Monthly Research Review – May 2022

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At the end of each month the SoPD writes a post which provides an overview of some of the major pieces of Parkinson’s-related research that were made available during May 2022.

The post is divided into 10 parts based on the type of research:

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So, what happened during May 2022?

In world news:

May 6th – The 2022 monkeypox outbreak began when the first case was reported in London (United Kingdom).

 

May 12th – The Event Horizon Telescope collaboration revealed its first image of Sagittarius A*, a supermassive black hole at the centre of the Milky Way.

 

May 12th – Researchers announced that they were able to grow plants in soil samples from the moon collected by the Apollo astronauts in the 1970s (Click here to read more about this).

 

May 17th – Angel Alvarado (aged 19) set a new world record of four and a half minutes — breaking his own record by 20 seconds – for solving three Rubik’s Cubes at the same time while juggling them:

 

May 24th – I don’t care what anyone says, school shootings really upsets me – and this only happens in the USA (the length of the Wikipedia page on US school shooting statistics truly defies belief – it is utterly incomprehensible – but the fact that nothing is going to change in the wake of the latest tragic situation is the part that is really shameful).

 

May 25th – Engineers present a submillimeter-scale multimaterial remote-controlled walking robot. At only a half-millimeter wide, these tiny ‘crabs’ can bend, twist, crawl, walk, turn and even jump (Click here to read their report and click here to read the press summary).

 

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

In May 2022, there were 825 research articles added to the Pubmed website with the tag word “Parkinson’s” attached (5,345 for all of 2022 so far). In addition, there was a wave to news reports regarding various other bits of Parkinson’s research activity (clinical trials, etc).

The top 5 pieces of Parkinson’s news

1. MODAG’s Phase Ib results:

The results of a Phase 1b randomised, double-blind, placebo-controlled clinical trial evaluating the safety, tolerability & pharmacokinetics of MODAG’s alpha synuclein oligomer modulator anle138b (which is being developed for Parkinson’s) were published. The treatment was safe and well tolerated at doses that were efficacious in preclinical studies. Roll on Phase 2! (Click here to read more about this).

2. A positive Phase III result for Amyotrophic lateral sclerosis:

A Phase 3 randomized clinical trial that enrolled 130 participants with early-stage ALS & moderate progression rate reported that ultrahigh-dose methylcobalamin (vitamin B₁₂) significantly slowed progression (ALSFRS-R total score) over a 16-week study. The ALSFRS-R total score at week 16 of the randomized period was 1.97 points greater with methylcobalamin (50 mg) than placebo (−2.66 vs −4.63; 95% CI, 0.44-3.50; P = .01). There were no differences in adverse events between groups. What was the potential mechanism of action behind this effect? Methylcobalamin/VitB12 plays a role in removing homocysteine (the build up of which is believed to be toxic), and blood homocysteine levels are increased in ALS, so perhaps high dose VitB12 may be reducing it (Click here to read more about this).

3. Improved characterisation of dopamine neuron subpopulations:

Researchers collected postmortem midbrain tissue from 8 control donors & performed single cell sequencing, identifying 10 populations of dopamine neurons. Using macaque midbrains, they spatially localized each within the substantia nigra pars compacta. Next they performed similar analysis on samples of brains from Parkinson’s & Lewy body dementia postmortem cases. Transcriptional changes in cells that expressed AGTR1 point towards several canonical cell stress pathways (TP53 and NR2F2) as important to the process of PD-associated neuronal death (Click here to read more about this and click here to read the editorial).

4.  Are beta agonists a better bet?:

Previous research had indicated that beta2-adrenoreceptor agonists could reduce the amount of alpha synuclein protein in cells and epidemiological data suggested that use of this class of drugs reduced one’s risk of developing Parkinson’s (Click here to read a previous SoPD post on that research). Now a new research report has found that the beta2-adrenoreceptor agonist clenbuterol does produce a decrease in Parkinson’s-associated alpha-synuclein mRNA, but it is only transient. And when the researchers tested this drug in models of Parkinson’s, they saw no long-term reduction in alpha synuclein protein levels (Click here to read more about this).

