Monthly Research Review: Jaunary 2020

 

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 January 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, and Review articles/videos

 


So, what happened during January 2020?

In world news:

January 6th – From the only in London files – this was “No Trousers Tube Ride 2020” day (don’t ask me to explain… I wouldn’t know where to begin – click here to read more about this).

January 23rd – The Chinese city of Wuhan was placed under quarantine, in which all public transport in and out of the city was suspended in efforts to control the spread of a new coronavirus, designated 2019-nCoV.

January 26th – In the build up to BREXIT, the UK presented the new 50 pence coin… with a gramatical error. Three million coins bearing the slogan “Peace, prosperity and friendship with all nations” are due to enter circulation from 31 January (Click here to read more about this).

January 30th – The Daniel K Inouye Solar Telescope on Hawaii released new footage of the surface of the sun showing features as small as 30km across.(Click here to read more about this).

 

31st January – As the bush fires in Australia have continued over January, a state of emergency was declared in the Canberra region, with fires reaching suburbs just south of the capital (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 2020, there were 849 research articles added to the Pubmed website with the tag word “Parkinson’s” attached (8195 for all of 2019 – updated number). 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. Immune system:

The results of the Ambrxol clinical trial in Parkinson’s (supported by The Cure Parkinson’s Trust, Van Andel Institute, & John Black Charitable Foundation). The drug was found to be safe and well tolerated at the doses used, it also accessed the brain and raised levels of the target protein, glucocerebrosidase ( to read more about this study, click here for the summary and click here to read a SoPD post about this topic)

 

2.  Dormant dopamine neurons

Researchers in Korea reported that in the postmortem Parkinsonian brain there are a significant portion of “dormant dopamine neurons”. Rather than immediately dying, the investigators found that dopamine neurons in the substantia nigra region of the brain simply stop producing the neurotransmitter dopamine. They found that in both mild & severe Parkinson’s brains, dormant dopamine neurons could account for 54.7% & 27.0% of the dopamine neurons, respectively – raising the possibility that “dormant but recoverable” dopamine neurons are still alive in the brain in Parkinson’s ( to read more about this, click here to read the press release, and click here to read a SoPD post on this study).

 

3. Food for worms?

Researchers in Scotland reported that the probiotic Bacillus subtilis protects against Parkinson’s-associated α-synuclein aggregation in microscopic roundworms (C. elegans), by changing the host sphingolipid metabolism ( to read more about this, click here for a press summary, click here for the Parkinson’s UK summary, and click here to read a SoPD post on this topic).

4. Natural killers

Natural killer cells are innate effector lymphocytes that are present in the brain. Researchers report human NK cells can efficiently internalise & degrade Parkinson’s-associated α-syn aggregates. In vivo NKC depletion exacerbated PD model ( to read more about this and click here to read a SoPD post on this topic).

 

5. Get ready to ROCK?

Researchers conducted a screen of ~3000 compound to identify small molecules that increase PARKIN recruitment to damaged mitochondria & ensuing mitophagy. Rho-associated protein kinase (ROCK) inhibitors highighted & rescue models of Parkinson’s. The identified ROCK inhibitor SR3677 has poor bioavailablity, but the authors suggested Fasudil could be a more agreeable ROCK inhibitor for repurposing for Parkinson’s & present data supporting it ( to read more about this).

6.  PEP005 the PKC agonist

Researchers in California generated induced pluripotent stem cells from individuals with young onset Parkinson’s (diagnosed under the age of 40 years). None of the individuals carried any known genetic risk factors for PD. The researchers grew dopamine neurons which showed accumulation of α-synuclein protein, which could rescued by the PKC agonist PEP005. PEP005 delivery into the striatum region of the mouse brain also decreased α-synuclein levels ( to read more about this and click here to read the press release).

 

Basic biology news

  • Researchers have a bioRxiv manuscript suggesting 2 C-terminal sequence variations determine differential neurotoxicity between human & mouse α-synuclein ( to read more about this).
  • Researchers conducted transcriptomics & quantitative proteomics studies to find common & distinct Parkinson’s pathways from PARKIN, DJ-1, or ATP13A2 knockout dopamine neurons. Mitochondrial & lysosomal dysregulation found in all of the lines ( to read more about this).
  • Vps35 is a risk factor for neurodegenerative conditions like Parkinson’s & Alzheimer’s. Now researchers reveal an association of axon/dendrite terminal differentiation deficit with neurodegenerative pathology (including lysosomal involvement – to read more about this).
  • Researchers have a bioRxiv manuscript suggesting that Parkinson’s-associated LRRK2 mutations reshapes synaptic structure & function of striatal excitatory synapses ( to read more about this).

