Monthly Research Review – April 2019

~ Simon

 

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 April 2019.

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

  • Basic biology
  • Disease mechanism
  • Clinical research
  • New clinical trials
  • Clinical trial news
  • Other news
  • Review articles/videos

 

So, what happened during April 2019?

In world news:

10th April – Scientists from the Event Horizon Telescope project announced the first ever image of a black hole. Located in the core of the Messier 87 galaxy (53 million light years from Earth), this supermassive black hole has a mass 6.5-billion times that of the Sun! The black hole’s boundary – the event horizon – is around 2.5 times smaller than the shadow it casts and measures just under 40 billion km across (about the size of Neptune’s orbit!!!).

 

10th April – Fossil fragments found in the Callao Cave in the Philippines revealled the existence of a new species of human, Homo luzonensis. The species is named after the island – Luzon – where it was discovered.

 

15th April – During Holy Week, a devastating fire engulfed the roof and main spire of Notre-Dame Cathedral in Paris.

 

24th April – I am a big fan of Martin. Several years ago his video of the Marble machine took the internet by storm and since then I have been following his regular vlog updates on the construction of the new and improved Marble machine X. This week he took the  new machine for its first test run – still has parts missing, but this is mesmerising to watch. If you don’t follow him you should!

 

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

In April 2019, there were 730 research articles added to the Pubmed website with the tag word “Parkinson’s” attached (3134 for all of 2019 so far). In addition, there was a wave to news reports regarding various other bits of Parkinson’s research activity (clinical trials, etc).

The top 9 pieces of Parkinson’s news

1. Felodipine and autophagy

University of Cambridge researchers reported that the L-type calcium channel blocker & anti-hypertensive drug, Felodipine, boosts waste disposal (or autophagy) in mouse brains. It clears mutant Parkinson’s α-synuclein in mouse brains at concentrations similar to those used in humans. The findings raise the possibility that this clinically available drug could be re-purposed for Parkinson’s ( to read more about this and click here to read the press release).

2. What we need to do is block CD22?

Microglial cells play an important role in maintaining homeostasis in the brain, by cleaning up waste (via a process called phagocytosis). As we age, this ability to maintain homeostasis becomes impaired. Genetic mutation screening experiments of age-related modifiers of microglial phagocytosis have identified CD22 (a canonical B cell receptor) as a negative regulator of phagocytosis. Inhibition of CD22 promoted the clearance of Parkinson’s-associated α-synuclein fibrils in mice. Inhibition of CD22 also promoted the clearance of Alzheimer’s-associated amyloid-β oligomers in mice. Long-term delivery of a CD22 antibody appears to reprogram microglia towards a homeostatic transcriptional state & improves cognitive function in aged mice ( to read more about this and click here to read a SoPD post on this topic).

3. Quantum imaging

Researchers presented the discovery of a novel quantum method of detecting & quantifying low levels of dopamine, which could potentially form the basis of better future detection & monitoring of Parkinson’s ( to read more about this and click here to read the press release).

4. Need to rethink our PARKIN

Mutations in PARKIN (PARK2) are among the most common genetic risk factors associated with early onset Parkinson’s. Researchers have developed a framework for classification of 51 PARKIN variants based on clinical & functional data. Interestingly, only a minority of PARKIN variants, even among those previously associated with Parkinson’s, were found to actually disrupt PARKIN function, and “a few of these naturally occurring PARKIN variants actually enhanced mitophagy” ( to read more about this).

5. GDNF gene therapy trial results

Glial cell-line derived neurotrophic factor (or GDNF) has been a topic of heated discussion in the Parkinson’s community for a long time. Most recently due to the announcement of the results of the Phase II Bristol GDNF clinical trial results, which did not meet the primary end points of the study (Click here to read more about that). At the annual American Association of Neurological Surgeons conference that was held in San Diego this month, the results of another GDNF clinical trial in Parkinson’s were presented. The results suggested that the treatment was safe and well tolerated, and the coordinators are now setting up a larger Phase II clinical trial (Click here to read the meeting abstract and click here to read a SoPD post on the results).

