α may activate mitochondrial unfolded protein response, reducing the oxidative stress injury induced by neurotoxins (like MPP+) through LRPPRC signaling, helping to maintain mitochondrial homeostasis ( to read more about this).
  • Could neurotoxicants (pesticides, etc) be impairing brain immune response by altering glial cell metabolism?Researchers report they cause disruption to anti-inflammatory processes & metabolism in glial cells. Implications for Parkinson’s? ( to read more about this).

  • Single-vesicle imaging study quantifying calcium’s regulation of vesicle clustering demonstrates at low concentrations calcium competes with Parkinson’s-associated alpha synuclein to bind to anionic lipids, causing α-synuclein to dissociate from membranes. The research “suggests that calcium & negatively charged lipids play critical roles in vesicle clustering, & provides new insights into how alpha synuclein regulates synaptic vesicle trafficking & synaptic transmission” ( to read more about this).
  • Researchers reports endocytic regulation of cellular ion homeostasis controls lysosome biogenesis ( to read more about this).
  • Large collaboration highlights new molecular factors & pathways altered by Parkinson’s-associated PARK2 mutations ( to read more about this).
  • New medRxiv manuscript suggests that the endocannabinoid system participates in the pathophysiology of Parkinson’s symptoms, but its role in the pathophysiology of levodopa-induced dyskinesia is still unclear ( to read more about this).
  • Researchers report accurate mass spectrometry-based Rab10 phosphorylation stoichiometry determination as readout for LRRK2 activity in Parkinson’s (Click here to read more about this).
  • Researchers presenting a novel high-throughput & hypothesis-free approach to detect the existence of Parkinson’s genetic risk linked to any particular biological pathway (Click here to read more about this).

Disease mechanism

  • Researchers report that NMDA receptors are altered in the substantia nigra pars reticulata & their blockade ameliorates motor deficits in models of Parkinson’s (Click here to read more about this).
  • Researchers report PARP1 as a modulator of transcription factor EB (TFEB). PARP1 inhibitor Veliparib restores autophagic flux in α‐synuclein A53T model of Parkinson’s ( to read more about this).
  • Researchers describe a nanobody (NbSyn87) that binds to Parkinson’s-associated alpha synuclein (& the proteasomal subunit Rpn10). They use this biosensor to “finally reveal the presence of transmittable αSyn in human cerebrospinal fluid” ( to read more about this).
  • Researchers report pronounced Parkinson’s-associated α-synuclein pathology in a seeding-based mouse model is not sufficient to induce mitochondrial respiration deficits in the striatum & amygdala ( to read more about this).
  • Researchers report Parkinson’s-associated LRRK2 kinase inhibition rescues deficits in lysosome function due to heterozygous GBA1 expression (in human iPSC-derived neurons), but does not reduce α-synuclein accumulation ( to read more about this).

  • Researchers & collaborators report transglutaminase 2 deletion in Parkinson’s-associated α-synuclein transgenic mice reduces levels of brain α-synuclein aggregates ( to read more about this).
  • Researchers report mouse LRRK2 knockout neurons are more resistant to Parkinson’s-associated α-synuclein aggregation, while G2019S-LRRK2 knockin neurons are more vulnerable to fibril-induced α-synuclein accumulation ( to read more about this).
  • New study reports LOSS of the Sigma1R expression prevents neurotoxin-mediated cell death. Further, Sigma1 antagonist (NE-100) activates TRPC1-mediated Ca2+ entry that inhibits ER stress & neurodegeneration in Parkinson’s model ( to read more about this).
  • Researchers have a bioRxiv manuscript suggesting that the presynaptic effects of Parkinson’s-associated α-synuclein are dependent on specific patterns of neuronal activity ( to read more about this).
  • Researchers report that kinase inhibition of Parkinson’s-associated G2019S-LRRK2 restores autolysosome formation & function to reduce endogenous alpha-synuclein intracellular inclusions (Click here to read more about this).
  • Zebrafish missing ATP13A2 (PARK9) – autosomal recessive causative gene for juvenile-onset Parkinsonisms – exhibit degeneration of dopaminergic neurons, lysosomal dysfunction, & the possibility of intracellular trafficking impairment ( to read more about this).
  • Researchers have a bioRxiv manuscript presenting an adaptable platform based on p.A53T iPSC-derived neurons for drug screening, that identified the small molecule inhibitor BX795 as an interesting neuroprotective candidate for Parkinson’s ( to read more about this).
  • Researchers report α-synuclein overexpression in the retina leads to vision impairment & degeneration of dopaminergic amacrine cells. Implications for Parkinson’s? ( to read more about this).