  • Synaptotagmin‐11 (Syt11) has been associated with Parkinson’s. Now researchers report Syt11 stabilizes caveolar structures (involved in intracellular membrane trafficking) in astrocytes & regulates their function in physiological & pathological conditions ( to read more about this).
  • Researchers have a bioRxiv manuscript suggesting that heat shock response is NOT induced by treatment with aggregated forms of Parkinson’s-associated a-syn or ALS-associated SOD1G93A. The “results suggest that pathogenic proteins either evade detection or impair induction of the HSR in neuronal-like cells” ( to read more about this).
  • Researchers have a bioRxiv manuscript suggesting that conformation of Parkinson’s-associated LRRK2’s kinase domain regulates its microtubule interaction; closed conformation favoring binding. Implications for LRRK2 inhibitor design ( to read more about this).
  • Researchers have a bioRxiv manuscript in which they present a multi-omic atlas of the human brain via profiling of single-cell chromatin accessibility, expanding our understanding of inherited variation in Alzheimer’s & Parkinson’s ( to read more about this).
  • Researchers report that the unfolded protein response generates a distinct reactivity state in astrocytes, & targeting PERK-eIF2α signaling in these astrocytes is neuroprotective (in prion disease mice models – to read more about this).
  • Photonic Pharma researchers have a bioRxiv manuscript presenting a high-throughput, FRET-based drug discovery platform for identifying compounds that protect against Parkinson’s-associated a-synuclein aggregation & toxicity ( to read more about this).

  • Loss of Parkinson’s-associated PARKIN function (in mice) leads to amplifications of synchronized cortico-striatal oscillations & an intrastriatal reconfiguration of interneuronal circuits. May precede nigro-striatal neurodegeneration ( to read more about this).
  • Researchers report the capacity of a small molecule (ZPD-2), identified after a high-throughput screening, to inhibit Parkinson’s-associated α-synuclein aggregation (in vitro & 2x c. elegans PD models – to read more about this).
  • Researchers report a simple, versatile & robust centrifugation‐based filtration protocol for the isolation & quantification of Parkinson’s-associated α‐synuclein monomers, oligomers & fibrils ( to read more about this).
  • Researchers report that ondansetron – a highly selective 5-HT3 receptor antagonist – reduces L-DOPA-induced dyskinesia in the 6-OHDA-lesioned rat model of Parkinson’s (Click here to read more about this).
  • Researchers have a bioRxiv manuscript proposing an experimental & theoretical approach for elucidating the molecular pathways driving the dynamics of oligomers during ongoing aggregation of Alzheimer’s-asssociated β-amyloid. They suggest that only a minority of β-amyloid42 oligomers actually convert into fibrillar species. Could the same apply to Parkinson’s-associated alpha synuclein? ( to read more about this).
  • Researchers report that N-terminal acetylation of Parkinson’s-associated α-synuclein changes the affinity for lipid membranes but not the structural properties of the bound state ( to read more about this).

  • Researchers present a multi-omic analysis of growth cones at different stages during development which provides insight into adult neuro-regeneration pathways (optic nerve data –  to read more about this).
  • Researchers report a “viable chaperone-based strategy for reversing the synaptic vesicle trafficking defects associated with excess α-synuclein, which may be of value for improving synaptic function in Parkinson’s” ( to read more about this).
  • Researchers researchers report that LINGO1 is a regulator of large conductance calcium-activated potassium channels, which causes a “functional knockdown” of these currents & may contribute to the tremor associated with increased LINGO1 levels. LINGO1 is a transmembrane protein that is reported to be up-regulated in the cerebellum of patients with Parkinson’s & Essential Tremor. Patients with additional copies of the LINGO1 gene also present with tremor ( to read more about this and click here for a media summary).
  • Researchers have a manuscript on bioRxiv suggesting that neurodegeneration caused by the Parkinson’s-associated LRRK2 G2019S mutation is highly influenced by dietary amino acid levels in adult Drosophila & in mammalian neuron cultures ( to read more about this).
  • Researchers present a PPDA-derivative (UBP791) to enable more precise investigation of NMDAR activity. New tool for Parkinson’s research ( to read more about this and click here to read the press release, and oh look – a video explaining it all too:

