Monthly Research Review – November 2018

~ 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 November 2018.

The post is divided into five parts based on the type of research (Basic biology, disease mechanism, clinical research, other news, and Review articles/videos). 

 

So, what happened during November 2018?

In world news:

4th November – Kiwi Mike Lloyd finished his 10th New York marathon! Diagnosed with Parkinson’s 6 years ago, his story is truly inspiring – “To me it’s a celebration of what I can do, & what we can do as people, rather than what we can’t do”

Oh, and did I mention he’s also blind?

Click here to read more about his most recent marathon and click here to see his website.

6th November – Mining company BHP suspended all rail operations in Western Australia after a train (consisting of 4 locomotives & 268 wagons) ladened with iron ore travelled over 92km (57miles) with no driver on board. It was finally deliberately derailed by the authorities. And that’s not the only crazy story out of Australia this month – check out Knickers the giant steer!

 

9th November – Supermarket Iceland had their Christmas advert banned in the UK because it was “deemed to breach political advertising rules” (Can anyone please explain to me why? I quite liked it):

 

11th November – New Zealand space company ‘Rocket Lab‘ announced the successful orbital launch and deployment of customer satellites – their first commercial project, named ‘It’s Business Time’ – at 16:50 NZDT (03:50 UTC – Click here for the press release). Little old NZ punching above its weight yet again. The launch can be seen from 20 minutes into this video:

 

22nd November – Engineers at the Massachusetts Institute of Technology announced that they have developed a model aircraft with no moving parts that is capable of flight. The age of ionic wind has begun.

 

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

In November 2018, there were 762 research articles added to the Pubmed website with the tag word “Parkinson’s” attached (7172 for all of 2018 so far – we should easily beat last years total of 7644). In addition, there was a wave to news reports regarding various other bits of Parkinson’s research activity (clinical trials, etc).

The top 8 pieces of Parkinson’s news

1. PARP-1 inhibitors rescue PD models

John Hopkins Medicine researchers find that Parkinson’s-associated alpha synuclein aggregates activate poly(adenosine 5′-diphosphate–ribose) (PAR) polymerase–1 (PARP-1), which leads to parthanatos cell death. PARP inhibitors rescue mouse models. The report suggests alpha synuclein is killing cells by activating PARP (via the parthanatos cell death pathway). PARP activation leads to increased levels of poly(adenosine 5′-diphosphate–ribose) (PAR) which goes on to accelerate alpha synuclein aggregation (in a feed-forward cycle). And the investigators also demonstrate that PAR levels are increased in the brains of people with Parkinson’s. In addition, they found that treating with clinically available PARP inhibitors significantly reduced levels of PAR in models of PD, which in turn resulted in less alpha synuclein aggregation. The only thought here is that PARP inhibitors are not great at crossing the blood brain barrier, so translating these results to people with Parkinson’s will be challenging ( to read more about this, click here to read a commentary, click here to read the press release, and click here to read a SoPD post on this topic).

2. A Scot­tish mouse, a Finnish pa­tient and Parkinson’s

Six years of work by researchers at Dunedee University provides fundamental information on how genetic mutations in the PARKIN gene affects Parkinson’s. Both mouse & human work combined in this stellar piece of research. Prof Miratul Muqit and colleagues at Dunedee University (and international collaborators) published a new mouse model of Parkinson’s, involving a very specific genetic mutation (PARKIN S65A). The mouse exhibits motor/movement issues, but no loss of dopamine neurons. Interestingly, the researchers also found two patients with early onset Parkinson’s, which appears to be progressing very slowly ( to read more about this and click here to read the press release)

3. An oral Exenatide?

Novo Nordisk researchers have published preclinical & clinical data on an oral tablet version of their GLP-1 agonist Semaglutide coformulated with the absorption enhancer sodium N-[8-(2-hydroxybenzoyl) aminocaprylate] (SNAC). Could there soon be an ‘exenatide’ pill for Parkinson’s? ( to read more about this).

4. The smell of Parkinson’s

The researchers behind the “super smeller” study have a manuscript available on biorxiv identifying volatile odorous compounds from patient sebum that associate with the “smell of Parkinson’s”. Sebum is a waxy fluid excreted by the skin, over-production (seborrhea) can be a symptom of PD. Samples collected from 64 subjects (21 controls & 43 PD) identifies a distinct volatiles-associated signature for PD, including altered levels of perillic aldehyde & eicosane. The manuscript still needs to go through the peer-review process before it is published, but if you would like to read the manuscript (there will be an SoPD post on this once it it published).