  • Researchers present evidence for reconsidering RIPK inhibition in Parkinson’s. Data from SH-SY5Y & G2019s-LRRK2 fibroblasts points to mitochondrial morphology issues in Necrostatin-1 treated cells ( to read more about this).
  • Researchers report the combination of the iminosugar 1-Deoxynojirimycin & Ibuprofen decreases microglial activation, phagocytosis & dopaminergic neurodegeneration in a Parkinson’s mouse model (MPTP – to read more about this).
  • COUP-TFII, an orphan nuclear receptor, is upregulated in dopamine neurons in Parkinson’s patients, may contribute to oxidative stress. Now researchers report overexpression of COUP-TFII results in mitochondrial dysfunction in mouse dopamine neurons. Interestingly, they report reducing COUP-TFII in dopamine neurons slowed the deterioration in motor functions of MitoPark mice (a mitochondrial model of Parkinson’s – to read more about this).
  • Evidence that GSK-3β may contribute to Parkinson’s-associated dopamine neurodegeneration. Conditional knockout mice are resistant to MPTP insult, & GSK-3β inhibitor Tideglusib exhibits neuroprotection in MPTP model of PD ( to read more about this).
  • Researchers systematically investigated the modulating effects of Parkinson’s pathogenic mutations on the cell-to-cell transmission of α-synuclein & found increased secretion levels overall; variable effects on aggregation ( to read more about this).
  • Evidence of grafted hESC-derived dopaminergic neurons acquiring α-synuclein pathology in preclinical cell transplant studies in a humanized α-synuclein rat model of Parkinson’s ( to read more about this).

 

Clinical research

  • Researchers report that serum urate/uric acid levels may have the potentially gender-specific close relationship with white matter integrity in the early stage of Parkinson’s (Click here to read more about this).
  • Researchers have a bioRxiv manuscript suggesting a lack of evidence for genetic association of saposins A, B, C and D with Parkinson’s ( to read more about this).
  • Under represented communities – Researchers involved in the Latin American Research consortium on the GEnetics of Parkinson’s Disease (LARGE-PD) have a medrxiv manuscript outlining the genetics of Parkinson’s in Latin American populations (Click here to read more about this and click here to read more about this initiative).

  • Using the medical records‐linkage system (Rochester Epidemiology Project), researchers report no associations between infections leading to hospitalization or sepsis & the development of any α‐synucleinopathies (like Parkinson’s – click here to read more about this).
  • Researchers report a small proof-of-concept study evaluating wearable haptic anklets for gait & freezing improvement in Parkinson’s ( to read more about this).
  • Researchers have a bioRxiv manuscript describing a deep seq analysis of non-coding RNAs from ~1,600 individuals with Parkinson’s (from the PPMI study) revealing associations with sub-types, aging, & disease progression. Rich dataset (>320 billion reads) & everyone is here: miRNAs, piRNAs, rRNAs, snoRNAs, tRNAs, scaRNAs, snRNAs, etc. They validated their main findings using the independent NCER-PD cohort ( to read more about this).
  • Interesting study applying the Predict PD study algorithm of risk indicators for Parkinson’s in a prospective community‐based study (the Bruneck study). Risk scores were calculated at baseline (2005, n=574); 5 & 10‐year follow‐ups. 20 cases identified (Click here to read more about this).
  • More epidemiological data on β-agonists & Parkinson’s: A nationwide nested case–control study finds a protective association in non-diabetic patients (aOR 0.75 [0.60–0.93]) & an opposite association in diabetic patients (aOR 1.61 [1.02–2.55]). The study found no increased risk of Parkinson’s occurrence after β-antagonist exposure, except for propranolol (potential protopathic bias). The authors suggest diabetic effect deserves further research (Click here to read more about this).

