Monthly Research Review – January 2021

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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 the previous 4 weeks.

The post is divided into eight parts based on the type of research:

Today’s post is a review of Parkinson’s research during the month of January 2021.

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So, what happened during January 2021?

In world news:

January 6th – the platypus genome was published. Reseachers explore how one of mother nature’s oddities became so odd (Click here to read more about this).

January 6th – Using a recently developed gene-editing technique, researchers reported that they could partially correct the accelerated aging disorder of progeria, extending the lifespan of mice with the associated genetic variation (Click here to read more about this).

January 7th – While the world is more focused on the rollout of the company’s COVID vaccine, researchers at BioNTech published a research report in which they had designed an mRNA vaccine that delayed the onset of and reduced the severity of multiple sclerosis-like disease in mice (Click here to read more about this).

January 26 – The number of confirmed COVID-19 cases exceeded 100 million worldwide.

January 28th – A day that some of the absurdity of the stock market was openly revealed. Wall Street institutions cried “it’s not fair if everyone else can manipulate the market”, as the GameStop share price rise messed up their own manipulations (Now we suddenly need regulation?!?). Free markets indeed (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 January 2021, there were 1,235 research articles added to the Pubmed website with the tag word “Parkinson’s ” attached (10,584 for all of 2020). In addition, there was a wave to news reports regarding various other bits of Parkinson’s research activity (clinical trials, etc).

The top 6 pieces of Parkinson’s news

1. Green light for BlueRock Therapeutics:

The US FDA cleared the Investigational New Drug (IND) application of the biotech firm BlueRock Therapeutics & pharma company Bayer, giving them the green light to proceed with Phase I clinical testing to evaluate safety, tolerability & preliminary efficacy of DA01 (stem cell-derived dopaminergic neurons) in Parkinson’s. This will be the “first trial in the United States to study pluripotent stem cell-derived dopaminergic neurons in patients with Parkinson’s” (Click here to read more about this).

2. Drainage issues in Parkinson’s?

The lymphatic system plays an important role in the immune response to injury and aids in the clearance of waste. Using MRI imaging, researchers report that there is a reduction in meningeal lymphatic vessel flow in cases of idiopathic Parkinson’s (compared to controls). In mice, they found that the introduction of α-synuclein pathology was followed by delayed meningeal lymphatic drainage. In addition, the researchers also found that blocking meningeal lymphatic flow in mice treated with preformed alpha synuclein fibrils exacerbated α-synuclein path & outcomes (Click here to read more about this).

3. STEADY-PD3 study Post hoc analysis

The STEADY-PD3 study was a large, multi-year Phase III trial exploring the use of the calcium channel blocker isradipine in individuals recently diagnosed with Parkinson’s. The primary endpoints of the study indicated that the treatment had no effect of the progression of Parkinson’s, but now post-hoc analysis of the STEADY-PD3 data indicates that higher isradipine plasma exposure resulted in decreased cumulative levodopa equivalent dose & extended the period of time between diagnosis and the initiation of anti-Parkinson’s treatment (Click here to read more about this).

4. Forget “Special K”. Time to focus on “LysoK”

Researchers have identified a lysosomal potassium channel complex that they have called LysoK-GF. It involves the pore-forming protein TMEM175 and it is activated by growth factors. Specific genetic variations in the TMEM175 gene have previously been associated with increased risk of developing Parkinson’s. Now, in their new study, scientists report that reductions in lysoK-GF function (due to a specific genetic variant called rs34311866) predisposes neurons to stress-induced damage, and this results in the accelerated accumulation of pathological α-synuclein. In addition, they identified a second variant (rs34311866) which reduces the risk of developing Parkinson’s, by increasing lysoK-GF activity (Click here to read more about this).

5. Behold, my transkingdom!

Gene expression & electron microscopy studies highlight the “transkingdom” interactions of two species from Lactobacillus genus of gut bacteria with mitochondria in the liver leading to the improvement of lipid metabolism. Researchers ask if this could lead to potential probiotic strains for treating Type 2 diabetes? Given the curious association between diabetes & Parkinson’s it would be interesting to explore this western diet/gut microbiota-liver interaction in the context of PD, particularly as it is noted here that both palmitic & oleic acids are decreased by Lactobacilli, both of which have been implicated in Parkinson’s (Click here to read more about this).

6.  Going fully in vitro?

An in vitro system to investigate organ-organ– & organ-immune–specific interactions. Researchers present a mesofluidic microphysiological systems platform technology to study gut-liver-cerebral interactions in the context of Parkinson’s. Using patient-derived cells carrying the Parkinson’s-associated A53T mutation, they report systemic interaction enhances aspects of in vivo–like behaviour of brain cells, & that microbiome-associated short-chain fatty acids increase expression of pathology-associated pathways in PD (Click here to read more about this).