5. Smoking and Parkinson’s

A consortium of researchers who provide further evidence 4 a link betwn smoking & reduced risk of Parkinson’s – but they are not clear which chemical compound in smoking is responsible for the biological effect. The study found that existing smokers are up to 50 per cent less likely to develop. An inverse association between exposure to passive smoking at home and/or at work and risk of PD was also identified. And “the authors of the study warned the “disastrous” harms caused by tobacco continue to vastly outweigh any benefit related to the neurological disease” ( to read more about this and click here to read the press release).

 

6. Clusters of Parkinson’s

UK-wide study finds 4 novel clusters across two large independent early Parkinson’s cohorts – associated with L-dopa response & motor progression rates. Those clusters are:

  1. Fast symmetrical motor progression with poor olfaction & cognition
  2. Mild motor & non-motor disease with intermediate motor progression
  3. Severe motor disease, poor psych & sleep, intermediate motor progression
  4. Tremor-dominant, slow unilateral motor progression

Data has implications for understanding disease pathology AND patient stratification in future trials ( to read more about this).

7. Gene therapy induced changes in brain circuitry

Researchers present metabolic imaging data from the AAV-GAD gene therapy study in Parkinson’s which suggest that the clinical benefits are likely mediated by modulation of brain metabolism. AAV-GAD (NLX-P101) treatment produced “adaptive rewiring”, but deep brain stimulation which also suppresses subthalamic nuclei activity (using electrical pulses) did not. Researchers now seeking to re-explore this approach with another clinical trial in late 2019 ( to read more about this and click here for the press release).

8. A new player in town: HDAC4

Researchers at Oxford University have published an impressive report using high-resolution, single-cell transcriptomic analyses of patient-derived dopamine neurons (made from induced pluripotent stem cells or iPSCs) to identify histone deacetylase 4 (HDAC4) as a regulator of disease progression. Treating the iPSC-derived dopamine neurons with HDAC4-modulating compounds like Tasquinimod – an allosteric inhibitor of HDAC4 – upregulated genes early in the differentially expressed axis AND corrected Parkinson’s-related cellular phenotypes ( to read more about this).

Basic biology news

  • Parkinson’s-associated protein PARKIN targets nucleotide‐oligomerization domain receptor 2 (NOD2) to regulate astrocyte endoplasmic reticulum stress & inflammation ( to read more about this).
  • The human brain has a resident population of memory T cells (part of the immune system) which survey & provide protection against neurotropic virus reactivation. Remarkably consistent phenotype across conditions like Parkinson’s & Alzheimer’s ( to read more about this).
  • Copper acts as a neuronal signaling agent as well as an effector of Parkinson’s-associated alpha synuclein protein structure, aggregation, and localization. Now researchers have provides a detailed analysis (EPR spectroscopy) of aspects of this interaction ( to read more about this).
  • Japanese researchers have identified ubiquitin-specific protease 10 (USP10) as is a critical factor in the control of protein aggregation. USP10 induces alpha synuclein-positive aggresomes & is colocalized with α-synuclein in Lewy body in Parkinson’s ( to read more about this).
  • Epigallocatechin‐3‐gallate (EGCG) from green tea suppresses, disaggregates, & modulates γ‐Synuclein (a similar protein to Parkinson’s-associated alpha synuclein – to read more about this).