  • Researchers report sedentary time is associated with worse attention in pilot study of individuals with mild-to-moderate Parkinson’s ( to read more about this).
  • Researchers have a medRxiv manuscript suggesting higher levels of nitrite & nitrate in the cerebrospinal fluid of people with Parkinson’s & levedopa-induced dyskinesias ( to read more about this).
  • Researchers have a bioRxiv manuscript suggesting that ultra-rare variants may play a significant role in early-onset cases of Parkinson’s (EOPD), & that distinct etiological bases may exist for EOPD & sporadic PD ( to read more about this).
  • Researchers provide an update on the long-term effects of spinal cord stimulation in advanced Parkinson’s ( to read more about this).
  • Researchers present a personalised approach for identifying disease-relevant pathways in heterogeneous diseases. Implications for Parkinson’s? ( to read more about this).
  • Researchers report that metabolic syndromes (obesity, hypertension, glucose impairment, etc) do not appear to influence the phenotype of LRRK2- (n=55) or GBA- (n=97) associated Parkinson’s (Click here to read more about this).
  • A meta-analysis of real-world evidence suggests thiazolidinedione use is associated with reduced risk of Parkinson’s in people with diabetes ( to read more about this).

  • New bioRxiv manuscript suggests neurofilament light chain, vesicle-associated membrane protein 2 & calbindin 2, (+ the miRNAs that regulate them) may be potential enteric biomarkers of early Parkinson’s ( to read more about this).
  • The NCER-PD Consortium report that Parkinson’s-associated alterations of the gut microbiome can translate into substantial functional differences affecting host metabolism & disease phenotype ( to read more about this).
  • Biogen researchers report quantitative measurements of Parkinson’s-associated LRRK2 in human cerebrospinal fluid, & demonstrate increased levels in G2019S carriers (106 CSF samples from the LRRK2 Cohort Consortium). Also interesting that this potentially very useful assay found that CSF levels of LRRK2 increased with age across all of the participants ( to read more about this)
  • Researchers report MWAS evidence for overabundance of opportunistic pathogens in the Parkinson’s gut microbiota. Short-chain fatty acid (SCFA)-producing bacteria were reduced in PD ( to read more about this).
  • Researchers have a bioRxivmanuscript suggesting that bilateral but not unilateral subthalamic stimulation promotes apathy in both rodents & Parkinson’s patients ( to read more about this).
  • New bioRxiv manuscript suggests neural signatures of pathological hyperdirect pathway activity in Parkinson’s ( to read more about this).
  • “ParkinSong”: Outcomes of a 12-month controlled trial of therapeutic singing groups in Parkinson’s demonstrate improvements in speech loudness & voice-related Quality of Life for participants (& QoL for carers! – to read more about this).