 

5. Impressive data from the Verily Study Watch:

Researchers recruited 388 individuals with early-stage Parkinson’s and asked them to wear the Verily Study Watch. They tracked them over time – for a median of 390 days (Dropout rate=5.4%; Median wear-time=21.1 h/day). The investigators found that “Weekly measurements provide a real-life distribution of disease severity, as it fluctuates longitudinally” (Click here to read more about this and click here to read a press summary).

 

Articles of general interest

  • A call to action for including people with Parkinson’s in clinical study design and execution (Click here to read more about this).
  • Calling all ladies with PD to complete the first ever female-specific Parkinson’s survey on the Michael J Fox Foundation’s Fox Insights website (Click here to read more about this)

  • The 2022 update on the pipeline of Parkinson’s drug therapies in the clinical trial (Click here to read more about this).
  • Interesting write up on projects being undertaken at the ASU-Banner Neurodegenerative Disease Research Center at Arizona State University focused on cell transplantation for individuals with PD plus PARKIN genetic variants (Click here to read more about this).
  • Parkinson’s in Africa:
  •  Join the UK Parkinson’s Disease Clinical Studies Group – they are recruiting new PPI members. Full details about this exciting opportunity are on their website or contact our Coordinator, Emma Davies md4ecd@sheffield.ac.uk
  • Some Spring time reading on Parkinson’s research from Cure Parkinson’s (Click here to read more about this).

Basic biology news

  • New paper explores the kinetic parameters that control most effectively the generation of oligomers (Click here to read more about this)
  • Building on previous research, researchers screened a 45–54 peptide library against 5 of the known α-synuclein single-point mutants associated with early-onset Parkinson’s, highlighting 5 peptides that reduced aggregation (Click here to read more about this).
  • New paper presents a method for generating dopamine neurons from induced pluripotent stem cells; They express appropriate A9 (but not the A10) markers. Functionally, they exhibit autonomous pacemaking & rescued a rat model of Parkinson’s (Click here to read more about this).

  • New biorxiv manuscript reports that the cerebellum directly, rapidly, & effectively modulates basal ganglia dopamine levels & conveying movement initiation, vigor, & possibly reward information (Click here to read more about this). The “Nigro-striatal N-glycome”. A new biorxiv manuscript reports region-specific changes in tissue protein N-Glycosylation & associated molecular signatures in the Parkinson’s brain (Click here to read more about this).
  • Parkin deficiency impairs mitochondrial DNA dynamics and propagates inflammation – understanding the genetics and pathophysiology informs us (Click here to read more about this).
  • New biorxiv manuscript provides unbiased stereological estimates of dopaminergic and GABAergic neurons in the A10, A9, & A8 subregions in the young male macaque (Click here to read more about this).
  • Loss- & gain-of-function studies indicate that low expression of Parkinson’s-associated GBA1 promoted metastasis of liver cancer (in vitro & in vivo); Wnt/β-catenin signalling pathway involved; increased GBA1 may be a possible strategy for liver cancer (Click here to read more about this).
  • New research examines how the presence of a 9-residue fragment of the envelope protein of SARS-COV-2SK9 affects the conformational ensemble of Parkinson’s-associated α-synuclein monomers & the stability of two resolved fibril polymorphs (Click here to read more about this).

  • New research finds that proSAAS – a small secreted chaperone protein – provides neuroprotection & attenuates transsynaptic α-synuclein spread in rodent models of Parkinson’s (Click here to read more about this).
  • More single cell transcriptomics research highlights 5 genes (ANGPT2, APOD, HSP90AA1, HSPA1A, & PDE1C) that were up-regulated in Parkinson’s patients endothelial cells (compared to controls – click here to read more about this).
  • New paper examines detection of Parkinson’s-associated LRRK2 activity in cells & tissue (via Western blot with pS1292-LRRK2 or pT73-RAB10 antibodies); Overexpression is detectable, but endogenous LRRK2 activity not so much (Click here to read more about this).
  • New study reports that Excitatory Amino Acid Transporter 2 (EAAT2) trafficking is impaired by the Parkinson’s-associated LRRK2-G2019S variant; Could extracellular glutamate overload contribute in LRRK2-PD? (Click here to read more about this).
  • Accumulation of abnormal transactivation response DNA-binding protein of 43 kDa (TDP-43) independently induces dopaminergic neuronal loss in the substantia nigra without Lewy pathology, & results in typical Parkinson’s-like motor symptoms (Click here to read more about this).
  • New research presents the structural basis for feedforward control in the PINK1/Parkin pathway; Parkin has 2 binding sites for phosphorylated ubiquitin: 1. recruits Parkin to mitochondria, 2. switches on ligase activity (Click here to read more about this).