  • New study highlights the need for studies to further characterize mitochondrial protein import deficit in the context of Parkinson’s. TOM20 overexpression exacerbated neurodegeneration, while overexpression of TIM23 partially protects models of PD ( to read more about this).
  • Da-Bu-Yin-Wan – sounds like a character from Star Wars, but it is a traditional Chinese medicine that is used to treat Parkinson’s. New evidence suggests DBYW improves effects of DJ-1 on mitochondrial dysfunction (via Akt phosphorylation) in models of PD ( to read more about this).
  • Nuclear receptor-related 1 protein (Nurr1) is a therapeutic target for Parkinson’s. Now researchers have used NMR & HDX-MS to uncover a dynamic putative pocket. This finding should stimulate future studies into the druggability of Nurr1 ( to read more about this).
  • LRRK2 inhibitors are being developed for Parkinson’s. Now researchers report that HIF-1α-dependent transcriptional induction of LRRK2 exacerbates cell death in models of brain injury. Treatment with LRRK2 inhibitor G1023 substantially reduced damage ( to read more about this).
  • Researchers use a highly selective antibody & detect bacterial lipopolysaccharide in blood collected from individuals with Parkinson’s, Alzheimer’s, & diabetes (compared to controls). Close association with amyloid fibrils ( to read more about this).
  • HtrA2/Omi is a mitochondrial serine protease required for mitochondrial homeostasis in humans & mice. New manuscript on biorxiv suggests that HtrA2/Omi also removes Parkinson’s-associated oligomeric α-synuclein (without affecting monomers – to read more about this).
  • Lewy bodies in 3D!!! Dutch researchers have a manuscript on biorxiv which provides the detailed 3D structure of Parkinson’s-associated Lewy bodies & presents a novel hypothesis for the stages of their development ( to read more about this).

  • Brazil President Michel Temer inaugurated the opening construction phase of a massive particle accelerator called Sirius, that will be used for basic brain study research as well as degenerative diseases like Parkinson’s & Alzheimer’s ( to read more about this).
  • Interesting what the absence (& presence) of a little vesicular glutamate transporter 2 will do. Researchers find that reduced VgluT2 expression in dopamine neurons “may constitute a risk factor in the development of Parkinson’s” ( to read more about this).
  • Anle138b (an experimental compound from MODAG GmbH) modulates alpha‐synuclein oligomerization & prevents motor decline/ neurodegeneration in a mouse model of multiple system atrophy (MSA) – similar to Parkinson’s ( to read more about this).
  • Researchers report that the neural networks supporting aspects of timekeeping are split between 2 different parts of the brain, & rhythmic timing (associated with the basal ganglia) is affected in Parkinson’s ( to read more about this).
  • Interesting report highighting the importance of Mcl1 – a critical Bcl2 pro-survival factor – for dopamine neurons (a group of cells that are particularly affected in Parkinson’s – to read more about this).
  • Peptron Inc have published data involving their experimental Parkinson’s treatment PT302 (a long acting GLP-1 agonist – like Exenatide) which demonstrates that it can reduce neuronal cell loss in a mild brain trauma mouse model ( to read more about this).

  • Soluble epoxide hydrolase inhibitor, APAU, demonstrates protective effect on dopamine neurons in neurotoxin-induced models of Parkinson’s ( to read more about this).
  • Researchers report that ZSCAN21 regulates alpha synuclein protein levels. TRIM41 ubiquitinates ZSCAN21, & TRIM17 inhibits it… aaaaand they find that rare genetic variants in ZSCAN21, TRIM17 & TRIM41 genes occur in familial forms of Parkinson’s ( to read more about this).
  • New study suggests increased stress susceptibility in Parkinson’s-associated LRRK-G2019S context via inhibition of DAF-16 nuclear translocation (in a 14-3-3 associated-manner). Potential of 14-3-3 proteins as neuroprotective targets in PD. The study was performed in C.Elegans (flat worms) – DAF-16 is a homolog of mammalian FoxO ( to read more about this).
  • Tetracycline antibiotic Minocycline suppressed the age-dependent increase in Parkinson’s-associated α-synuclein aggregation in C.elegans. Also reduced α-syn aggregation when given at late age (day 8), when unfolded protein responses were no longer induced ( to read more about this).
  • Researchers have published data suggesting that pathogenic Parkinson’s-associated LRRK2, as well as increased levels of RAB7L1, cause RAB8A-dependent centrosomal deficits. A useful cellular readout for a broader spectrum of the condition? ( to read more about this).