  • Gastrointestinal inflammation has been implicated in Parkinson’s. Researchers report Clostridium difficile infection may be associated with an increased short‐term PD risk (lots of caveats attached –  to read more about this).
  • Residual activity of the β-glucocerebrosidase enzyme measured in blood inversely correlates with clinical severity types of GBA mutations in Parkinson’s. Analysis involved 481 participants (47 GBA-PD, 247 idiopathic PD, & 187 controls). Longitudinal follow ups comprised 195 participants with 548 longitudinal measurements over a median follow-up period of 2.0 years. “β-Glucocerebrosidase activity is a quantitative endophenotype that can be non-invasively monitored and therapeutically targeted” (Click here to read more about this).
  • Skin cancers have a higher prevalence in PD, but now researchers report a nested case-controlled study finding that skin cancer appears to delay the time to Parkinson’s onset but not its clinical progression ( to read more about this).
  • Researchers using Parkinson’s Progression Marker Initiative (PPMI) data find baseline cerebrospinal fluid Alzheimer’s biomarkers may have prognostic value in early PD & subtle changes of these markers in PD may deviate from healthy aging (Click here to read more about this).
  • Researchers have a bioRxiv manuscript suggesting that exaggerated, movement-modulated high frequency oscillations in the internal globus pallidus may be a pathophysiological feature of Parkinson’s. An electrophysiological biomarker? ( to read more about this).
  • I listened to Oluwadamilola Ojo speak at the recent IPDGC meeting, and I was hugely impressed with the efforts that she & her colleagues are making on “The Nigeria Parkinson’s Disease Registry“. A new paper outlines a platform they are developing ( to read more about this).
  • Researchers report on the feasibility of muscle mitochondrial respiratory chain phenotyping across the cognitive spectrum in Parkinson’s ( to read more about this).
  • Researchers report subtypes of dementia with Lewy bodies are associated with α-synuclein & tau distribution (Click here to read more about this).
  • A self‐administered scale for orthostatic tremor. Researchers report on the development & validation of the orthostatic tremor severity & disability scale (OT ‐10 – click here to read more about this).
  • A novel rare variant of LRRK2-associated with familial Parkinson’s: p.R1501W. Located in the ROC domain, kinase activity not elevated, presents a late-onset & a mild course of PD ( to read more about this).
  • Researchers explore a model for developing a geographically dispersed & well-characterized Parkinson’s cohort (n=263 in 33 states) ready for participation in future clinical trials of gene-directed therapies ( to read more about this).
  • New study from researchers provides clinical rationale for strictly avoiding the use of trimetazidine in Parkinson’s. “Discontinuation of trimetazidin results in clinically relevant improvements in Parkinsonian symptoms” (Click here to read more about this).
  • Researchers highlight the importance of accurate electrode placement & careful stimulation titration in the prevention of neuropsychiatric side-effects after subthalamic nucleus-deep brain stimulation ( to read more about this).

  • Trying to find consensus on safety around driving & Parkinson’s -researchers attempted to determine predictors of driving ability to guide development of predictive tools for implementation into clinical practice ( to read more about this).
  • In 2007, the National Neuroscience Institute created the “Community Care Partners Programme” to bring the patient-centric care & nurse-led integrated community care programmes for the Parkinson’s community to Singapore. This mini-review outlines progress (Click here to read more about this).
  • New bioRxiv manuscript suggests multiple Parkinson’s risk alleles may modify clinical manifestations to influence PD motor subtype. Novel variant at STK32B offers possible overlap between essential tremor & tremor-dominant PD ( to read more about this).
  • Researchers report appendectomy & potentially also tonsillectomy were associated with a lower risk of Parkinson’s. A nested case-control study included 78,650 PD patients (& 40x as many controls) on the Swedish Patient Register ( to read more about this).
  • New medRxiv manuscript supports the association of single PARK2 mutations with Parkinson’s, but it also highlights confounding effects – thus “caution is needed when interpreting current risk estimates” ( to read more about this).
  • New medRxiv manuscript questions the “Parkinson’s-associated” designation for DNAJC13, UCHL1, HTRA2, GIGYF2 & EIF4G1, based on analyses across 3 different cohorts (Click here to read more about this).
  • Researchers report that psychiatric & cognitive features, rather than motor deficits, distinguish clinical subtypes of Parkinson’s, & predict greater risk of subsequent dementia & mortality (prospective cohort; n=162) ( to read more about this).
  • A Movement Disorder Society commissioned systematic review & meta‐analysis of integrated care in Parkinson’s ( to read more about this).
  • Clinical tools for identifying a SWEDD. Researchers explore clinical signs for identifying patients with “scans without evidence of dopaminergic deficit” (SWEDD) – not Parkinson’s. Their conclusion: “it’s very difficult” ( to read more about this).
  • Deep brain stimulation in early-stage Parkinson’s – 5 yr outcomes “suggest that early DBS reduces the need for & complexity of PD medications while providing long-term motor benefit over standard medical therapy” (Click here to read more about this).
  • Researchers have an interesting manuscript on ChemRxiv provided the latest study into the “smell of Parkinson’s“. They report two classes of lipids (phosphatidylcholine and cardiolipin) that differ significantly in the sebum of people with PD (Click here to read more about this).