  • Researchers have a bioRxiv manuscript suggesting that Parkinson’s-associated LRRK2 recruits JIP4 to lysosomes, where it promotes formation of LAMP1-negative lysosomal tubules that release membranous content from ruptured lysosomes. They describe a novel, LRRK2-orchestrated process involving lysosomal tubulation to release vesicular structures from permeabilized lysosomes, which they call “LYTL” (LYsosomal Tubulation/sorting driven by LRRK2). Interesting given the central role of lysosomes in Parkinson’s ( to read more about this).
  • Researchers report that high-salt diet does not aggravate neuroinflammation or neurodegeneration in mouse model (PLP-hαSyn) of multiple system atrophy (MSA). Cytokines, chemokines, T cell recruitment & astrogliosis were unaffected ( to read more about this).
  • Researchers present a molecular mode of action for derailment of protein-protein interaction by neurotoxic fibrils. They show that π-stacking by Arginine side-chains drives protein binding to Tau fibrils. Hsp90 modulates aberrant fibril binding ( to read more about this).
  • Researchers investigate the role of a post-translational modification, N-terminal acetylation, on the neurotoxicity of Parkinson’s-associated alpha synuclein. They report N-terminus determines (most likely via acetylation) protein levels & toxicity ( to read more about this).
  • Researchers have a bioRxiv manuscript suggesting a role for intra-mitochondrial protein homeostasis in Parkinson’s-associated alpha synuclein fibril elongation. Interference (via intra-mitochondrial proteases) aggravates aggregation ( to read more about).

  • Researchers establish Parkinson’s-associated ATP13A2 (PARK9) as a lysosomal polyamine exporter that shows the highest affinity for spermine among the polyamines examined. Defective export may be a mechanism for lysosome-dependent cell death ( to read more about this and click here to read the press release).
  • Researchers have a bioRxiv manuscript presenting the “Atlas of Inflammation-Resolution” (AIR) – a web-based resource for acute inflammation & inflammation resolution research ( to read more about this).
  • WHOA! In vivo genome-wide genetic screening in the mammalian brain! Researchers created a genome-wide genetic screen in the mouse brain & identified new targets for Huntington’s disease. Powerful stuff! ( to read more about this).
  • New word for me: Macropinocytosis It is a specialized form of endocytosis in macrophages. Researchers have a bioRxiv manuscript suggesting Rab10 is a primary effector of macropinocytosis, & Parkinson’s-associated LRRK2 is involved ( to read more about this).
  • Translation of the intrinsically disordered protein α-synuclein is inhibited by a small molecule (“Synucleozid“) which targets its structured mRNA (Click here to read more about this and click here to read the press release).

 

Disease mechanism

  • Researchers report that glutathione derivative CR-777 increased cell survival and neurite network and decreased the expression of α-synuclein in 6-OHDA model of Parkinson’s (via the PI3K/mTOR pathway – to read more about this).
  • Researchers report that DJ-1-binding “compound B” stimulated oxidative stress-induced transcriptional activity of Nrf2 in Parkinson’s model. Compound B strongly increased Nrf2 activity even in Keap1-mutant A549 cells (Click here to read more about this).
  • A meta analysis suggests that reductions in copper levels and elevations in iron are characteristics of the degenerating substantia nigra in Parkinson’s (Click here to read more about this).
  • Olive oil again! Researchers report that hydroxytyrosol – derived from extra virgin olive oil – is able to reduce the inflammation induced by two different stimuli: lipopolysaccharide & Parkinson’s-associated α-synuclein (in vitro – to read more about this).