 

Disease mechanism

  • Researchers find bile acids TUDCA & UDCA at significantly lower levels in prodromal Parkinson’s mouse model (compared to controls). The researchers ask if bile acids could be potential biomarkers for predicting PD ( to read more about this).
  • Whole-exome sequencing of Han Chinese with early onset Parkinson’s finds NUS1 (a type I single transmembrane domain receptor) harbours significantly more rare nonsynonymous variants than controls. Gene mutation in flies = dopamine cell loss & motor issues ( to read more about this).
  • Researchers report that nicotine protects against Parkinson’s by suppressing SIRT6. PD brains have raised levels of SIRT6. SIRT6 knockout mice are protected from MPTP. Data suggests that SIRT6 plays a pathogenic & pro-inflammatory role in PD ( to read more about this).
  • AMP kinase (AMPK) is a master regulator of cellular energy homeostasis. New research finds that AMPK activation is selectively disrupted in the ventral midbrain of mice deficient in Parkinson’s-associated PARKIN. Metformin treatment selectively restores it ( to read more about this).
  • Researchers report that Ghrelin & JMV-2894 (a novel growth hormone secretagogue) have no effect on transplanted cell survival (or function) in models of Parkinson’s ( to read more about this).
  • Pharmaceutical company Lundbeck has a manuscript on biorxiv reporting chronic LRRK2 inhibition using PFE-360 partially restores motor function in an alpha synuclein model of Parkinson’s, but effect is independent of the STN burst firing & neurodegeneration ( to read more about this).

  • New research suggests that different species of Parkinson’s-associated protein alpha synuclein in cerebrospinal fluid could be useful as part of a biomarker panel for dementia with Lewy bodies ( to read more about this).
  • By investigating the combination of environmental factors & genetic susceptibility, researchers found that GSTT1−/− midbrain dopamine neurons are hypersensitive to the pesticide propargite. Could decreased GSTT1 levels be a risk factor for Parkinson’s? ( to read more about this).
  • A new manuscript on biorxiv suggests that heightened corticosterone levels aggravates neurodegeneration & alpha-synuclein pathology – intriguingly in specific brain areas – in models of Parkinson’s ( to read more about this).
  • Researchers provide a dynamic picture of Parkinson’s-assocaited PARKIN activation, whereby PINK1 phosphorylation of PARKIN & E2~Ub recruitment co‐operate to drive PARKIN activity ( to read more about this).
  • Researchers find that ubiquitin-specific protease 10 (USP10) not only induces alpha synuclein-positive aggresome, but is also present in Lewy bodies (LB) in Parkinson’s brain. Data supports the idea that USP10 plays a role in LB formation ( to read more about this).

  • Scottish researchers have just published a new study demonstrating that reducing/removing alpha synuclein genetically – using CRISPR gene editing – results in a measure of resistance to Parkinson’s Lewy body pathology ( to read more about this).
  • Pα-syn* – a novel species of Parkinson’s-associated alpha synuclein protein – has been shown to trigger of a series of kinase mediated pathogenic events & involves tau phosphorylation & aggregation at the mitochondria ( to read more about this).

 

Clinical research

  • Australian researchers used Parkinson’s medication usage to estimate prevalence in 79 localities in Victoria (5.3 million people). They found prevalence not associated with rurality, but associated with pulse production. Pulses are plants of the fabaceae family ( to read more about this).
  • Analysis of cerebrospinal fluid – the liquid your brain sits in – from 80 controls & 80 people with early Parkinson’s highlights changes in 6 potential biomarkers (α-syn, DJ-1, Aβ42, S100β, p-Tau & t-Tau). Only Aβ42 could be validated in independent cohort ( to read more about this).
  • Excessive beta oscillatory activity in the subthalamic nucleus (STN) is linked to PD. Now researchers have found that differential contributions of subthalamic beta rhythms & 1/f broadband activity affect the motor symptoms in Parkinson’s ( to read more abou this).
  • A 3 year analysis of 1741 individuals with Parkinson’s suggests that there was no difference in disease progression as a result of vitamin D supplement use ( to read more about this).