Basic biology news

  • 14-3-3 inhibition in dopamine neurons accelerated Parkinson’s-associated α-synuclein aggregation & enhanced PFF-induced reduction in dopaminergic cells. 14-3-3θ overexpression (via AAV) delayed α-syn aggregation & blocks neurodegeneration (Click here to read more about this)
  • New report finds that (in vitro & Parkinson’s C. elegans model) α-synuclein undergoes liquid‒liquid phase separation by forming a liquid droplet state, which converts into an amyloid-rich hydrogel with Lewy-body-like properties (Click here to read more about this).
  • Pharma company Eli Lilly bought Disarm Therapeutics last October & now we learn about their small molecule SARM1 inhibitors that allow recovery of axonal degeneration after exposure to rotenone (Click here to read more about this).

  • New biorxiv manuscript highlights importance of the surrounding environment & describes how ion content can influence water mobility + the misfolding rate of amyloidogenic proteins, such as Parkinson’s-associated alpha synuclein (Click here to read more about this).
  • Researchers report overexpression of human α-synuclein in a mouse model of Parkinson’s leads to vascular pathology, blood brain barrier leakage, & pericyte activation; Future studies “needed to investigate the in vivo secretome of pericytes” (Click here to read more about this).
  • Temperature is a key determinant of alpha- & beta-synuclein membrane interactions in neurons; at lower temperatures (4 °C or room temperature), α-syn is largely membrane-associated, while @ 37°C α-syn solubility is markedly increased (Click here to read more about this).
  • New research indicates that Parkinson’s-associated α-synuclein deposits retain their seeding potential after the formalin fixation of tissues; No statistically significant difference in the seeding efficiency of specific regions was found (Click here to read more about this).
  • Biotech firm Khondrion publishes data on the mechanism of action & potential applications of selective inhibition of microsomal prostaglandin E synthase-1-mediated PGE2 biosynthesis by sonlicromanol’s metabolite KH176m (Click here to read more about this).

  • New biorxiv manuscript highlights the early effects of the Parkinson’s-associated VPS35 D620N mutation on cellular functions that are specific to neurons. Interesting effect of LRRK2 kinase inhibition (Click here to read more about this).
  • BNIP3L/NIX-mediated mitophagy protects against glucocorticoid-induced synapse defects; NIX downregulation inhibits mitophagy independently from the Parkinson’s-associated PARKIN-PINK-mediated pathway (Click here to read more about this).
  • Fibroblasts (skin cells) from idiopathic cases of Parkinson’s have decreased GCase activity primarily driven by altered LIMP2-mediated transport of GBA to lysosome; reduced GCase activity in GBA N370S-derived PD cells occurs through a different mechanism (Click here to read more about this).
  • Isoform-selective decrease of glycogen synthase kinase-3 beta (GSK-3β) reduces synaptic tau phosphorylation, trans-cellular spreading & aggregation; wonder if this applies to Parkinson’s-associated alpha synuclein? (Click here to read more about this).
  • Researchers provide further evidence that inhibition of the L‐tryptophan‐catabolizing enzyme tryptophan 2,3‐dioxygenase (TDO) has beneficial effects in models of Parkinson’s (Click here to read more about this).
  • The lords of LRRK are at it again: Researchers explore LRRK1 & Parkinson’s-associated LRRK2 phosphorylation of distinct Rab proteins; “Widely used LRRK2 inhibitors do not inhibit LRRK1” but a promiscuous inhibitor termed GZD-824 does (Click here to read more about this).

  • VCP-binding co-factor (SVIP) is a molecular determinant of lysosomal dynamic stability, neurodegeneration & lifespan; researchers propose a model for Valosin-Containing Protein disease based on recruitment of VCP to intracellular organelles (Click here to read more about this).
  • New biorxiv manuscript suggests microglial beta-glucocerebrosidase (GCase) inhibition impairs microglia-to-neuron communication increasing the sensitivity of neurons to oxidative/toxic insults; implications for GBA-associated Parkinsons? (Click here to read more about this).
  • A new biorxiv manuscript presents long-timescale, atomic-level molecular dynamics simulations of Parkinson’s-associated (monomeric) α-synuclein binding the small-molecule drug fasudil (Click here to read more about this).
  • New research sheds light on function of Parkinson’s-associated α-synuclein, they also provide a possible link between α-syn function & vesicle trafficking malfunction in PD; colocalization with caveolin positive vesicles & a small fraction with EEA1 & Rab7 (Click here to read more about this).
  • The Parkinson’s Disease DNA variant browser – presented by the team at the International Parkinson Disease Genomics Consortium (Click here to read more about this).

  • Using 3 co-culture setups, researchers report that embryonic microglia secret factors that enhance dopaminergic differentiation of somatic & induced pluripotent stem cell-derived human neural stem cells (Click here to read more about this).
  • Microglial activation elicits a negative affective state via prostaglandin-mediated modulation of striatal neurons; Chemogenetic activation of striatal microglia induces an aversive affective state, while inhibition blocks inflammation-induced aversion (Click here to read more about this).
  • Further evidence that Parkinson’s-associated α‐Synuclein (fibrils, but not monomers) evokes NLRP3 inflammasome‐mediated IL‐1β secretion (this time in primary human microglia – Click here to read more about this).
  • Researchers point towards the M-type potassium current as an important thalamic excitability regulator in the parkinsonian state (Click here to read more about this).
  • The orphan nuclear receptor Nurr1 agonist amodiaquine found to mediate a neuroprotective effects in 6-OHDA neurotoxin model of Parkinson’s (by enhancing the phosphorylation of P38 mitogen-activated kinase but not PI3K/AKT signaling pathway – Click here to read more about this).