  • Researchers led a consortium to perform a high-content imaging-based assay of Parkinson’s-associated PARKIN recruitment to mitochondria & screened large druggable libraries to identify modulators of PARKIN (hello kenpaullone – to read more about this).
  • Researchers report granzyme-positive CD8 T blood cells next to degenerating neurons in hippocampus of Alzheimer’s brains. A smoking gun or a dead body? ( to read more about this and click here to read the press release).
  • Researchers present new ultra-stable cytoplasmic antibodies engineered for in vivo use. Useful for inhibiting in vivo transmitter release, modulating animal behaviour, & drugging the “undruggable”. Used in Parkinson’s-associated dopamine cells ( to read more about this).
  • Researchers report data on the influence of D2 & D3 dopaminergic signalling in hypomania & saccadic changes in Parkinson’s, & suggest that saccadic performance is associated with the clinical psychiatric state ( to read more about this).
  • New data reporting that a dual GLP-1/GIP receptor agonist (called DA-CH5) is superior to just a single GLP-1 receptor agonist (liraglutide) in a MPTP model of Parkinson’s ( to read more about this).
  • Further research suggesting that incretins glucagon-like peptide-1 (GLP-1) & glucose-dependent insulinotropic polypeptide (GIP) could have useful neuroprotective properties. This time in models of traumatic brain injury. Liraglutide vs twincretin (Click here to read more about this).
  • Alzheimer’s-associated beta-amyloid plaques promote seeding and spreading of alpha-synuclein and tau in a mouse model of Lewy Body disorders with Aβ pathology (Click here to read more about this).
  • Aptinyx Inc report new preclinical data for their NMDAR modulator NYX‐458 as a potential therapeutic for cognitive decline in Parkinson’s ( to read more about this).

  • Researchers use DREADD activation of pedunculopontine cholinergic neurons to reverses motor deficits (& restores striatal dopamine signaling) in a rodent model of Parkinson’s. Implications for refining PPN-deep brain stimulation ( to read more about this).
  • Researchers report that complement receptor 4, part of the innate immune system, selectively binds to Parkinson’s-associated fibrillar α-syn, but not monomeric species. And clearance of fibrillar α-syn is dependent on receptor conformation (Click here to read more about this).
  • Pharmacological inhibition of colony stimulating factor‐1 receptor (CSF1R) by cFMS kinase inhibitor GW2580 reduces microglial proliferation & is protective against neuroinflammation & neurodegeneration in models of Parkinson’s ( to read more about this).
  • Researchers have a bioRxiv manuscript suggesting the coagulation & complement (essential branch of the innate immune system) cascades may contribute to alpha-synuclein-induced neurodegeneration associated with Parkinson’s ( to read more about this).
  • Researchers suggest that increasing SIRT3 levels can counteract Parkinson’s-associated α-synuclein-induced mitochondrial dysfunction, by reducing α-synuclein oligomers & normalizing mitochondrial bioenergetics. AICAR restores SIRT3 ( to read more about this).
  • Researchers report antihypertensive agent Hydralazine exhibits protective properties on a cellular model of Parkinson’s, by increasing antioxidant capacity via HIF-1α ( to read more about this).
  • Researchers report that subthalamic deep brain stimulation in Parkinson’s model improved motor impairment, induced astrocytic hyperplasia, & reduced inflammatory markers ( to read more about this).

  • Researchers present a new purine derivative drug called PDD005, which targets Prohibitin. PDD005 treatment reduced neuro-inflammation (decreasing activation of astrocytes & microglia) & rescued cognitive deficit in aging mice ( to read more about this).
  • Does NF-κB c-Rel subunit have a prosurvival/anti-inflammatory role in Parkinson’s? c-Rel inhibitor IT901 aggravates MPTP-induced damage in PD model ( to read more about this).
  • Researchers have a bioRxiv manuscript exploring biomarkers markers of LRRK2 inhibition in multiple biofluids from non-human primates. Useful for Parkinson’s LRRK2 clinical trials ( to read more about this).
  • Researchers report that T cell priming & infiltration into the CNS are key mechanisms of disease pathogenesis in Multiple Systems Atrophy (MSA – to read more about this).
  • Researchers report that fibroblast mitochondria from cases of idiopathic Parkinson’s display morphological changes & enhanced resistance to depolarization. Q: If PD is a neurodegenerative condition, why are skin cells so affected? ( to read more about this).
  • Researchers explored extracellular vesicles (EVs) from cerebrospinal fluid of 7 people with Parkinson’s (vs control samples). Their results suggest that subpopulations of EVs with different & specific functions may exist ( to read more about this).