  • A rare loss‐of‐function genetic variation in the PTRHD1 in an african family results in a autosomal‐recessive juvenile‐onset form of Parkinson’s with associated intellectual disability ( to read more about this).
  • Researchers provide a population-based cohort study of Ldopa-induced dyskinesias in Parkinson’s. 309 participants with PD, 279 (90.3%) received Ldopa. Dyskinesias in 84 of 279 patients (30.1%), Ldopa initiation to dyskinesia onset= 4 yrs ( to read more about this).
  • The Luxembourg Parkinson’s study: a large, longitudinally followed, & deeply phenotyped set of PD patients & controls ( to read more about this).
  • Researchers have published a study of life span pigmentation changes of the substantia nigra detected by neuromelanin‐sensitive MRI – a remarkable piece of work ( to read more about this).
  • Cerebrospinal fluid samples from 32 people with early-stage PD & 28 control suggest levels of ‘autophagy’ (the cellular waste disposal system)-related proteins represent potentially novel biomarkers of early-stage Parkinson’s ( to read more about this).
  • Interesting resesarch from cohort analysis in Egypt suggests that individuals with K-variant in the butyrylcholinesterase gene BCHE appear to have an increased risk for Parkinson’s when exposed to pesticides. SNP rs1126680 in BCHE reduced risk of PD ( to read more about this).

  • Interesting discussion regarding the use of several recruitment strategies for a randomised exercise clinical trial in Parkinson’s (the SPARX Study Group – to read more about this).
  • Researchers have analysed the Parkinson’s Progression Markers Initiative (PPMI) data to find risk factors for L-dopa induced dyskniesias in a cohort of recently diagnosed people with PD. 7 risk factors for LID development were identified ( to read more about this).
  • Researchers present results that are suggestive of a novel association between genetic variants in the opioid receptor gene OPRM1 and impulse control disorders & related behaviours in Parkinson’s (they also confirm association with DAT variants – to read more about this).
  • 3 year follow up study suggests that 18F-AV-133 vesicular monoamine transporter type 2 (VMAT2) brain imaging is a useful tool in improving diagnostic accuracy in clinically uncertain Parkinson’s syndromes (CUPS – to read more about this).
  • Researchers report that 24-hour levodopa-carbidopa intestinal gel can reduce troublesome dyskinesias in advanced Parkinson’s (in 9 out of 12 patients – to read more about this).
  • New study suggests that losing the function of LRRK1 & LRRK2 (via genetic mutations/variants) does not increase the risk of developing Parkinson’s. Results suggest that drugs inhibiting mutant LRRK2 protein remains a viable therapeutic strategies for PD ( to read more about this).

  • Baseline predictors of worse progression of motor symptoms in Parkinson’s include being male, orthostatic blood pressure drop, coronary artery disease, arterial hypertension, elevated serum uric acid, & CSF neurofilament light chain ( to read more about this).
  • Researchers have published a study investigating wearable sensors for Parkinson’s which suggests PD symptoms can be detected during a variety of activities & are best modelled by a dataset incorporating many individuals ( to read more about this).
  • Dutch researchers have published a mass spectrometry experiment of cerebrospinal fluid suggesting that Galectin-1 protein levels can be used to discriminate people with Parkinson’s from controls ( to read more about this).
  • VMAT2 is involved in the production of dopamine. Brain imaging of VMAT2 activity finds that it is reduction in the external globus pallidus regardless of Parkinson’s stage, while the internal GP had reduction only in more severe cases ( to read more about this).
  • Researchers provide evidence that atrophy of the vagal nerve in people with Parkinson’s can be detected using high-resolution ultrasound ( to read more about this).

  • Plasma neurofilament light (NFL) has been found to be significantly higher in the Parkinson’s with dementia compared with the PD without dementia. High plasma NFL correlated with poor cognition in Alzheimer’s & PD, but not with motor symptoms in PD ( to read more about this).
  • Freezing is a disabling symptom of Parkinson’s. Now Canadian researchers propose a new method (based on quiet stance baseline) that is more effective in identifying freezing in PD ( to read more about this).
  • New report supports the idea of distinct strains of the protein alpha synuclein may underlie Parkinson’s & multiple system atrophy (MSA). Soluble & insoluble fractions of MSA extracts had robust seeding activity, but only insoluble fractions seeded in PD ( to read more about this).
  • Serum levels of soluble Lymphocyte activation gene‐3 (LAG‐3) in people with Parkinson’s were significantly higher than those in essential tremor & age‐ and sex‐matched controls. New biomarker? Associated with non‐motor symptoms & excessive daytime sleep ( to read more about this).
  • Singapore scientists have found that Parkinson’s-linked CHCHD2 mutations cause an inability to interaction with CHCHD10, resulting in impaired mitochondria function. They also find that Elamipretide (MTP-131) can partially restore mitochondria function (Click here to read more about this).