 

New clinical trials

  • New clinical trial registered: IRLAB Therapeutics are initiating their Phase 2b clinical trial of Mesdopetam (IRL790; a D3 receptor targetted small molecule) in patients with Parkinson’s & levodopa induced dyskinesia (Click here to learn more about this).
  • New clinical study registered: researchers initiate an observational study trying to identify leucocyte & urine biomarkers in 150 Parkinson’s patients with LRRK2 G2385R genetic variant (Click here to read more about this).
  • New clinical trial registered: AstraZeneca has registered a Phase 1 multicenter, randomized, double-blind, placebo-controlled study of multiple ascending doses of MEDI341 (alpha synuclein immunotherapy) in 36 people with Parkinson’s (Click here to read more about this).

 

Clinical trial news

  • A small (n=34) randomised trial reports prolonged-release melatonin is an effective & safe treatment option in Parkinson’s patients with a poor sleep quality. Beneficial effects on sleep quality were associated with improved non-motor symptoms & QoL (Click here to read more about this).
  • AlzeCure Pharma announces positive results from their first clinical study of ACD856 (evaluating half-life). Further Phase I studies are planned (tolerability). ACD856 – a positive modulator of neurotrophin signaling – is being developed for Alzheimer’s ( to read more about this).

  • Care of Late-Stage Parkinsonism (CLaSP) consortium members report the results of a large multinational study on motor & non-motor complications in the late stage of Parkinson’s (Click here to read more about this).
  • The study protocol of the DUtch PARkinson Cohort (DUPARC) has been published. This is a prospective, observational study of de novo Parkinson’s patients focused on the identification & validation of biomarkers for PD subtypes, progression & pathophysiology ( to read more about this).
  • A pilot study testing a gyroscopic spoon in Parkinson’s patients with tremor suggests that clinicians should advise caution when patients are considering the purchase of tremor assist devices (Click here to read more about this).
  • “Adapted resistance training with instability is able to cause significant clinical improvement & brain plasticity in freezers” The conclusion of a randomized, controlled trial of exercise for individuals with Parkinson’s & freezing of gait (Click here to read more about this).
  • A pilot clinical study exploring freezing of gait in people with Parkinson’s reports tactile feedback modulates the execution, but not preparation, of gait initiation (Click here to read more about this).

 

Other news

  • The Cure Parkinson’s Trust held a workshop of international key opinion leaders with direct knowledge and practical experience in the field of GDNF and associated neurotrophic factors. The goal of the meeting was to build a consensus on what is known pre-clinically and clinically about GDNF, and what still needs further investigation in the field to help find a pathway forward. A report of that meeting has been published (Click here to read more about this).
  • Seelos Therapeutics announced initiation of preclinical study of their alpha synuclein-targetted gene therapy approach “SLS-004” for Parkinson’s. It involves lentiviral delivery of DNA methyltransferase 3A to promote methylation of SNCA ( to read more about this and click here to read a press summary).

  • Edinburgh medtech firm Manus Neurodynamica has closed a £750,000 funding round to develop its digital pen which provides an early warning of Parkinson’s ( to read more about this).
  • Press release from IRLAB Therapeutics outlines new Phase IIb/III clinical study for mesdopetam (IRL790) which is in development for the treatment of levodopa induced dyskinesia (LIDs) in Parkinson’s ( to read more about this).