  • Researchers explore striatal neuroinflammation in mice developing Parkinson’s-associated L-DOPA-induced dyskinesia; cannabidiol & TRPV-1 antagonist capsazepine diminished LID intensity & reduced TNF-α levels without impacting other inflammation markers (Click here to read more about this).
  • Selectivity of partners: A new biorxiv manuscript presents an interaction map of 65 proteins against different species of Parkinson’s-associated alpha synuclein (SNCA), & propose new model of Lewy body formation (Click here to read more about this).
  • New biorxiv manuscript suggests Ajuba as a regulator of Parkinson’s-assocaited PINK1-Parkin signaling; Zika virus can antagonize mitophagy (preventing Ajuba translocation to mitochondria for PINK1 activation – click here to read more about this).
  • New report “establishes infrared nanospectroscopy as a powerful tool for characterising interactions of drugs with protein aggregates at the single oligomer level, & identifying key interaction signatures” (Click here to read more about this).
  • Loss of Parkinson’s-associated LRRK2 promotes carcinogen-induced lung tumorigenesis in models cancer. Researchers ask whether long-term LRRK2 inhibition may require additional monitoring (Click here to read more about this).
  • Scientists at the pharmaceutical company Merck explore onset, progression, & reversibility of morphological changes in the lung following pharmacological inhibition of LRRK2 (in mice); “de-risking of safety & tolerability concerns for chronic LRRK2 kinase inhibition in Parkinson’s” (Click here to read more about this).

Disease mechanism

  • Gastrointestinal & metabolic function in the MPTP-treated primate model of Parkinson’s: “While the MPTP monkey model reliably displays motor & certain non-motor symptoms of PD, the current study did not demonstrate the GI symptoms associated with PD” (Click here to read more about this).
  • Dopamine metabolite DOPAL inhibits Alzheimer’s-associated amyloid-β fibril formation, but is able to stabilise oligomeric species that exert toxic effects in vitro, (increasing cytosolic calcium levels & ROS – Click here to read more about this).
  • Aged transgenic mice (with mutated eIF2α kinase heme-regulated inhibitory (HRI)) exhibit accumulation of misfolded Parkinson’s-associated α-synuclein in the sacral spinal cord horn, which receives visceral sensory afferents from the bladder & distal colon. “Results suggest that HRI contributes to a general cytosolic unfolded protein response that could be leveraged to bolster the clearance of cytotoxic protein aggregates” (Click here to read more about this).
  • New report finds that doxycycline decreases number & size of Parkinson’s-associated alpha synuclein inclusions in cells, lowers the production of mitochondrial-derived reactive oxygen species, & induces redistribution of aggregates in C.elegans (Click here to read more about this).

  • Genetic deletion of Polo-like kinase 2 reduces Parkinson’s-associated alpha-syn serine-129 phosphorylation in presynaptic terminals but has no effect on Lewy body phosphorylation levels. PLK2 deletion slows the rate of neuronal death (Click here to read more about this).
  • Researchers report that α-synuclein expression in Parkinson’s is controlled by SNCA′s histone posttranslational modifications & modulation of the histone landscape of SNCA reduces α-synuclein expression (Click here to read more about this).
  • Intranasal administration of Parkinson’s-associated α-synuclein preformed fibrils triggers microglial iron deposition in substantia nigra of primates; “inhibition of iron deposition may be a potential approach for the early prevention & treatment of PD” (Click here to read more about this).
  • Researchers report the development of a SUMO1-derived peptide (SUMO1(15–55)) which reduces α-synuclein-induced cytotoxicity in cell-based & drosophila models of Parkinson’s (Click here to read more about this).
  • Researchers report that activation of mGluR5 partially inhibits Parkinson’s-associated α-synuclein-induced inflammatory response; α-syn facilitated mGluR5 degradation (via the lysosomal pathway) in PD rat models (Click here to read more about this).
  • Researchers from Biogen identify ITPKB as a negative regulator of α-synuclein aggregation & highlight modulation of ER-to-mitochondria calcium flux as a therapeutic strategy for the treatment of sporadic Parkinson’s (Click here to read more about this).