 

Clinical trial news

  • Initial analysis of 18 month data from the Living Cell Technologies Limited Phase IIb clinical trial of NTCELL (a cell based therapy for Parkinson’s) suggests a statistically significant improvement (p = <0.05) in the UPDRS in one cohort of the 18 person study ( to read more about this).
  • ACADIA Pharmaceuticals have published preliminary data for their antipsychotic pimavanserin (aka Nuplazid), a selective serotonin 2A receptor inverse agonist, in people with Parkinson’s with cognitive impairment ( to read more about this).
  • International Stem Cell Corporation have announced 12-month results of the first cohort & six-month interim results of the second cohort of its currently-ongoing, open-label Phase 1 clinical study of stem cell transplantation in Parkinson’s ( to read more about this).
  • Gene therapy biotech Voyager therapeutics announces further long-term results from their Phase 1b clinical trial AND provide details of the new randomized, placebo-controlled Phase 2 study (24 sites; patient screening efforts are underway – to read more about this). BUT the US FDA has informed Voyager Therapeutics that they are currently considering the new Phase 2 trial as an early phase exploratory study. Meaning that they will probably require more clinical testing/data ( to read more about this).

  • An brief update from the Kyoto cell transplantation trial for Parkinson’s. This clinical study involves the injecting of neurons derived from induced pluripotent stem cells (iPS cells) into the brains of people with PD ( to read more about this and click here to read a previous SoPD post on this topic)
  • Global Kinetics Corp announce that their PKG® Smartwatch provides clinically meaningful improvement in Parkinson’s symptom assessment, management & medication optimisation (across 17 countries with 3,000,000+ hours of clinical data – to read more about this).
  • An interesting qualitative evaluation of the Global Kinetics Corp’s KinetiGraphTM Movement Recording System in a Parkinson’s clinic setting from researchers at the Parkinson’s Institute ( to read more about this).

  • New research involving mouse & human (from the Safety of Urate Elevation in Parkinson’s (SURE-PD) study) data does not support a hypertensive effect of urate elevation or an association between urate ( to read more about this).
  • Pfizer researchers report the first evidence of potential anti-Parkinson’s efficacy of the oral selective D1/D5 partial agonist PF-06412562, without the significant acute changes in cardiovascular parameters reported with previous D1 agonists ( to read more about this).
  • Smart socks! Sensoria is teaming up with the Michael J Fox Foundation & Neural Australia to launch the “Standing Tall-PD” study – a 100-participant clinical trial looking at what smart textiles in socks can do for Parkinson’s ( to read more about this).

Other news

  • Very interesting consensus white paper from the Michael J Fox Foundation: A proposed roadmap for Parkinson’s proof of concept clinical trials investigating compounds targeting alpha synuclein. It “provides a translational framework, from the selection of animal models & associated end-points to decision-driving biomarkers as well as considerations for the design of clinical proof-of-concept studies” for Parkinson’s therapies targeting alpha synuclein ( to read more about this).
  • Berg Health, who integrate artificial intelligence & patient biology, presented clinical target validation data for the treatment of Parkinson’s AND a novel mechanism of action (PIG3 as a novel therapeutic target –  to read more about this).

  • A fascinating feature looking at how social media & the digital age is changing clinical trials was published this month. Some of the take aways that resonated for me: “Recruitment and retention rates [for clinical trials] are the worst that they’ve been since the Tufts Center for the Study of Drug Development started tracking them 20 years ago”. And: “The advent of social media has made it much easier to ‘unblind’ a study” – Pat Furlong, founder of Parent Project MD. And this: “Many of the companies understand that we can’t do this now without patients being equal partners,” Deputy CEO Sohini Chowdhury – Michael J Fox Foundation (Click here to read the feature).
  • AC Immune has been awarded a 3rd follow-up research grant from Michael J Fox Foundation for a 1st-in-human clinical study of a Positron Emission Tomography (PET) tracer that targets the Parkinson’s-associated protein alpha synuclein. A new method of assessment? ( to read more about this).