  • Pantothenate kinase 2 interacts with PINK1 to regulate mitochondrial quality control via acetyl-CoA metabolism; PANK2 mutant flies display similar mitochondrial abnormalities to Parkinson’s-associated PINK mutant flies; Dietary vitamin B5 rescues PINK flies (Click here to read more about this).
  • New biorxiv manuscript finds that Parkinson’s-associated mutations in DNAJC6 cause lipid defects & neurodegeneration that can be rescued by Synj1 (Click here to read more about this).
  • New research identifies distinct & shared impacts of alpha-synuclein variants on the epigenome, & associates alpha-synuclein with the epigenetic etiology of Parkinson’s (Click here to read more about this).
  • New paper reports the EEG phenotype of Parkinson’s-related GBA-mutation (D409V/WT) mice; Specific structural changes in the more widespread sleep neurocircuitry; Findings are in keeping with human data (Click here to read more about this).
  • “Irrespective of membrane location, the recruitment of LRRK2 to membranes results in local accumulation of phosphorylated RAB10, RAB12, & JIP4″ – researchers present on the complexities in the regulation of Parkinson’s-associated LRRK2 substrates (Click here to read more about this).

  • New research finds that Parkinson’s-associated PARK7/DJ-1 is a pacemaker regulating pyruvate dehydrogenase activity in CD4+ regulatory T cells; DJ-1 is highly expressed in human Tregs & depletion impairs Treg proliferation/activation in aged mice (Click here to read more about this).
  • New biorxiv manuscript identifies single mutations in the Endophilin-A flexible region that either increases Endophilin-A diffusion & promotes autophagosome formation in the absence of calcium (Click here to read more about this).
  • An experimental biology meeting presentation abstract proposes domestic crickets (Acheta domesticus) as an animal model to study Parkinson’s (Click here to read more about this).
  • Another experimental biology meeting presentation abstract reports that LRRK2 inhibition reduces neuronal damage & immune response after spinal cord trauma – potential for LRRK2 inhibitors beyond Parkinson’s? (Click here to read more about this).
  • Another experimental biology meeting presentation abstract reports a novel role for GCase activity in models of Parkinson’s: Reducing NLRP3 inflammasome activation (both in vitro & in vivo); Look forward to the paper (Click here to read more about this).

Disease mechanism

  • New research finds that a Cholecystokinin analogue & the GLP-1R agonist Liraglutide both restored the disruption of intestinal tight junction, decreased colonic inflammation, & inhibited gut dopaminergic neurons death & α-syn oligomers in Parkinson’s mouse models (Click here to read more about this).
  • Acidified drinking water attenuates motor deficits and brain pathology in a mouse model of Batten disease by significantly altering the gut microbiota composition; It also decreased the amount of lysosomal storage material, microglia activation, & astrocytosis (Click here to read more about this).
  • Could Nurr1 modulation by statins be responsible of the neuroprotective effects observed in preclinical models of Parkinson’s? New research indicates yes (Click here to read more about this).