  • A valuable resource to elucidate the molecular steps of development, maturation, & function of human dopamine neurons: scRNAseq of ~20K ventral midbrain-patterned stem cells at different stages of maturation (Click here to read more about this).
  • Researchers present a cell-penetrating, antioxidant SELENOT mimetic that protects dopamine neurons & ameliorates motor dysfunction in models of Parkinson’s (Click here to read more about this).
  • “Improved NMDAR antagonist NitroSynapsin, which selectively inhibits extrasynaptic over physiological synaptic NMDAR activity, protects synapses from oligomeric αSyn-induced damage”; novel experimental therapeutic for Parkinsons? NitroSynapsin has been licensed to EuMentis Therapeutics, & has also exhibited interesting results in preclinical models of Alzheimer’s (Click here to read more about this).
  • Issues with DNA methylation in PD: Researchers present data implicating DNA Methyltransferase 1 in Parkinson’s; DNMT1 dysregulation via mediation of miR-17; miR-17 found to be elevated in the neurotoxin-induced PD models & the plasma of PD patients (Click here to read more about this).
  • Interesting: Lots of focus on Sigma 1 receptor in Parkinson’s research at the moment, but what about Sigma 2 receptor? Cognition Therapeutics researchers report Sigma‐2 receptor antagonists rescue neuronal dysfunction induced by Parkinson’s patient brain‐derived α‐synuclein (Click here to read more about this and click here to read the press release).

  • A new biorxiv manuscript explores PIKfyve inhibition in models of Parkinson’s; from genome-wide CRISPR screen, they find inhibiting PIKfyve reduced α-synuclein aggregation induced with fibrils from MSA patient brain (Click here to read more about this).
  • Researchers report significant enrichment of Parkinson’s risk heritability in open chromatin regions of microglia & monocytes; Microglial dysregulation as a contributing etiological factor? (Click here to read more about this).
  • FDA-approved lipid-lowering gemfibrozil reported to protects dopamine neurons in a mouse MPTP model of Parkinson’s (via PPARα-dependent astrocytic GDNF pathway); no effect in mice lacking GDNF in astrocytes (Gdnf Δastro – click here to read more about this).
  • New biorxiv manuscript from Stellate Therapeutics researchers presenting the effect of chemically synthesized queuine, STL-101 (microbiome-derived nucleobase); significantly decreases hyper-phosphorylated alpha-synuclein in model of Parkinson’s. Interesting to note that while there was no significant trend over age, there were significantly higher levels of queuine in the plasma of women compared to men (remember: higher incidence of Parkinson’s in males – Click here to read more about this).

Clinical research

  • New research provides further support for beta-synuclein in cerebrospinal fluid as an early diagnostic marker of Alzheimer’s (Click here to read more about this).
  • New research indicates that cholinergic basal forebrain volumes predicts gait decline in Parkinson’s (Click here to read more about this).
  • A study of “the Swedish National March Cohort” (44K men & women; 18–94yrs; followed 1997-2016) suggests dietary vitamin E & C intake might be inversely associated with the risk of Parkinson’s; No association found with beta-carotene or NEAC (Click here to read more about this).
  • Could low amyloid-β deposition & reduced dopaminergic activity be biomarkers for individuals with mild cognitive impairment who are at risk of dementia with Lewy bodies? New data suggests yes (Click here to read more about this).
  • False negatives in Parkinson’s-associated GBA1 sequencing (due to polymerase dependent allelic imbalance). “Both for counseling purposes & for adequate enrollment in upcoming clinical trials, a reliable sequencing method is essential” (Click here to read more about this).

  • Dynamic contrast enhanced MRI data collected from 49 individuals with Parkinson’s, 15 subjects with cerebrovascular disease, & 31 control subjects indicates subtle blood brain barrier disruption in PD (Click here to read more about this).
  • Researchers propose the “Lewy pathology consensus criteria” (LPC) to deal with low inter-rater reliability &/or an inability to unequivocally classify all postmortem cases with Lewy pathology, like Parkinson’s (Click here to read more about this).
  • Researchers report some microbially derived toxic bile acids are elevated in individuals with Parkinson’s, suggesting biliary abnormalities may play a role in PD pathogenesis – providing further support for the UDCA “UP” study (Click here to read more about this).
  • Do personality dimensions change in parallel with the development of motor fluctuations in Parkinson’s? If so, is it a consequence of the evolution of the condition? How do you even measure personality dimensions??? (Click here to read more about this).
  • New report identifies drug targets for neurological conditions (via genetics & brain transcriptomics); GRN (again!) for Parkinson’s; MR analysis points towards GPNMB inhibitors (Click here to read more about this).
  • Evaluation of the detection of GBA missense mutations and other variants using the Oxford Nanopore MinION (Click here to read more about this).

  • A charming title: “The TCR [T cell receptor] repertoire of α-synuclein-specific T cells in Parkinson’s disease is surprisingly diverse” – The first characterisation of α-syn-specific TCR clonotypes in individuals with PD (Click here to read more about this).
  • Researchers examined association between irritable bowel syndrome & Parkinson’s risk using two large databases (‘nationwide health and population registers’ & ‘Swedish Twin Registry’) & found higher PD risk both ≥5 and ≥10 years after IBS diagnosis only in the former (Click here to read more about this).
  • New report demonstrates that objective measures of freezing in Parkinson’s (using inertial sensors on the feet) in the laboratory match well with clinical scores, but unsupervised home monitoring still remains challenging (Click here to read more about this).
  • Plasma-borne indicators of inflammasome activity in Parkinson’s. Researchers present a patient-based study proposing pyroptosis as a detectable feature of PD; + potential histopath/stratification biomarkers (Click here to read more about this).