  • “Hello April” – AI helping with Parkinson’s – UCB & Verint announce launch of UCB’s PD coach app equipped with a patented conversational, virtual health assistant named “April,”, powered by Verint’s Intelligent Virtual Assistant ( to read more about this).
  • UK-based MISSION Therapeutics & pharmceutical company AbbVie have joined forces to develop deubiquitinases inhibitors for the treatment of Parkinson’s & Alzheimer’s. The collaboration does not include any of Mission’s lead DUB programs (eg. USP30 & USP10 – to read more about this).

  • Inflazome secures funding to advance the clinical trials programme of their orally-available NLRP3 inflammasome inhibitor compounds in several chronic inflammatory conditions. Look forward to hearing news of a trial for Parkinson’s soon ( to read more about this).
  • Coeptis Pharma has entered an agreement to acquire Elto Pharma (a joint venture between Amarantus Bioscience & PsychoGenics). Elto Pharma is developing eltoprazine, which is in Phase IIb clinical development for Parkinson’s-associated levodopa-induced dyskinesias ( to read more about this).

 

Review articles/videos

  • Interesting review of the neuroprotective effects of baicalein in animal models of Parkinson’s ( to read more about this).
  • Parkinson’s UK held their Florence Pite Memorial Lecture evening highlighting interesting new technology to help solve issues with Parkinson’s. Unfortunately I couldn’t be there, but they have kindly made a video of the event available. Of particular interest is a fascinating presentation from Prof Jackie Hunter from Benevolent AI. An amazing overview of how artificial intelligence has been used to aid in drug discovery for ALS/motor neurone disease (target indentification ❤ months; preclinical candidate <12 months!). Now the same is being done for Parkinson’s (via a collaboration between Parkinson’s UK and the Cure Parkinson’s Trust):
  • Interesting review of the data on prodromal features of Parkinson’s from the team at the PredictPD study ( to read more about this).
  • Interesting review of the components & pathways behind the vesicular routes possibly involved in alpha synuclein trafficking in Parkinson’s ( to read this review).

  • Interesting discussion on best practices for translational disease modeling using human induced pluripotent stem cells (iPSC)-derived neurons – this source of cells in now being used in the Kyoto cell transplanation clinical trial for Parkinson’s ( to read more about this).
  • Interesting review of compounds characteristic of the Mediterranean Diet (such as resveratrol & oleuropein) & their ability to reduce microglia-mediated neuroinflammation in conditions like Parkinson’s ( to read more about this).

 

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

And there it is, just some of the highlights from November 2018 – another very busy month of Parkinson’s research. Hopefully there will be bits and pieces of interest for everyone in the list. Much of the material used here was collected from the Science of Parkinson’s Twitter feed (and there is a lot more posted there each day).

Any thoughts/feedback would be greatly appreciated (either in the comments below, or contact me directly).

And now: on to December! Christmas is almost here.

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.

4 thoughts on “Monthly Research Review – November 2018”

  2. In the Top 8 pieces of Parkinson’s news, item number 7 (Gene therapy induced changes in brain circuitry) looks very interesting. The research paper is behind a paywall, but there is now a good article on it at the AlzForum website. For me, one of the most-significant revelations is that the new clinical trial planned for 2019 is a Phase 3 trial.

    “The findings have sparked plans by a new company to take the therapy into a Phase 3 trial.”

    “Based on these new imaging data, a British gene therapy company has acquired the rights to the AAV2-GAD therapy, Eidelberg said. He declined to name it because the company has not yet made a public announcement.”

    https://www.alzforum.org/news/research-news/imaging-data-resurrects-abandoned-parkinsons-gene-therapy

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  3. Simon- I thoroughly enjoyed our brief experience with a round table at WPC in Kyoto. About 20 members of our local support group are regular readers of this site. My MDS has suggested I consider participating in the Biogen BBIIB094 study. Can you address AOS in an upcoming post? A.C. Woolnough

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    1. Hi AC,
      I hope all is well and that you’re enjoying a nice autumn in your neck of the woods. The BIIB094 study is an interesting endeavour – it is an antisense oligonucleotide approach targeting Leucine Rich Repeat Kinase 2 (LRRK2) mRNA (https://www.ionispharma.com/indications/parkinsons-disease/). It is also a topic that we have already discussed on the SoPD – though at the time of publishing that post it was not entirely clear what BIIB094 did (https://scienceofparkinsons.com/2019/06/14/antisense/). Let me know if anything doesn’t make sense.
      Kind regards,
      Simon

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