  • New research explores parthanatos-associated apoptosis-inducing factor (AIF) nuclease (PAAN) in models of Parkinson’s; They also identify PAANIB-1 (brain-penetrant PAAN/MIF nuclease inhibitor) that prevents neurodegeneration (Click here to read more about this).
  • New research demonstrates the rejuvenating power of young CSF & identify Fgf17 as a key target; “Not only does the study imply that FGF17 has potential as a therapeutic target, but it also suggests that routes of drug administration that allow therapeutics to directly access the CSF could be beneficial in treating dementia” (Click here to read more about this and click here and here to read editorials about this research).
  • New research reports that in mice infected & recovered from SARS-CoV-2/COVID19 infection, a subsequent MPTP lesion induced a 20% greater loss of substantia nigra dopaminergic neurons (than SARS-CoV-2 or MPTP alone – click here to read more about this).
  • “We found that no astrocyte-originated dopamine neuron was generated after effective & persistent knockdown of astroglial PTBP1 either in the substantia nigra or in striatum, while AAV ‘leakage’ to nearby neurons was easily observed” – is the dream over? (Click here to read more about this).
  • New paper finds ablation of host striatal neurons resulted in reduced dopamine neuron survival within transplanted grafts, re-routing of fibres to alternate cortical targets & reduced specification of A9 neurons (Click here to read more about this).

  • New report provides an analysis of hemisphere-dependent effects of unilateral intrastriatal injection of small length α-synuclein pre-formed fibrils on mitochondrial protein levels, dynamics, & function (Click here to read more about this).
  • TRPV1 agonist capsaicin reduces phosphorylation of Parkinson’s-associated α-synuclein in primary neurons by boosting phagocytosis in PFF-tolerant microglia in vitro; “Modulating microglial metabolism might be a new therapeutic strategy for PD” (Click here to read more about this).
  • NOX2: Researchers provide evidence of NADPH oxidase 2 (NOX2) activity in the Parkinson’s brain (both microglia & neurons) & that neuronal NOX2 activation is an early phenomenon in PD animal models; Nox2 inhibitor prevents NOX2 activation in vivo (Click here to read more about this).

 

Clinical research

  • Why are humans thought to be more susceptible to neurodegeneration than equivalently-aged primates? A new biorxiv manuscript indicates that the Neanderthal contribution is unlikely to be an influential factor (Click here to read more about this).
  • Evidence of glymphatic system dysfunction in possible REM sleep behavior disorder & Parkinson’s cases; New research finds that diffusion tensor image analysis along the perivascular space provides neuroimaging evidence of glymphatic system dysfunction (Click here to read more about this).
  • A new study proposes phosphorylated α-synuclein in skin Schwann cells as a novel biomarker for multiple system atrophy (MSA); N=46 MSA (29 MSA-P and 17 MSA-C), 34 Parkinson’s, 16 dementia with Lewy bodies & 50 controls (Click here to read more about this).
  • Researchers have identified serum lipids that could significantly discriminate individuals with Parkinson’s from matched controls, as well as LRRK2 G2019S mutation carriers from non-mutation carriers (Click here to read more about this).
  • A Mendelian randomization study green tea intake & Parkinson’s progression indicates higher green tea intake was nominally associated with slower progression to depression, and lower risk of dementia, depression, hyposmia and insomnia at baseline (Click here to read more about this).

  • New research indicates that fatigue & depression in Parkinson’s may be modifiable by diet; An exploratory cross-sectional analysis of dietary & clinical data explores non-motor symptoms (Click here to read more about this).
  • A retrospective, longitudinal case-control study provides Class III evidence that electromyographic activity during REM sleep predicts the development of prodromal REM sleep behavior disorder; N=44 patients vs 44 controls; 9 developed Parkinson’s (Click here to read more about this).
  • Researchers report the results of a small randomized controlled study investigating the synergistic therapeutic effects of virtual reality based exergaming on motor & cognitive symptoms in Parkinson’s (fMRI analysis – click here to read more about this).
  • Why do some individuals avoid Parkinson’s in spite of having relatively high genetic risk? The COURAGE-PD Consortium colleagues address this question in a new report; Genetic resilience score modifies penetrance of genetic risk factors (Click here to read more about this).
  • New research suggests that “a history of depression may influence the relationship between active contact location & neuropsychological outcomes following subthalamic nucleus deep brain stimulation”; DBS & Parkinson’s (Click here to read more about this).