  • Could measuring levels of serum aluminum, calcium, copper, & magnesium levels in combination with gene expression analysis be a feasible diagnostic approach for Parkinson’s? (Click here to read more about this).
  • A Biogen supported analysis of biochemical markers for severity & risk in individuals with Parkinson’s-associated GBA & LRRK2 variants finds sub-clinical renal impairment is associated with increased likelihood for prodromal PD (Click here to read more about this).
  • New report provides evidence of different molecular signatures in CD 4 + T cells from individuals with Parkinson’s with & without motor complications, proposing their potential use as biomarkers of motor complications development (STAT1 & NR4A2 – Click here to read more about this).
  • Researchers performed analysis of Parkinson’s-related genes in REM sleep Behaviour Disorder, and identified potential roles for BST1 and LAMP3 (Click here to read more about this).
  • A geroscience approach for Parkinson’s Disease: conceptual framework and design of PROPAG-AGEING project (Click here to read more about this).
  • Interesting collaboration between researchers from Germany & Pakistan highlights putative second hit rare genetic variants (in HSP70 chaperone DNAJB6 & the lysosomal gene PSAP) in families with seemingly GBA-associated Parkinson’s (Click here to read more about this).
  • Characteristic of individuals with Parkinson’s who contract severe COVID-19: a study of 10 cases from Wuhan (Click here to read more about this).

  • New report showcases the potential of similarity network fusion for combining multimodal data in heterogeneous patient populations, such as the “average” person with Parkinson’s (Click here to read more about this).
  • New report finds that small fiber neuropathy does not appear to be associated with restless legs syndrome in Parkinson’s. Furthermore, no association was found between restless legs syndrome in PD and large fiber neuropathy (Click here to read more about this).
  • Using big-data, researchers analyzed large amounts of Parkinson’s symptoms mentioned in dialogues “available” from social media platforms in 2016 to 2018 to explore nocturnal symptoms in PD (Click here to read more about this).
  • New medrxiv manuscript presents quality control metrics for whole blood transcriptome analysis from the Michael J Fox Foundation Parkinson’s Progression Markers Initiative (PPMI study – Click here to read more about this).
  • New biorxiv manuscript suggests decoupling between global brain activity & associated cerebrospinal fluid flow is related to Parkinson’s cognitive impairment (Click here to read more about this).
  • Further evidence suggesting that the “Mediterranean diet” (or the Mediterranean‐DASH Intervention for Neurodegenerative Delay (MIND) diet) may be associated with delayed onset of Parkinson’s (Click here to read more about this and click here to read the press release).

  • By combining molecular imaging & fMRI, researchers report a tight link between functional activation & synaptic changes (at the molecular level), reflecting network reorganization in the Parkinson’s brain (Click here to read more about this).
  • Majority of Parkinson’s GWAS loci examined in prefrontal cortex tissue from patients (& controls) have allele-specific expression effects, emphasizing the importance of investigating variation in cis-regulation of gene expression in disease-relevant tissue (Click here to read more about this).
  • New report finds no evidence to support a role for LIN28A as a major causal gene for Parkinson’s in large European cohorts (Click here to read more about this).
  • Comparison of three motor subtype classifications in 256 individuals with de novo Parkinson’s (Click here to read more about this).
  • Three European pop.-based studies followed 528 individuals with Parkinson’s from diagnosis; 7 year results find that GBA variants are linked to a more aggressive motor progression (Click here to read more about this).
  • How do you measure “grit”? A survey of 101 members of online Parkinson’s support groups indicates that individuals with higher grit levels had higher emotional coping responses post diagnosis, exercised more, & were more willing to self-advocate (Click here to read more about this).

  • Aim: Correlate Parkinson’s neuropsychiatric symptoms (depression, psychosis, anxiety) with severity of neuropathology in nigra & locus coeruleus. Method: 175 PD brains analysed. Results: No neuropsychiatric symptoms were associated with Lewy body score (Click here to read more about this).
  • Researchers report organisational & neuromodulatory underpinnings of structural-functional connectivity decoupling in individuals with Parkinson’s; 5HT, AChR & NE transmission decoupling relates to visual dysfunction (Click here to read more about this).
  • Fine-mapping of the non-coding variation driving the caucasian LRRK2 GWAS signal across a discovery & replication Parkinson’s cohorts identifies candidate variants for further evaluation (Click here to read more about this).
  • Researchers explore the “longevity gene” Klotho & its CSF protein profiles in Parkinson’s; PD patients with KL‐VS haplotype had shorter interval btwn PD onset & cog impairment onset; plus higher UPDRS 3 scores; CSF protein levels lower in PD (vs controls – Click here to read more about this).
  • Mindfulness in Parkinson’s: Researchers report stress worsens both motor & non-motor symptoms, & they find that mindfulness may improve symptom severity, with the strongest effects on anxiety & depressed mood (survey: n=5000 PD – Click here to read more about this).