 

6. Gene therapy for dyskinesias

Michigan State University researchers demonstrated that that genetic silencing of striatal CaV1.3 calcium channels could have the potential to transform treatment of individuals with Parkinson’s associated Levodopa induced dyskinesias ( to read more about this).

8. Fox Insight Data Exploration Network

The Michael J Fox Foundation & the genetic company 23andMe have launched the “Fox Insight Data Exploration Network” (Fox DEN) which contains patient-reported outcomes & de-identified genetic data from the largest cohort in Parkinson’s research & useful data exploration tools ( to read more about this).

9. Obituary

The SoPD was sad to hear of the passing of Nobel laureate Prof Paul Greengard this month. Most readers will have little idea of his contributions to the field of neuroscience (let alone Parkinson’s). They were considerable ( to read more about his life).

 

Basic biology news

  • Lymphocyte activation gene-3 (LAG-3) is a potential therapeutic target for Parkinson’s. New study suggests LAG-3 on naive CD4+ T cells negatively regulates mitochondrial biogenesis & metabolism as a means of controlling homeostatic expansion & quiescence. Previous research suggests global knockout or antibody blockade of LAG-3 in non-obese diabetic mice accelerated type 1 diabetes. Metabolic enhancement of diabetogenic CD4+ T cells may confer greater activation & disease-inducing potential ( to read more about this).
  • A role for the circadian clock in a neurodegenerative disease? Reducing Heat Shock Protein 70/90 Organizing Protein (or Hop) in Huntington’s disease fly model reduces mHtt aggregation & toxicity ( to read more about this).
  • Several genes associated with Parkinson’s are involved in mitophagy (the removal of old/sick mitochondria). Now researchers have developed a powerful new tool that allows reversible induction of mitophagy using optogenetic stimulation ( to read more about this).

  • Researchers use immunoprecipitation + targeted proteomics (liquid chromatography & tandem mass spectrometry) to analyse alpha synuclein protein from the brain. They identified ~20 modified α-synuclein variants. None were Lewy body-specific ( to read more about this).
  • Researchers show that 3D differentiation of midbrain floor plate neural progenitor cells leads to organoids which display key features of both the healthy & Parkinson’s-associated LRRK2-G2019S midbrain ( to read more about this).
  • New study connects Parkinson’s-associated LRRK2 with PINK1- & PRKN-mediated mitophagy via its substrate RAB10, & indicate that the pathogenic effects of mutations in LRRK2, PINK1 & PRKN may converge on a common pathway (Click here to read more about this).
  • New study reports that non-aggregated α-synuclein promotes vesicle merger, but even minute amounts of soluble aggregated species abolish SNARE-dependent bilayer merger completely – potentially impairing neurotransmission. Implications for Parkinson’s? ( to read more about this).
  • New data suggests Parkinson’s-associated DJ-1 positively regulates anti-inflammatory functions of astrocytes; DJ-1 dysfunction contributes to the excessive inflammatory response in development of PD; PTGDS & PGD2 mediate anti-inflammatory effects of DJ-1 ( to read more about this).
  • Researchers report an integrated transcriptomics & proteomics analysis of mutations in Parkinson’s-associated LRRK2, which found dysregulation of 25 RABs & reveals alterations in endocytic pathways ( to read more about this).

  • Researchers present an iterative screening method that enables the isolation of microbial strains for increased L-DOPA production. Highlights genetic variants that increase L-DOPA levels – implications for Parkinson’s? ( to read more about this).
  • Scientists present ASYN-CONA: a novel bead-based assay for detecting early stage Parkinson’s-associated α-synuclein aggregation. They also provide evidence of Baicalein, curcumin & rifampicin inhibition of the α-synuclein aggregation ( to read more about this).
  • Transcriptomics-based screening identified pharmacological inhibition of Hsp90 as a means of “Deferring aging” ( to read more about this).
  • Researchers report that NIPSNAP1/2 are required for PARKIN-dependent mitophagy. NIPSNAP1-deficient zebrafish present Parkinson’s-like features & loss of dopamine neurons ( to read more about this).
  • Israeli researchers present novel Mannitol-based small molecules for inhibiting α-Synuclein protein aggregation. An attractive scaffold for the development of therapeutic agents for Parkinson’s? ( to read more about this).
  • Researchers report a high-throughput ultrasonication-based assay of rapid amplification of Parkinson’s-associated α-synuclein aggregates in cerebrospinal fluid (CSF). Seeding activity of CSF from people with PD was higher than controls ( to read more about this).
  • Gene expression profile in patients with Gaucher disease indicates activation of inflammatory processes – could similar processes be in effect in GBA-associated Parkinson’s? ( to read more about this).