  • Cortical recordings (ECoG) outperform subthalamic nucleus local field potentials in decoding grip force; ‘Prediction Network Mapping’ for intracranial brain recordings in Parkinson’s; “Highlights the impact of Parkinson’s pathophysiology on the neural capacity to encode movement vigor”; “A neurophysiological & computational framework for invasive brain signal decoding to aid the development of an individualized precision-medicine approach to intelligent adaptive DBS” (Click here to read more about this).
  • New research exploring the genetic determinants influencing survival in a longitudinal cohort of 1080 Chinese patients with Parkinson’s highlights RPL3 for further research on potential role in pathogenesis (Click here to read more about this).
  • New research “refines the genetic architecture of Chromosome 4 underlying the age of onset (AAO) of the Parkinson’s phenotype through the identification of BST1 as a novel AAO PD locus” – from the COURAGE-PD consortium (Click here to read more about this).
  • Could the retinal structure of the eye be used as an early diagnostic indicator for Parkinson’s? New research involving 397 individuals with PD (+ 427 controls) indicates retinal structure is significantly altered at different clinical stages of PD (Click here to read more about this).

  • A report from OBSERVE-PD researchers examined clinical & demographic characteristics, treatment, motor/non-motor symptoms, & caregiver support of 2615 individuals identified as having advanced (vs non-advanced) Parkinson’s in 18 countries (Click here to read more about this).
  • New Biorxiv manuscript proposes a deep learning-based tool to reliably score and analyze bradykinesia for individuals with Parkinson’s; “Video-based automated analysis of MDS-UPDRS III parameters” (Click here to read more about this).
  • “We are seeing a pattern of parkinsonian phenotypes, reported following COVID19, although the available data does not yet justify a clear association between the SARS-CoV-2 pandemic and a potential rise in parkinsonism cases” (Click here to read more about this).
  • Decreased concentrations of fecal acetic, propionic, & butyric acid, & increased concentrations of plasma acetic & propionic acid are found to be associated with Parkinson’s; Fecal acetic, isobutyric, & isovaleric acid were decreased in PD cases with constipation (Click here to read more about this).
  • T lymphocyte subpopulations were profiled in 115 individuals with Parkinson’s (& 60 controls); PD cases exhibited less naïve CD8+ T (CD8+ Tn) cells & more late-differentiated CD4+ T cells; Suggests “peripheral cellular immunity is disturbed in PD” (Click here to read more about this).

  • New research provides novel insights into the atrophy progression in progressive supranuclear palsy (PSP) & offers potential utility to stratify people on entry into clinical trials, as well as track disease progression (Click here to read more about this).
  • Nigral iron is lower before the start of dopaminergic medication & then increased throughout the disease…, suggesting increased iron may not be an etiological factor”; MRI study, n=79 controls, 18 drug-naive & 87 drug-treated Parkinson’s cases (Click here to read more about this).
  • This study provides Class I evidence that statin use is associated with a lower risk of Parkinsonism in older adults (Click here to read more about this).
  • New model finds only 3 proteins (Melanoma Inhibitory Activity Protein, CRP, & albumin) can separate fast vs. slow cognitive decline subgroups in Parkinson’s (N=108 in Discovery Cohort & 83 in replication – click here to read more about this).
  • New research supports the existence of heart-brain de-synchronization in Parkinson’s with an impact on clinically relevant autonomic outcomes; A potential biomarker for early detection of central autonomic dysfunction in PD? (Click here to read more about this).
  • In contrast to a previous report, a new study finds that cross-sectional area measures of the vagus nerve (using ultrasonography) is NOT a reliable diagnostic tool in the diagnosis of Parkinson’s; N=31 PD & 51 controls (Click here to read more about this).

  • Small study, but researchers genotyped 231 Parkinson’s patients & 161 control blood donors for 6 Vitamin D receptor variants; Results “may help identify people at risk to develop PD as well as PD patients at risk” of dopaminergic treatment issues (Click here to read more about this).
  • A randomized controlled trial finds the combined effects of virtual reality techniques & motor imagery significantly improved balance, motor function & activities of daily living in individuals with Parkinson’s; N=44 (only the assessor was blinded – click here to read more about this).
  • New research provides a critical review of 35 studies applying neuroimaging to GBA-associated Parkinson’s (Click here to read more about this).
  • A retrospective case-controlled study of 1152 individuals found that early-onset dementia with Lewy bodies has clinical features that distinguish it from early-onset Alzheimer’s, but late-onset DLB features are associated with more AD co-pathology (Click here to read more about this).
  • A new Mendelian randomization study finds that there is no evidence of an association between inflammatory bowel disease & Parkinson’s across 2 separate datasets; Even subtypes (colitis & Crohn’s) have limited effect (Click here to read more about this).