  • Using Medicare data, researchers report risk of Parkinson’s is inversely associated with herpes simplex (OR 0.79, 95% CI 0.74–0.84), herpes zoster (OR 0.88, 95% CI 0.85–0.91), & anti-herpetic medications (OR 0.87, 95% CI 0.80–0.96 – Click here to read more about this).
  • What symptoms matter most to people with Parkinson’s? New report from Parkinson’s UK suggests that the priorities of people affected by PD for improving life are personal & change with duration of the condition (Click here to read more about this).
  • A case report of immune checkpoint inhibitor treatment (nivolumab & limumab) being associated with onset of parkinsonism in 74 yr old gentleman during therapy for metastatic melanoma (Click here to read more about this).
  • New data from South Korean indicates gastric cancer patients who underwent gastrectomy & received uninterrupted VitB12 supplementation had a decreased incidence of Parkinson’s (0.86; 95% CI 0.75–0.98); significance lost after adjusting for smoking & BMI. “Among the patients who underwent TG, their risk of PD was markedly lower when they had VitB12 supplementation after surgery (aHR 0.36; 95% CI 0.17–0.76), while the risk was higher when they did not have any (aHR 1.55; 95% CI 1.03–2.32)” (Click here to read more about this).

  • Quantification of α-synucleinopathy, neurodegeneration, astrogliosis, & microgliosis in the olfactory bulb of postmortem cases of Parkinson’s finds neurodegeneration & microgliosis differences only present in males (Click here to read more about this).
  • New medrxiv manuscript highlights issues & considerations with smartphone-based digital biomarker assessments for differentiating Parkinsons (from unaffected controls – Click here to read more about this).
  • New research indicates that the modulation of prefrontal functional networks by subthalamic nuclei- deep brainstimulation is dependent on the duration of Parkinson’s before deep brain stimulation implantation (Click here to read more about this).
  • The impact of COVID-19 & social distancing on people with Parkinson’s: a US-based survey study from the Parkinson’s Foundation; 46% of PwPD would like to continue using telehealth after COVID-19 is resolved (Click here to read more about this and click here for the press summary).
  • A new biorxiv manuscript analyses 2 large datasets & finds an overabundance of opportunistic pathogens in the Parkinson’s gut that may be influenced by the host genotype; associated variants modulate a-synuclein expression (Click here to read more about this).

  • Inflammation & regulatory T cell genes are differentially expressed in peripheral blood mononuclear cells of individuals with Parkinson’s; “Increased CD49d+ Treg ratios might signify the effort of the immune system to suppress ongoing neuroinflammation” (Click here to read more about this).
  • Remote assessment of Parkinson’s symptom severity using the simulated cellular mobile telephone network (Click here to read more about this).
  • Can we see, types of Parkinson’s in pee? Researchers report urinary proteome profiling for stratifying patients with familial PD; sig. diff.s btwn PD patients & unaffected controls, plus btwn LRRK2-G2019S carriers & non‐carriers (Click here to read more about this).
  • New metabolic profiling study in Parkinson’s (using liquid chromatography-mass spectrometry) highlights metabolic disturbances in PUFA metabolism, bile acids & steroid hormone biosynthesis, caffeine & amino acid metabolism as crucial metabolic events (Click here to read more about this).
  • Rare situation, but important topic: Pregenancy with Young Onset Parkinson’s. A case report of a Chinese woman with compound heterozygous PINK1-associated juvenile Parkinson’s going through pregnancy; she delivered a healthy boy without complications; managed symptoms throughout with levodopa/benserazide (Click here to read more about this).

  • Brain imaging study (rubidium-82 PET) reveals no significant changes in blood brain barrier permeability in individuals with Parkinson’s (with or without dyskinesias – Click here to read more about this).
  • The background information regarding the PD-K2 study: A theranostic pilot study – involving a placebo-controlled parallel group design – will explore the use of Vitamin K2 in individuals with Parkinson’s & mitochondrial dysfunction (Click here to read more about this).
  • Researchers report non-invasive suppression of essential tremor (via phase-locked disruption of its temporal coherence); reduction of symptoms lasted during stimulation & for a short period afterwards in 11 individuals (Click here to read more about this).
  • Serum uric acid levels found to be lower in individuals with Parkinson’s – particularly those carrying GBA1 variants – when compared to unaffected controls; Longitudinal 2-yr data from the PPMI study, 369 de novo PD cases & 195 controls (Click here to read more about this).

New clinical trials

  • New clinical trial registered: Spanish researchers will study the feasibility & efficacy of WhatsApp as an adjunctive clinical tool for a Parkinson’s clinic (Click here to read more about this).