  • “Irrespective of cognitive instrument or cohort assessed, TMEM106B acts as a genetic modifier for cognitive trajectory in Parkinson’s. Our results implicate lysosomal dysfunction in the pathogenesis of cognitive decline in two different proteinopathies” ( to read more about this).
  • Researchers have an interesting manuscript on BioRxiv that has identified multiple kinase inhibitors that significantly increased or decreased NURR1 activity – implications for Parkinson’s? ( to read more about this).
  • Researchers have a manuscript on BioRxiv suggested that enriched social environment can have a positive effect on the induction of Parkinson’s mediated inflammation in the intestine by changing anti-inflammatory gut bacteria (in mice – to read more about this).
  • Icariin – a flavonoid found in Horny Goat Weed – has been reported to reduce neuroinflammation & exerts dopamine neuroprotection via an Nrf2-dependent manner. Failed to work in Nrf2-mutant mouse model of Parkinson’s & also failed in neuron-alone cultures ( to read more about this).
  • Researchers report that binding of Parkinson’s-associated α-synuclein oligomers to the gap junction protein connexin-32 (Cx32) facilitates protein uptake & transfer in both neurons & oligodendrocytes. Therapeutic target? ( to read more about this).
  • Researchers add to growing evidence that Parkinson’s genetic variants may not lie entirely in those cell types that display the characteristic neuropathology, but instead in global cellular processes, with effects in a range of cellular types ( to read more about this).
  • Reseachers present quantitative characterisation of Parkinson’s-associated α-synuclein aggregation in living yeast cells. Inclusion formation is strictly concentration, but not time, dependent (threshold of A53T mutant is 56% of WT – to read more about this).

  • MicroRNA are tiny regulators of activity in our cells. Now Chinese researchers report that MicroRNA-124 may inhibit neuroinflammation during the development of Parkinson’s by targeting p62, p38, & promoting – a potential target for therapeutic intervention ( to read more about this).
  • Researchers have a manuscript on bioRxiv suggesting neuronal aging potentiates Alzheimer’s-associated beta-amyloid generation (via up-regulated by a specific age-dependent increase in amyloid precursor protein endocytosis – to read more about this).
  • New study finds that L-DOPA-quinone (a metabolite of L-DOPA) may mediate recovery of GIRK channel firing in dopamine neurons. This mechanism could counteract firing inhibition in dopamine neurons caused by GIRK opening ( to read more about this).
  • Interesting bioRxiv manuscript from Swedish researchers suggests that herpes simplex virus 1 can catalyse aggregation of the amyloid-beta (Aβ42) peptide which is a component of amyloid plaques in Alzheimer’s – implications for Parkinson’s? ( to read more about this).
  • Gene co-expression analysis of the human substantia nigra identifies BMP2 as a neurotrophic factor which can also promote neurite growth in cells overexpressing wild-type or Parkinson’s-associated A53T α-synuclein ( to read more about this).
  • Knowledge about neuron-intrinsic responses to inflammation in Multiple Sclerosis is limited. Researchers now report neuroinflammation leads to induction & toxic accumulation of the synaptic protein ‘bassoon’ (Bsn) in both mice & patients ( to read more about this).
  • This is interesting – a proof-of-concept study demonstrating a non-invasive AAV-CRISPR system for correcting transcriptional misregulation in broad brain areas. Could a virus injected in the arm be used to correct genes in the brain? Implications for Parkinson’s? ( to read more about this).