  • A case report of a 60-year-old patient with a 10-year history of Parkinson’s who developed a dyskinetic-dystonic gait pattern highly impacting his personal & social life; Gait rehabilitation based on the use of visual cueing improved the situation (Click here to read more about this).
  • New research provides initial insights into peripheral LRRK2-dependent Rab phosphorylation; Measuring biobanked urine, they report higher levels of pT73-Rab10 are associated with worse Parkinson’s progression (Click here to read more about this).
  • Decoding dopamine transporter imaging for the differential diagnosis of parkinsonism using deep learning – this study involved 1017 participants (43 controls & 974 idiopathic Parkinson’s, MSA or PSP cases); Binding ratios = sign. differences between groups (Click here to read more about this).
  • A longitudinal study using deformation based morphometry examines the regional changes of brain structure during progression of idiopathic Parkinson’s; N=37 PD & 27 controls; Images acquired up to 15 time-points over observation periods of up to 8.8 years (Click here to read more about this and click here to read the press summary).
  • A protocol for the PRIME-UK cross-sectional study has been published, focused on the needs of patients with parkinsonism & their caregivers; Aim: to describe the broad range of those health needs (Click here to read more about this).

  • The first postmortem neuropathologic study of a case of Parkinson’s following focused ultrasound thalamotomy; “demyelination & neuropil loss, with many lipid-laden macrophages, but no lymphocytic infiltrates” (Click here to read more about this).
  • New study provides further evidence for a pronounced orthostatic hypotension (involvement of the autonomic nervous system) in GBA-associated Parkinson’s; From the EPIPARK Study Group (Click here to read more about this).

 

New clinical trials

  • New clinical trial registered: Denali Therapeutics & Biogen have registered the Phase 2b, randomized, double-blind, placebo-controlled (LUMA) study to determine the efficacy & safety of BIIB122 (LRRK2 inhibitor; DNL151) in 640 participants with Parkinson’s (Click here to read more about this).

  • New clinical trial registered: Neuromed IRCCS researchers have registered a small (N=20) open label Phase 4 study to evaluate efficacy of orally administrated Trehalose in individuals with idiopathic & LRRK2-associated Parkinson’s (Click here to read more about this).
  • New clinical trial registered: Annovis Bio has initiated a 6-month, placebo-controlled, double-blind Phase 3 study to evaluate efficacy, safety, & tolerability of 2 different doses their agent Buntanetap (posiphen) in 450 participants with Parkinson’s (Click here to read more about this).

  • New clinical trial registered: The “Speed Manipulated Adaptive Rehabilitation Therapy Bike for Parkinson’s Disease” (SMART) study will explore patient-specific adaptive dynamic cycling; N=40 (Click here to read more about this).
  • New clinical trial registered: Vanda Pharmaceuticals has initiated an on open-label, sequential cohorts, flexible dose 5 week study to evaluate the tolerability, safety and pharmacokinetics of Iloperidone in 24 elderly participants with Parkinson’s psychosis (Click here to read more about this).

 

Clinical trial news

  • A small clinical study exploring the effect of curcumin on idiopathic Parkinson’s – clinical & skin biopsy results; Curcumin & curcuminoid levels plasma & CSF; N=40, not a blinded study; No serious adverse events, curcumin was well tolerated for 12 months (Click here to read more about this).

  • The results of the ParkProTrain study have been published; A quasi-randomised controlled trial evaluating an individualized, tablet-based 9 month physiotherapy training programme for 230 people with Parkinson’s; Deterioration less in intervention group (Click here to read more about this).
  • The results of a randomized clinical trial exploring the use of gravity-supporting exoskeletons to improve upper extremity bradykinesia in Parkinson’s has been published; N=30, 45 min training daily, 6 days per week for 8 weeks (Click here to read more about this).
  • Pharma company UCB is recruiting participants for their “Orchestra Study”, which aims to investigate the effectiveness & safety of UCB0599 – a small-molecule α-synuclein aggregation inhibitor – in 450 people with Parkinson’s over 18 months (Click here to read more about this).