  • Researchers present “Protein Interaction Network Online Tool” (PINOT) – an intuitive resource for integrating protein-protein interactions. Parkinson’s-associated genes/proteins illustrate its utility ( to read more about this).
  • “Weeding through the haze” – researchers have a medRxiv manuscript presenting results from a survey on cannabis use among people living with Parkinson’s in the US ( to read more about this).

 

Review articles/videos

  • The Evolution-Driven Signature of Parkinson’s Disease” – a perspective of PD in the context of an evolutionary mismatch of CNS functions, allows for a re-interpretation of PD-prone cellular phenotypes & prototypical clinical symptoms. New conceptual framework for research ( to read more about this).
  • Researchers provide a very thorough review on harnessing regulatory T cell neuroprotective activities for treatment of neurodegenerative conditions, including Parkinson’s ( to read more about this).

  • Researchers provide a mini review of small molecule chaperones that are being investigated for the treatment of Gaucher disease & GBA1-associated Parkinson’s (ambroxol gets a good discussion – to read more about this).
  • Researchers explore the “Amyloid Senescence Hypothesis“: Is the elimination of senescence-inducing stressors like amyloid proteins in Alzheimer’s & Parkinson’s likely be ineffective in abrogating the spread of senescence? ( to read more about this).
  • Researchers provide a review discussing specific Parkinson’s-associated LRRK2 protein-protein interactions & considering the representation of LRRK2 interactions in public repositories ( to read more about this).

  • Researchers review LRRK2 & discuss how it sits at the interface between peripheral & central immune function in Parkinson’s ( to read more about this).
  • More LRRK2 stuff: Researchers have a useful review on the normal (& disease-related) role of Parkinson’s-associated LRRK2 protein on autophagic & lysosomal function ( to read more about this).
  • “I Want to Do It, But I Want to Make Sure That I Do It Right.” Views of patients with Parkinson’s regarding early stem cell clinical trial participation (Click here to read more about this).
  • Exploring sphingolipid implications in neurodegeneration (interesting section on Parkinson’s included – click here to read more about this).
  • A review of the relationship between Vitamin D & Parkinson’s symptoms ( to read more about this).

  • A 40 rear perspective of neuronal replacement as a tool for basal ganglia circuitry repair from two of the best in the business ( to read more about this).
  • A neurologist with Parkinson’s “I could feel Parkinson’s disease creeping up on me, so when I finally summoned up the courage to have a colleague assess me & make the diagnosis, it was of no surprise; in fact, it was almost a relief” (Click here to read more about this).
  • “The future of targeted gene-based treatment strategies & biomarkers in Parkinson’s ( to read more about this).
  • Interesting viewpoint – “Happiness: A Novel Outcome in Parkinson’s Studies?” ( to read more about this).

  • Parkinson’s disease: etiopathogenesis & treatment” A very useful overview of… well basically everything Parkinson’s-related ( to read more about this).
  • An interesting review of glia-derived extracellular vesicles in Parkinson’s ( to read more about this).
  • Researchers present the argument for metformin as a potential neuroprotective agent in prodromal Parkinson’s ( to read more about this).
  • Researchers review links between pathogenic LRRK2, Rab protein phosphorylation & endolysosomal trafficking alterations. They propose a model whereby LRRK2-associated Parkinson’s may present with variable Lewy pathology ( to read more about this).
  • Virtual reality in research and rehabilitation of gait and balance in Parkinson (Click here to read more about this).

 

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

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

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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.


2 thoughts on “Monthy research review – June 2020

  1. Hello,
    my post is off subject . My mother 83 is much better last 2 years ( i can say 90 percent better last (730 days) she can move much much much much and much more better month after month For example her really very terrible Swallowing problem is completely solved. She wasnt able to eat normal from 4 years .Starting from Jan-2017 She was taking 375 mg Ambroxol for 180 dayes whit combination of Nivalin .. Nivalin is making new motor neurons connections in the brain

    Like

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