  • Researchers present focal stimulation of the sheep motor cortex with a chronically implanted electrode array mounted on a nitinol endovascular stent. Localised stimulation of brain tissue from within a blood vessel! Implications for Parkinson’s? ( to read more about this).
  • Researchers present a cell-penetrating peptide which blocks Toll-like receptor-mediated downstream signaling & ameliorates autoimmune & inflammatory diseases in mice. The authors propose it could be tested on Parkinson’s & Alzheimer’s ( to read more about this).
  • Researchers demonstrate that astrocytes bounce back from oxidative stress & do not forfeit their neuroprotective properties in models of Parkinson’s ( to read more about this).
  • New BioRxiv manuscript suggests that Parkinson’s-associated α-synuclein fibrils formed in the presence of β-synuclein are less cytotoxic, exhibit reduced cell seeding capacity & are more resistant to fibril shedding compared to α-Syn fibrils alone ( to read more about this).
  • A Michael J Fox Foundation supported research suggests that Parkinson’s-linked genetic variations alter basal & evoked neurotransmitter activity in the rodent striatum. Curiously, PINK1 knock outs have more differences compared to PARKIN, DJ-1 & LRRK2 KOs ( to read more about this).
  • Researchers report that the mitochondrial metabolic function of Parkinson’s-associated DJ-1 is modulated by 14-3-3β (in a hypoxia-dependent manner – to read more about this).
  • Fic-mediated adenylylation/AMPylation is a possible mechanism by which cells cope with alpha synuclein toxicity asscociated with Parkinson’s ( to read more about this).
  • Viruses in Parkinson’s about to go viral? Researchers report that viral mimetic priming enhances cell loss & inflammation in models of PD. Could viral infections be a factor in accelerating neurodegeneration? ( to read more about this).

 

Disease mechanism

  • Researchers have published an interesting paper describing how the absence of one Engrailed1 allele can enhance Parkinson’s-associated alpha synuclein pathology. A useful new double-hit model? ( to read more about this).
  • Researchers have conducted large-scale proteomic analysis of human brain & identified 579 proteins associated with cognitive trajectory in advanced age. Evidence for increased neuronal mitochondrial activity in cognitive stability regardless of pathology ( to read more about this).
  • The Parkinson’s-associated PARK10 gene USP24 is a negative regulator of autophagy. USP24 regulates autophagy by affecting ubiquitination & stability of the ULK1 protein. Elevated levels of USP24 in substantia nigra of a subpop. of people with idiopathic PD ( to read more about this).
  • Aptinyx Inc presented data in a Parkinson’s model in non-human primates demonstrating the reversal of cognitive deficits with novel NMDA receptor modulator, NYX-458 at the ADPD meeting ( to read more about this).

  • Further evidence suggesting that the Parkinson’s-associated G2019s LRRK2 genetic variant promotes mitochondrial fission & increases TNFα-mediated neuroinflammation ( to read more about this).
  • Scientists report that Mcl-1, a pro-cell survival protein, is increased in the mice with Parkinson’s-associated PARK2 genetic mutation, suggesting a compensatory mechanism during development. Reducing Mcl-1 results in PD-like phenotype ( to read more about this).
  • Researchers report that Parkinson’s-associated LRRK2-G2019S variant in neuroepithelial stem cells induces alterations in mitochondrial morphology, gene expression, & mitophagy. Increased number of mitochondria, but more fragmented ( to read more about this).
  • Small molecule kaempferol – a natural flavonol – has been found to protect mouse model of Parkinson’s by inhibiting NLRP3 inflammasome activation. It reduced cleaved CASP1 expression & disrupted NLRP3-PYCARD-CASP1 complex assembly ( to read more about this).
  • New manuscript on BioRxiv, researchers suggests that NLRP3 plays an inflammasome-independent role in constraining neutrophil & anti-helminth immunity in the lung. Implications for NLRP3 inhibitors for Parkinson’s? ( to read more about this).
  • Researchers report an age-dependent accumulation of oligomeric α-synuclein from impaired degradation activity in LRRK2-R1441G mouse model of Parkinson’s. Interesting: a selective enhancer of the chaperone-mediated autophagy (AR7) reduced the accumulation ( to read more about this).
  • Administration of phospholipase A2 purified from bee venom suppresses dopamine neuron cell death in a mouse model of Parkinson’s ( to read more about this).