  • New clinical study registered: The Synuclein-One Study will be evaluating α-synuclein in individuals with Parkinson’s, Multiple System Atrophy MSA, Dementia with Lewy bodies, & Pure Autonomic Failure; recruiting 500 participants (Click here to read more about this).
  • New clinical trial registered: Exploring the effects of the “psychobiotic” Lactobacillus Plantarum PS128 on Parkinsonian symptoms; recruiting 130 participants; reporting in June 2023 (Click here to read more about this).
  • New clinical trial registered: A similar clinical trial to the one above has also been registered to look at the “psychobiotic” Lactobacillus Plantarum PS128 in a cohort of 20 individuals with early onset Parkinson’s; 12 week study; completing end of 2021 (Click here to read more about this).
  • In a new study, researchers are looking for participants to take part in a research project on how feelings of control & mood in people with Parkinson’s may affect taking medication. Have a look & consider completing their quick survey (Click here to read more about this).
  • New clinical trial registered: Evaluation of the safety & effectiveness of bilateral ablation of the pallidothalamic tract for the treatment of the motor complications of Parkinson’s; Insightec are seeking 50 individuals for this experimental Magnetic Resonance-guided Focused Ultrasound study (Click here to read more about this).

Clinical trial news

  • An open label, dose-escalating study of safety & tolerability of cannabidiol in 13 individuals with Parkinson’s; CBD “may be efficacious in PD, but the relatively high dose used in this study was associated with liver enzyme elevations” (Click here to read more about this).
  • Eli Lilly‘s Donanemab (recognizes Aβ(p3-42)) slows clinical decline in Phase II Alzheimer’s trial; met primary (iADRS), slowing decline by 32% (vs placebo); consistent improvements in all prespecified secondary endpoints (Click here to read more about this).

  • Results from a Phase 2, open-label study of Zuranolone (SAGE-217; an oral neuroactive steroid GABAA receptor PAM) as a treatment for Parkinson’s tremor finds tremor score improved by 40% (Click here to read more about this)
  • A randomised controlled trial showed that consumption of a multi-strain probiotic (Hexbio®) over 8 weeks improved bowel opening frequency and whole gut transit time in PD patients with constipation (Click here to read more about this).
  • Denali Therapeutics provided a progress report in January: Late-stage clinical development of their Parkinson’s-targeted LRRK2 inhibitor, DNL151 (BIIB122) to begin by year-end 2021, in collaboration with Biogen; 2 large trials are planned. Denali also announced 5 new brain-penetrant enzyme replacement therapy programs with their ETV technology, including ETV:GBA for Gaucher disease & Parkinson’s. Busy year ahead (clinically) for the company – interesting times for research! (Click here to read more about this)

  • New clinical trial (PaDoMi Study) results indicate that mirabegron is effective in treating overactive bladder symptoms in patients with Parkinson’s with acceptable adverse events (Click here to read more about this).
  • New report shares the results of the open-label phase of the TOLEDO study: Long-term safety & efficacy of apomorphine infusion in individuals with Parkinson’s suffering persistent motor fluctuations (Click here to read more about this).
  • Medtronic announces the first enrolment of the ADAPT-PD trial evaluating the safety & efficacy of adaptive deep brain stimulation in individuals with Parkinson’s – automated adjustment of brain stimulation (Click here to read more about this).

  • The results of a double‐blind, randomized, controlled trial of Lovastatin in 70 individuals with early‐stage Parkinson’s; Lovastatin treatment was well tolerated & “associated with a trend of less motor symptom worsening” (Click here to read more about this).
  • Researchers assessed all Parkinson’s clinical trials in the World Health Organisation trials portal (1999 – 2019); 357 trials (152 compounds); 17.3%=Phase 1, 37.8%=Phase 2, 23.8%=Phase 3 trials; 48.2% conducted on repurposing molecules; FDA regulatory approval = 21.4% of cases (Click here to read more about this).

Conferences/lectures

  • The World Parkinson’s Congress Virtual meeting on Advancing Science, Care, & Living with Parkinson’s will be held Monday – Friday 17 – 21st May. Topics presented during this five-day virtual program will include updates on: Basic Science, Clinical Science, Treatment Options, Comprehensive Care, and Living with Parkinson’s (Click here to read more about this).

Other news

  • Another very nice piece remembering Prof Oleh Hornykiewicz – both the man & his contributions to the understanding & current treatment of Parkinson’s (Click here to read more about this).
  • Inhibikase Therapeutics announces a new partnership with Clintrex Research Corporation; Prof Warren Olanow to serve as interim CMO; This “rounds out Inhibikase’s core clinical development team for development of IkT-148009 as a treatment for Parkinson’s” (Click here to read more about this).

  • RNA-editing company Shape Therapeutics is going to unveiling their AI-powered RNAfix™ high-throughput discovery platform & its application to LRRK2-related Parkinson’s at the J.P. Morgan 39th Annual Healthcare Conference (Click here to read more about this).
  • Atalanta Therapeutics: New biotech – backed by $110 from Biogen, Genentech, & F-Prime Capital – focused on sustained CNS gene silencing. Biogen gets Huntington’s disease; Genentech gets Parkinson’s & Alzheimer’s; Atalanta gets milestones & royalties (Click here to read more about this).