 

Clinical research

  • A multi-centre retrospective study of dementia in long-term (20+ yrs) Parkinson’s finds 36 of 2327 cases had duration over 20yrs+ & only 7 (19%) were classified as probable PD dementia (Click here to read more about this).
  • Further reason to be active! ARTFL/LEFFTDS Study researchers report “Active lifestyles were associated with less functional decline & moderated brain-to-behavior relationships longitudinally” in the context of frontotemporal lobar degeneration (FTLD) ( to read more about this).
  • Researchers provide further evidence of NLRP3 inflammasome activation in the blood cells in Parkinson’s. Plus, IL-1β & α-synuclein in plasma were increased in PD (vs controls), & both presented a positive correlation with motor severity ( to read more about this).

  • Researchers report younger cases of Parkinson’s have lower intraventricular temperature in their brains (vs controls; no diff in older cases). Brain temperature positive correlations with inflammatory markers (eg plasma nuclear DNA & L-selectin – to read more about this).
  • Researchers report abnormal peripheral blood lymphocyte subpopulations have clinical relevance for Parkinson’s ( to read more about this).
  • Researchers have a bioRxiv manuscript presenting a microbiome-wide association study on 2 large Parkinson’s datasets, suggesting novel associations with commensal microorganisms which can become opportunistic pathogens ( to read more about this).
  • Researchers report on the development of digital biomarkers for resting tremor & bradykinesia in Parkinson’s using a wrist-worn wearable device ( to read more about this).
  • Results from project BlueSky! Researchers highlights significant opportunity for objective, high-res, & continuous monitoring using wearable technology to monitor Parkinson’s symptoms ( to read more about this, and click here to read a previous SoPD post on this project).
  • A second manuscript from the “smell of Parkinson’s” study has been made available pre-print on chemRxiv (Click here to read more about this).

  • Researchers have a bioRxiv manuscript describing the use of crowdsourcing to evaluate & benchmark features derived from accelerometer & gyroscope data in 2 different datasets to predict presence of Parkinson’s & severity of 3 features ( to read more about this).
  • Researchers provide the first evidence of synaptic loss in brainstem nuclei involved in the pathogenesis of Parkinson’s in living patients using synaptic vesicle glycoprotein 2A (SV2A) imaging. PD group exhibited lower SV2A in the nigra (Click here to read more about this).
  • Researchers analysed cerebrospinal fluid from Parkinson’s, multiple system atrophy (MSA), vascular parkinsonism & controls using PEA (multiplex proximity extension assay). MCP-1 & MMP-10 correlated with PD progression ( to read more about this).
  • Researchers present “Tremoroton” (love the name!) – a new free online platform for tremor analysis in conditions like Parkinson’s. Up to 6 channels; assessing time, frequency, time-frequency analysis & calculate coherence ( to read more about this).
  • Researchers from the Michael J Fox Foundation “Fox Insight study” collected data online from individuals with self-reported Parkinson’s & compared it to traditional (in-person) observational studies. Proportion of females sig. higher, but similar responses overall ( to read more about this).

  • Researchers report that decreases in Valosin-containing human protein (VCP or p97) levels might serve as a biomarker for the development of pathology at the early clinical & preclinical stages of Parkinson’s ( to read more about this).
  • Researchers use 13‐years of the CamPaIGN cohort data to suggest that motor complications in Parkinson’s are related to severity of nigrostriatal pathology rather than early levodopa use; & early complications do not = negative prognosis ( to read more about this).
  • Researchers have a medRxiv manuscript suggesting that locus coeruleus pathology in progressive supranuclear palsy (PSP; similar to Parkinson’s) correlates with tau pathology & disease severity ( to read more about this).
  • Researchers report there is a distinct pattern of association at the alpha synuclein genetic (SNCA) locus in REM sleep behaviour disorder (as compared to Parkinson’s – click here to read more about this).
  • Asymmetry in OFF-state arm swing velocity may be a useful parameter in distinguish GBA variant carriers with Parkinson’s from non-GBA carriers (Click here to read more about this).
  • Researchers present pBrain: A novel pipeline for Parkinson’s-related brain structure segmentation ( to read more about this).
  • Researchers evaluated serum levels of gamma-glutamyltransferase & found a significant association with the future development of Parkinson’s. Men with higher GGT activity had a lower risk, whereas women with higher GGT activity had a higher risk ( to read more about this).