  • Researchers from Gloriana Therapeutics & Cytosolv have published data suggesting widespread striatal delivery of GDNF from encapsulated cells prevents the anatomical & functional consequences of excitotoxicity. Potential for Parkinson’s? ( to read more about this).
  • Researchers report neurodegeneration & contralateral α-synuclein induction after intracerebral α-synuclein injections in the anterior olfactory nucleus of a Parkinson’s A53T mouse model ( to read more about this).
  • 3 classical neurotoxins used in models of Parkinson’s kill cells use different pathways: 1. Caspase-dependent cell death for 6OHDA; 2. MPP+ stimulated caspase-independent cell death; and 3. Rotenone activated both pathways So does PD involve necrosis, apoptosis or necroptosis? ( to read more about this).
  • Researchers report differences in astrocytes (supportive cells in the brain) may underlie selective subregional differences in vulnerability to Parkinson’s (VTA astrocytes protected both VTA & SN dopamine neurons from MPP+). They also found that GDF15 – a member of the TGFβ superfamily – is expressed 230‐fold higher in VTA astrocytes than SN astrocytes. GDF15 treatment is neuroprotective, whereas its knockdown diminished this effect ( to read more about this).

 

Clinical research

  • New study finds that cerebral glucose metabolism brain imaging in idiopathic REM sleep behavior disorder (iRBD) is different from Alzheimer’s & Parkinson’s. Brain [18F]FDG uptake in iRBD differs from PD, thus not allowing the prediction of phenoconversion ( to read more about this).
  • Researchers find that plasma miR-105-5p expression level may be able to differentiate idiopathic Parkinson’s from parkinsonian syndrome, essential tremor and other neurodegenerative conditions ( to read more about this).
  • Researchers report a higher probability of prodromal Parkinson’s is related to lower cognitive performance (Click here to read more about this).

  • Using the database of the Korean National Health Insurance Service from 2002 to 2015, 76,043 subjects (≥60 years old) free of Parkinson’s at baseline finds Statin “ever use” was significantly associated with a high risk of PD incidence ( to read more about this).
  • The results of the OBSERVE-PD study – a cross-sectional, international, observational study of 2615 people with Parkinson’s at 128 movement disorder centers in 18 countries – have been published. Improving the identification of advanced PD ( to read more about this).
  • Researchers have published a report describing the generation & validation of a dataset comprising multi-year whole-blood transcriptome data for the study of onset & progression of Parkinson’s ( to read more about this).
  • A BioRxiv manuscript describes analysis of cerebrospinal fluid from 76 people with or without infectious meningitis. The results find proteins associated with Parkinson’s (LRRK2 & alpha-synuclein) significantly elevated. A link between neuroinflammation & infection? ( to read more about this).
  • Using directional deep brain stimulation leads to study subthalamic nucleus anatomy during stimulation. Incidence of adverse effects low for posteromedial stimulation & placing the directional part of the lead above the STN may help control dyskinesias ( to read more about this).

  • Four Lewy pathology staging systems were applied to postmortem brains from 141 cases with Lewy bodies (Parkinson’s). Most cases adhered to the ‘Braak progression pattern’, but ‘failure to fit’ was highly dependent on staging system applied ( to read more about this).
  • Swedish researchers provide the first clinicogenetic description of Parkinson’s related to the GBA-S107L mutation. Two half‐brothers, both heterozygous carriers of S107L, exhibited an early onset PD ( to read more about this).
  • Researchers investigate the gender differences in how differently male & female Parkinson’s patients & caregivers assess the severity & burden of the condition ( to read more about this).
  • Report that the genetic heritability of dementia with Lewy bodies is nearly 60%! That is 2x previous estimates. Condition also has a positive correlation with education phenotypes, which is contrary to Alzheimer’s ( to read more about this).
  • Researchers used data from 28,568 cases of Parkinson’s to perform a genome‐wide association study based on age of PD onset. Some established PD risk loci show no significant effect ( to read more about this).
  • Researchers report that mapping of areas of apparent susceptibility on brain imaging data could allow for differential diagnosis of atypical Parkinson’s ( to read more about this).
  • Interesting report highlighting the development & initial testing of an algorithm to automatically detect medication ON & OFF states in Parkinson’s using wearable sensors. 91% accuracy, 94% sensitivity, 85% specificity ( to read more about this and click here for the press release).