  • Good to see big pharma really getting into exploration of digital biomarkersBiogen initiates pioneering study to develop measures of cognitive health (using Apple Watch & iPhone – Click here to read more about this).
  • “How TikTok users designed a better pill bottle for people with Parkinson’s” (Click here to read more about this).

  • Anavex Life Sciences announces that it has been awarded a research grant (from the Michael J Fox Foundation) to investigate PET imaging biomarkers to measure target engagement of ANAVEX®2-73 (blarcamesine) for the treatment of Parkinson’s (Click here to read more about this).
  • Further funding support for Wren Therapeutics; Company announces the closing of £12.4m ($17m) financing; “Advanced lead small molecule programs targeting amyloid-β and α-synuclein, with first clinical candidate for amyloid-β in Q1 2021” (Click here to read more about this).

  • Aspen Neuroscience announces the appointment of Damien McDevitt as president & CEO, to help take their iPS cell programme forward for cell transplantation in Parkinson’s (Click here to read more about this).
  • Atuzaginstat in Parkinson’s. Biotech firm Cortexyme announces the “PEAK Trial” (Parkinson’s gingipain inhibitor Trial) has begun study start-up activities; The first patient is expected to be recruited in Q3 2021 (Click here to read more about this).

Review articles/videos

  • A critical review of the pharmacological treatment of REM sleep behavior disorder in adults. Is it time for more & larger randomized placebo-controlled trials? Interesting discussion on clonazepam & melatonin (Click here to read more about this).
  • Cholesterol metabolism in neurodegenerative conditions like Parkinson’s: Molecular mechanisms & therapeutic targets (Click here to read more about this)
  • A useful review of miR-124 in the pathogenesis of human medical conditions, like Parkinson’s (Click here to read more about this).
  • Interesting review of research suggesting acylated ghrelin as a multi-targeted therapy for Alzheimer’s & Parkinson’s (Click here to read more about this).
  • New review discusses the convergence of data around alpha-synuclein, mitochondrial, & lysosomal pathways in vulnerability of midbrain dopaminergic neurons in Parkinson’s (Click here to read more about this).
  • Interesting review on an interesting drug: Zonisamide for the treatment of Parkinson’s: An update (Click here to read more about this)

  • New review on historical perspectives of the involvement of Ferroptosis in chemically induced models of Parkinson’s (Click here to read more about this).
  • I am almost reluctant to share this one, but… Interesting discussion on venoms (yes, snake, bees, etc) as an adjunctive therapy for Parkinson’s: where are we now & where are we going? (Click here to read more about this).
  • A useful review on the role of PARP1 in aging & neurodegenerative conditions, like Parkinson’s (Click here to read more about this).
  • Interesting short review on Parkinson’s-associated alpha-synuclein, exploring interplay of pathology, neuroinflammation, & environmental factors (Click here to read more about this).
  • A useful review on Parkin function & Parkinson’s; can the stimulation of normal activity of Parkin potentially ameliorate the dysfunctions observed in PD? (Click here to read more about this).
  • Microglial turnover in ageing-related neurodegeneration – a review exploring research on microglial function & senescence in conditions like Parkinson’s (Click here to read more about this).

  • Interesting review introducing novel endogenous & synthetic Nurr1 agonists, & discusses their potential effects in Nurr1-related conditions, like Parkinson’s (Click here to read more about this).
  • Fascinating review – Lipids, lysosomes & mitochondria: insights into Parkinson’s-associated Lewy body formation from rare monogenic disorders (Click here to read more about this).
  • Interesting perspective: “30 yrs of research on autonomic dysfunction, non-motor features, & endophenotypes in Parkinson’s”; “A shining example of how researching the relatively unknown can lead to better treatment” (Click here to read more about this).
  • Celebrating 10 years of Journal of Parkinson’s – noting special features of the journal such as “Clinical Trial Highlights” and the quarterly webinars (Click here to read more about this).
  • Crossing the “Valley of Death” – key considerations regarding regenerative medicine using iPS cells for Parkinson’s: scientific rationale, pre-clinical study, & the kyoto clinical trial – from the man, the myth, the legend: Prof Jun Takahashi (Click here to read more about this).

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

And there it is, just some of the highlights from January 2021 – 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 February!!!

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You can do whatever you like with it!


EDITOR’S NOTE:  The author of this post is an employee of the Cure Parkinson’s Trust, so he might be a little bit biased in his views on research and clinical trials supported by the trust. That said, the trust has not requested the production of this post, and the author is sharing it simply because it may be of interest to the Parkinson’s community.

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.


One thought on “Monthly Research Review – January 2021

  1. Interesting to read about the doxycycline, I don’t know what’s happening to my alpha synuclein inclusions but I am still on doxy some 5 years after diagnosis (and 4 years prior) and my symptoms are still very sow progressing.

    Like

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