  • Researchers have a medrxiv manuscript suggesting that they “did not find evidence to support a role for heterozygous PINK1 mutations as a risk factor for Parkinson’s” ( to read more about this).
  • Researchers provide further evidence of gastrointestinal dysfunction in Parkinson’s (Click here to read more about this).
  • A study exploring the relationship between the serum urate levels & patterns of striatal dopamine depletion in 167 patients with de novo Parkinson’s further highlights potential sex‐specific protective effect of urate (
  • In a nested case-control population-based analysis, traumatic brain injury was NOT associated with subsequent α-synucleinopathies in general or any individual α-synucleinopathy, & this did not change based on the temporality or the severity of the TBI (Click here to read more about this).
  • A study from Russia suggesting a correlation between radiation exposure and Parkinson’s relative risk (Click here to read more about this).
  • Researchers present a whole exome sequencing study of Parkinson’s & related conditions in the Italian population ( to read more about this).

  • Researchers present an analysis of neurodegenerative disease-causing genes in dementia with Lewy bodies (DLB). Conclusion: “mutations in genes known to cause other neurodegenerative diseases are not a common cause of DLB” (Click here to read more about this).
  • Wow – non-invasive recording from the human olfactory bulb. Could this be a new tool for Parkinson’s research? ( to read more about this).

 

 

New clinical trials

  • New clinical study registered: the “LRRK2 International Parkinson’s Disease Study” (LIPAD) study. Seeking to recruit 4000 participants (Click here to read more about this and click here to read a SoPD post on this study)
  • New Phase II clinical trial registered in South Korea evaluating multiple doses of herbal extract WIN-1001X in 188 people with Parkinson’s. 12 weeks treatment; 1st endpoint=MDS-UPDRS Part 3; completes late 2020 (Click here to read more about this study).
  • Phase I trial of Alector‘s treatment AL101 for the treatment of neurodegenerative conditions has been registered. This is a monoclonal antibody designed to increase progranulin levels. Trial to enroll up to 42 healthy volunteers (click here to read more about the trial).
  • The CHIEF PD (CHolinesterase Inhibitor to prEvent Falls in Parkinson’s Disease) study is now registered. Phase III trial, recruiting 600 people with Parkinson’s, Rivastigmine transdermal patches for up to 12 months (Click here to read more about this).

  • Researchers are recruiting 30 people with Parkinson’s, 30 with Alzheimer’s/Mild Cognitive Impairment, & 60 age-matched controls; 2 visits (questionaire & blood samples); exploring autoimmunity in neurodegenerative conditions (Click here to read more about this).
  • New clinical study registered to explore Nordic walking exercise on gait, motor/non-motor symptoms, & exercise biomarkers in Parkinson’s (Click here to read more about this).
  • New clinical trial registered to explore the use of wearable & mobile data to diagnose & monitor movement disorders, including Parkinson’s (Click here to read more about this).
  • The “Exenatide-PD3” Phase III trial of exenatide Parkinson’s being conducted in the UK; 96 weeks of treatment/placebo in 200 participants, finishes Sept 2023 (Click here to read more about this).

  • New clinical study registered: A brain imaging study assess synaptic density in 30 people with Parkinson’s (vs 20 controls – click here to read more about this).
  • “SMELLPARK” is exploring the role of nasal dysbiosis in Parkinson’s. The study is recruiting 160 PD patients & 160 controls for nasal swabs & clinical evaluation (Click here to read more about this).

 

Clinical trial news

  • Alector has initiated their 1st-in-human Phase 1 study of AL101 for the treatment of neurodegenerative conditions, like Parkinson’s. This is a monoclonal antibody designed to increase progranulin levels. Trial to enroll up to 42 healthy volunteers ( to read more about this and click here to read more about the trial).

  • The 1st participant in the CHIEF-PD (CHolinesterase Inhibitors to prEvent Falls in Parkinson’s Disease) trial has been recruited ( to read more about this).
  • Results of Phase I clinical testing for Neuropore Therapies‘s drug NPT520-34 suggest that the drug was “safe & tolerable at all doses tested” in healthy individuals. Now on to Phase II testing in Parkinson’s & ALS ( to read more about this).

  • Neos Therapeutics has completed dosing in a Phase 1 Trial of their therapy NT0502, which they are developing for the treatment of chronic sialorrhea (excessive drooling) – a common feature in Parkinson’s ( to read more about this).
  • Axovant Therapies report 12 month data for the first 2 individuals with Parkinson’s treated with their gene therapy approach (“AXO-Lenti-PD“). Well-tolerated, no serious adverse events, & improvement in the UPDRS III “OFF” ( to read more about this).