  • A study involving 21 drug-naive people with Parkinson’s, 27 people with treated PD, & 10 healthy subjects as controls finds that circulating trace amines may constitute putative markers for early stage detection & progression of PD ( to read more about this).
  • German researchers find no association between Parkinson’s & autoantibodies against NMDA-type glutamate receptors (Click here to read more about this).
  • An interesting study of the barriers & facilitators of communication about OFF periods in Parkinson’s, based on qualitative analysis of patient, carepartner, & physician Interviews ( to read more about this).
  • The genetic architecture of Parkinson’s in Spain: 13 Spanish Research Centers, 92 collaborators and DNA from 7849 individuals – characterizing population-specific risk, differential haplotype structures, and providing etiologic insight (Click here to read more about this).
  • Analysis of blood serum samples from 370 people (both drug naïve Parkinson’s & control participants) from the Norwegian ParkWest study points towards microRNA signatures as classifiers of PD ( to read more about this).
  • NEDD8 ultimate buster 1 (NUB1) is an adaptor protein, may be able to differentiate Parkinson’s & dementia with Lewy bodies from Multiple Systems Atrophy (MSA). NUB1 is present in Lewy bodies in PD, but not glial cytoplasmic inclusions in MSA ( to read more about this).
  • A BioRxiv manuscript suggests a high dose, short-term tango intervention for people with Parkinson’s improved motor & non-motor aspects of PD, such as activities of daily living & sleep – with high levels of adherence (97.5% – to read more about this).

  • Researchers present a pilot study of the consistency of simultaneous sleep actigraphy measurements across all 4 limbs in people with Parkinson’s. No variation between dominant & non-dominant arms. Some discrepancy between upper & lower limbs ( to read more about this).
  • New study of burden of neurodegenerative conditions in the Eastern Mediterranean region from 1990‐2016 finds a 42.3% increase in age‐standardised prevalence rate of Parkinson’s over that period of time (compared to 0.01% for Alzheimer’s – to read more about this).
  • Interesting insights into Parkinson’s in KwaZulu-Natal (South Africa). Dyskinesias more frequent in Indian & caucasian patients ( to read more about this).
  • A 11.5 year follow‐up study of 503,497 participants in the China Kadoorie Biobank study, identified 603 incident diagnoses of Parkinson’s. When cardiovascular issues were assessed only prior stroke & adiposity were associated with higher risks of PD ( to read more about this).
  • Still on cardiovascular matters: A second paper out today suggests no significant differences in carotid artery arteriosclerosis plaque & intima-media thickness (IMT) between 68 people with Parkinson’s & 81 controls, but the PD progress was correlated with IMT ( to read more about this).
  • Researchers provide further evidence of mitochondrial electron transport chain dysfunction in multiple system atrophy (MSA) & Parkinson’s. Results suggest an influence on selective regional vulnerability to MSA ( to read more about this).

  • South Korean researchers suggest chronic renal dysfunction & dipstick‐positive proteinuria may be independent risk factors for the development of Parkinson’s in older adults ( to read more about this).
  • Lewy pathology in the CA2 region of the hippocampus is associated with cholinergic degeneration in Parkinson’s with cognitive decline ( to read more about this).
  • Parkinson’s-associated alpha synuclein mRNA levels are significantly increased in peripheral blood cells of people suffering from major depressive disorder compared to healthy control subjects ( to read more about this).
  • Researchers explore issues around home-based video recording for assessment. People with Parkinson’s are positive about being filmed at home, when a number of requirements are taken into account ( to read more about this).

 

New clinical trials

  • resTORbio Inc have announced the initiation of a Phase 1b/2a clinical trial of RTB101 (an orally administered, potent inhibitor of target of rapamycin complex 1 (TORC1)) alone or in combination with sirolimus, for Parkinson’s. The study will involve 45 people with mild PD (already on standard-of-care therapy) with & without GBA genetic variants, treated for 4-weeks in a multicenter, 2:1 randomised, double-blind, placebo-controlled trial evaluating the safety & tolerability of RTB101. This new trial is being conducted in New Zealand ( to read more about the trial, to read the press release, and click here to read a SoPD post on this topic).

  • New clinical study assessing the impact of a diagnosis of Parkinson’s on work has been registered. Investigators are seeking 1000 participants for this survey-based study, available via the EUPD network (Click here to read more about this).
  •  A clinical trial has been registered for testing pridopidine in people with Parkinson’s who suffer from levodopa-induced dyskinesias. A multicenter, randomized, double-blind, placebo-controlled study evaluating the treatment in 135 people (Click here to read more about this).
  • A new clinical trial of Bumetanide (a loop diuretic) in Parkinson’s has been initiated Nantes (France). The CUREPARK study is being conduced by B&A Therapeutics will involve 40 participants with PD being treated for 4 months (Click here to read more about this and click here to read a previous SoPD post on this topic).

  • New clinical trial investigating antihypertension medication Terazosin in people with Parkinson’s has been registered. This will be a small pilot study, assessing safety/tolerability; hope for a larger disease modification/efficacy study (Click here to read more about this).

 

Clinical trial news

  • Cerecor Inc has announced positive interim Phase I results for CERC-301, an NMDA receptor antagonist, being developed for the treatment of neurogenic orthostatic hypotension in Parkinson’s. All doses showed clinically meaningful increases over placebo ( to read more about this).
  • A randomised, controlled clinical trial of DL‑3‑n‑butylphthalide (isolated from Apium graveolens seeds) in 103 people with Parkinson’s found significantly greater improvements in the non‑tremor, PSQI & PDQ‑39 scores compared to the control group ( to read more about this).
  • Acorda Therapeutics have published new clinical data for their orally inhaled levodopa (CVT-301/Inbrija) for early morning OFF periods in Parkinson’s ( to read more about this).

  • The results of the Phase I safety/tolerability, pharmacokinetics & pharmacodynamics clinical trial of KM-819 (a FAS-associated factor 1 inhibitor) in healthy volunteers have been published. This drug is being developed for Parkinson’s ( to read more about this).
  • Multicentre, randomised controlled trial of PDSAFE – a physiotherapist-delivered fall prevention programme for people with Parkinson’s – did not reduce falling. Functional tasks improved & reduced fall rates were apparent among those with moderate PD ( to read more about this).
  • Among people with mild-to-moderate Parkinson’s, a mindfulness yoga program was found to be as effective as stretching & resistance training exercise in improving motor dysfunction & mobility, plus additional benefits of reducing anxiety & depression( to read more about this).
  • Cerevance reports key endpoints in Phase I clinical trial of novel Parkinson’s compound CVN424, which “acts on a novel, non-dopaminergic target protein present specifically in dopamine receptor D2-expressing medium spiny neurons in the indirect pathway” (Click here to read more about this).

  • A small, randomised, double-blinded, placebo-controlled clinical trial evaluating daily intranasal insulin treatment on cognitive & functional performance in Parkinson’s & Multiple Systems Atrophy (MSA) for 4 weeks suggests approach is safe. A larger study required ( to read more about this).
  • International Stem Cell Corporation has announced completion of enrollment & dosing in its Parkinson’s stem cell transplantation clinical trial. The 12th & final participant of the phase 1 clinical study has been successfully transplanted. Results are expected in 2020 ( to read more about this).

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  • A four week clinical trial of Clonazepam finds that it is safe & tolerable for short-term use in probable REM sleep behavior disorder in Parkinson’s. “No firm conclusion on efficacy of clonazepam was drawn due to limitations in the study design” ( to read more about this).
  • Aptinyx reports positive data from their Phase I clinical study of a novel NMDA receptor modulator, NYX-458, in healthy volunteers. This drug is being developed for the treatment of cognitive impairment associated with some cases of Parkinson’s ( to read more about this).

 

Other news

  • Bluerock therapeutics announced our new strategic collaboration and cross-licensing agreement with CRISPR-genome editing company Editas Medicine ( to read more about this).