  • Researchers report positive results from randomized clinical trial of RimabotulinumtoxinB for treatment of sialorrhea (excessive drooling) in adults (including 122 with Parkinson’s). Well tolerated & reduced sialorrhea (Click here to read more about this).
  • Denali Therapeutics announces LRRK2 inhibitor DNL201 Phase 1b trial demonstrated high levels of target & pathway engagement, including improvement of lysosomal biomarkers in patients with Parkinson’s. Final data rexpected in mid-2020 ( to read more about this).

  • Anavex Life Science has announced that it has met its enrollment target for the ANAVEX®2-73 (blarcamesine) Phase 2 clinical study in Parkinson’s Disease Dementia. The company expects to announce topline results from this study by mid-2020 ( to read more about this).
  • A (small) randomized, controlled study suggests diabetes drug Liraglutide (which is being repurposed for Parkinson’s by The Cure Parkinson’s Trust Van Andel Institute) might slow memory decline in obese patients with prediabetes or early type 2 diabetes ( to read more about this).

 

Other news

  • Medtronic has received a CE mark for its Percept PC deep brain stimulation system, that can not only deliver electrical therapy but also record the brain’s signals in order to adjust & personalise treatment for people with conditions like Parkinson’s ( to read more about this).
  • Researchers are part of a consortim that has been awarded a $4 million grant to investigate the possibility of building synthetic neurons for Parkinson’s ( to read more about this).
  • The Michael J Fox Foundation and Sage Bionetworks, launched BEAT-PD, a data challenge designed to benchmark new methods to predict on/off medication status and symptom severity in people with Parkinson’s ( to read more about this).

  • Researchers have published the protocol for the NICE-PD study, evaluating the (cost-)effectiveness of specialized nursing care provided by a Parkinson’s nurse (compared with usual care) at all disease stages ( to read more about this).
  • Seelos therapeutics is to begin preclinical testing of SLS-007 – a gene therapy approach involving rationally designed peptidic inhibitors that target the non-amyloid component core of α-synuclein to inhibit protein aggregation in Parkinson’s ( to read more about this).
  • AFFiRiS announced that the US FDA responded to its pre-IND submission for their Phase 2 trial of AFFITOPE(R) PD01 (immunotherapy) in early Parkinson’s. Study to start in the US & Europe in H2 2020 ( to read more about this).

 

 

Review articles/videos

  • A review of the findings from the different gut microbiome studies & consider the future of this research in the context of Parkinson’s. “It would be interesting to compare microbiota from Parkinson’s patients with different familial mutations: do different forms of α-syn & phenotypic presentations of PD result in specific changes to the gut environment?” (Click here to read more about this).
  • A useful overview & review of the NLRP3 inflammasome in neurodegenerative conditions like Parkinson’s ( to read more about this).
  • A review of our current knowledge of lipids in Parkinson’s & consider their role in synucleinopathies ( to read more about this).
  • An excellent discussion about exercise and Parkinson’s:

  • The future of stem cell therapies for Parkinson’s (Click here to read more about this).
  • A timely discussion of where we are & the challenges we face regarding regenerative medicine & tissue engineering strategies for Parkinson’s (The SoPD is hoping regeneration will be a theme for 2020! to read more about this).
  • Pain is one of the most common features of PD & yet least researched. Now researchers discuss the potential of animal models for advancing the understanding & treatment of pain in Parkinson’s ( to read more about this).
  • Everything you need to know about autophagy & Parkinson’s-associated LRRK2 in the aging brain (a lot of bases covered – to read more about this).
  • This short review discusses recent developments in research on Cysteamine & Cystamine to counter neurodegenerative conditions like Parkinson’s ( to read more about this).
  • Researchers have produced an interesting opinion piece: “Omics in Neurodegenerative Disease: Hope or Hype?”. They “argue that these approaches constitute a new form of molecular description, analogous to clinical or pathological description, that alone does not hold the key to solving these complex diseases” (Click here to read more about this).
  • A review of studies demonstrating that dietary components/foods may be related to risk for Parkinson’s, which then proposes a model of microbiota-gut-brain-axis regulation of neuroinflammation in PD ( to read more about this).