  • IBM demonstrated how a finger nail sensor could be useful in diagnosing Parkinson’s (Click here to read more about this).
  • Time for a new definition of Parkinson’s? A call for “a classification according to the clinical picture instead of second-order symptoms” – “Neither oversimplifying the symptoms nor a rigid adherence to older models are of service anymore” (Click here to read more about this).
  • Interesting interview with the CEO of Herantis Pharma, Pekka Simula, about what the company is doing and has planned for Parkinson’s (Click here to read more about this)

 

Review articles/videos

  • An incredible resource: The “Hope list” of clinical trials for Parkinson’s ( to read more about this).
  • Researchers have provided a useful review of plant extracts & phytochemicals targeting α-synuclein aggregation in models of Parkinson’s (Baicalein, Curcumin,… all the usual suspects get a mention, plus a couple of new entrants – to reassd more about this).
  • A useful review of environmental factors implicated in the onset of sporadic Parkinson’s – from pesticides to heavy metals ( to read more about this).
  • A very useful update on what is considered best practice in deep brain stimulation for Parkinson’s – everything thing you need to know! ( to read more about this).
  • Interesting review of data on the endoplasmic reticulum chaperone GRP78/BIP/HSPA5 as a therapeutic target in models of Parkinson’s ( to read more about this).
  • A very thorough review of cerebral dopamine neurotrophic factor (CDNF) in the context of Parkinson’s from researchers involved with Herantis Pharma. It includes a very timely review of the various neurotrophic factors that have been clinically tested in Parkinson’s ( to read more about this).

  • Basically everything you need to know about our knowledge of glial phagocytic clearance (engulfing synapses, apoptotic cells, cell debris, & toxic proteins) in Parkinson’s ( to read more about this).
  • An interesting & very thorough review on the importance of immune signaling in neurodegenerative conditions (including Parkinson’s – to read more about this).
  • An interesting review of the difficulties of untangling the genetic & epigenetic mechanisms potentially underlying Parkinson’s. Also provides some interesting hypotheses on how local & global epigenetics in PD neurons could lead to future therapeutic targets ( to read more about this).
  • Interesting review looking at ceramides – a class of lipids – in the context of Parkinson’s: From recent evidence to new hypotheses ( to read more about this).
  • Researchers provide a useful review of in vitro models of synucleinopathies – sub‐dividing them into 3 main areas: (i) formation of aggregated structures, (ii) cellular dysfunctions, & (iii) sites of interaction & their downstream consequences ( to read more about this).
  • Researchers provide a thorough review of… well,… basically EVERYTHING to do with the selective vulnerability in synucleinopathies like Parkinson’s. From microbiota to heavy metals, a-syn species to pesticides – it’s all here ( to read more about this).
  • This is a really fascinating read about the GDNF for Parkinson’s discussion. Gives you a real taste of the conversations going on behind the scenes ( to read more about this).

  • A useful review/primer of GBA genetic variants & Gaucher disease in the context of Parkinson’s, leading from the genetics all the way through to clinical testing of new therapeutic approaches ( to read more about this).
  • Discussion on considerations regarding epigenetics of Parkinson’s using reprogrammed cells 1. Reprogramming is based on epigenetic modifications & resets the epigenetic pattern to 0 2. Epigenome of iPSC neurons differ substantially from native neurons ( to read more about this).
  • Researchers provide an interesting & very thorough review of dysregulation of lipid metabolism & its potential role in α-synuclein pathology observed in Parkinson’s ( to read more about this).
  • And finally, click here to watch an interesting video interview of Prof Anders Bjorklund – one of the founding fathers of the field of cell transplantation for Parkinson’s.

 

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

And there it is, just some of the highlights from April 2019 – 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 May!

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.

Published by Simon

I am the Director of Research at Cure Parkinson's. Before that I was working as a Parkinson's research scientist at the University of Cambridge where I conducted both clinical- and lab-based research on Parkinson's. I have worked in the Parkinson's research field for over 15 years - both academically and in biotech ventures. All of my views/opinions expressed here are solely my own, and may not reflect the views of my employer or associated parties.

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