  • Bradykinesia is one of the cardinal motor symptoms of Parkinson’s disease, but its mechanisms are not fully understood. This review explores recent findings on bradykinesia pathophysiology, including the role of network dysfunction ( to read more about this).
  • I did not realise that so much research has been conducted on long noncoding RNAs in the context of Parkinson’s – a nice review about part of the “junk DNA” ( to read more about this).
  • A mini-review based on the discussions of the 3rd NO-Age Symposium in Oct 2019 about the mechanisms & translation potential of NAD+, including the nicotinamide riboside clinical trial in Parkinson’s being conducted in Norway (Click here to read more about this).
  • Synucleinopathies: Where we are and where we need to go” – an interesting summary of the topics discussed at the Synuclein Meeting in Porto ( to read more about this).
  • Researchers discuss the genetic & epigenetic factors that might influence the number of substania nigral dopamine neurons that each individual is born with & how these could potentially be linked to Parkinson’s risk ( to read more about this).
  • Researchers provided a useful review of how dysregulation in mitochondrial crosstalk with other organelles may contribute to Parkinson’s pathogenesis ( to read more about this).
  • Researchers “advocate for a more rigorous & critical approach for inferring causality to avoid false concepts & prevent unrealistic expectations that may undermine the credibility of microbiome science & delay its translation” ( to read more about this).

  • Researchers provide a comprehensive review of vesicular dysfunction & some of the related genetics associated with the pathogenesis of Parkinson’s ( to read more about this).
  • For the history buffs: Pierre D. & the first photographs of Parkinson’s ( to read more about this).
  • A review of the emerging treatments for genetic forms of Parkinson’s – shifting away from a “one-size-fits all” approach towards more precision medicine (focus on LRRK2- & GBA-associated PD – to read more about this).
  • Researchers examine the relationship between the cannabinoid system & microglial activation, & how this association could be manipulated for therapeutic benefit in Parkinson’s ( to read more about this).
  • Researchers provide a review exploring immunotherapy for Parkinson’s. “Interventions that immunologically restore the brain’s homeostatic environment can lead to neuroprotective outcomes” ( to read more about this).
  • “The best available evidence recommends increasing physical activity levels in Parkinson’s. Exercise & physiotherapy programs seem the most efficacious strategies to achieve this goal” Useful review of research on exercise in PD, including defining concepts ( to read more about this).

  • Review of the characteristics of LRRK2-associated Parkinson’s that are most relevant to the development of LRRK2-targeted therapies, & the design/implementation challenges of clinical trials evaluating these new potential therapies ( to read more about this).
  • Interesting view point attempting to connect the possible role of protein aggregates in mitochondrial energy production for degenerative conditions like Parkinson’s (Click here to read more about this).
  • A useful review covering early studies to recent advances in our knowledge of the functional role of the Parkinson’s-associated PINK1-Parkin system ( to read more about this).
  • A thoughtful review of Parkinson’s-associated genetics. They cover a lot of bases here, including a great setction on future directions ( to read more about this).
  • An interesting proposal for changing the world of scientific publishing. “Social & technological innovation occurs at a snail’s pace because progress has been rendered a side-effect of research, rather than the goal”. They also discuss the need to “produce reference data & develop genetic tools specifically tailored to underserved populations” in the Parkinson’s community (Click here to read more about this).
  • Could heat therapy be an effective treatment for Alzheimer’s & Parkinson’s? Researchers provide a review of heat shock proteins & suggest that “emerging evidence is compelling & warrants further investigation”. Time for a sauna! ( to read more about this).

 

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

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

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EDITOR’S NOTE: The information provided by the SoPD website is for information and educational purposes only. Under no circumstances should it ever be considered medical or actionable advice. It is provided by research scientists, not medical practitioners. Any actions taken – based on what has been read on the website – are the sole responsibility of the reader. Any actions being contemplated by readers should firstly be discussed with a qualified healthcare professional who is aware of your medical history. While some of the information discussed in this post may cause concern, please speak with your medical physician before attempting any change in an existing treatment regime.

In addition, many of the companies mentioned in this post are publicly traded companies. That said, the material presented on this page should under no circumstances be considered financial advice. Any actions taken by the reader based on reading this material is the sole responsibility of the reader. None of the companies have requested that this material be produced, nor has the author had any contact with any of the companies or associated parties. This post has been produced for educational purposes only.


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