Conferences/lectures

  • Prof Alberto Espay recently spoke about “Matching therapies to people with the biology to benefit from them: the missing ingredient for successful disease modification“:

 

  • The No Silver Bullet group will be listening to Prof. Tom Foltynie who will be asking “Does the repurposing of diabetes drugs offer hope for Parkinson’s patients?” on Wednesday 29th June at 7.30 pm BST (Click here to register – it is free!).
  • The 2022 Edinburgh Parkinson’s Lecture will be held on 28th Sept 2022 and will be given by Dr Julie Jones of Robert Gordon University (Aberdeen). The lecture is entitled “The Importance of Exercise for People with Parkinson’s: Evidence, Empowerment and Enablement” (Click here to read more about this).

  • The Grand Challenger in Parkinson’s conference will be held on September 28th & 29th. The topic for this year’s meeting is Modifying Progression — From Molecules to Trials, and it will highlight recent advances that may fuel development of therapies to slow or stop disease progression (Click here to read more about this).

Other news

  • Lysogene enters an exclusive worldwide license agreement with Yeda, the commercial arm of Weizmann Institute, for a novel gene therapy candidate for neuronopathic Gaucher disease & GBA-associated Parkinson’s (Click here to read more about this).
  • NeuraLight secures $25 million in Series A to help develop their tech that tracks ALS, Parkinson’s & more with smart phone & webcam devices (Click here to read more about this).
  • Aspen Neuroscience announces $147.5M in Series B financing to help fund clinical trials of the company’s first iPSC-derived autologous dopamine neuron replacement for Parkinson’s (Click here to read more about this).

Review articles/videos

  • New review highlights where the field of Parkinson’s freezing of gait “needs to address current gaps & shortcomings including the standardization of definitions & measurement, phenomenology & pathophysiology” (Click here to read more about this).
  • Disease-modifying therapies for Multiple System Atrophy (MSA): New review provides a comprehensive overview on ongoing preclinical & clinical developments (Click here to read more about this).

  • Interesting discussion on the opportunities & counterintuitive challenges for decentralized clinical trials, in attempts to broaden participant inclusion & diversity (Click here to read more about this).
  • 10 years of milestones in tremor research gets reviewed, with a focus on the most common tremor syndromes, namely essential, dystonic, & Parkinson’s tremor (Click here to read more about this).
  • A new review provides a current perspective on the interactive roles that α-synuclein & neuroglial senescence have in Parkinson’s; Also explores the role that senolytics could play as a therapeutic avenue (Click here to read more about this).
  • Beyond neurodegeneration: What is the Parkinson’s-associated protein α-synuclein doing in red blood cells? Does it play a regulatory role during normal erythropoiesis? A new review explores these questions & asks new one (Click here to read more about this).

  • A useful commentary on the whether advanced therapeutic medicinal products (such as cell & gene therapies) can improve cognitive symptoms in Parkinson’s (Click here to read more about this).
  • New review from the “Lewy Body Dementias Clinical Trials Workgroup” explores clinical outcome measures in dementia with Lewy bodies trials; This is a critique with recommendations (Click here to read more about this).
  • A new review provides an overview on the brief history of brain iron accumulation in movement disorders, like Parkinson’s & related conditions: From first observations to recent efforts viewing extrapyramidal iron as therapeutic target & diagnostic indicator (Click here to read more about this).
  • Understanding the contributions of VPS35 & the retromer in neurodegenerative conditions (with a useful section on Parkinson’s – click here to read more about this)
  • A useful review on the convergent molecular pathways in Type 2 diabetes & Parkinson’s (Click here to read more about this).
  • Testing a drug or drug combination “in different populations defined by disease stage, histology, number of prior therapies, genetic or other biomarkers, or demographic characteristics” – a new review explores basket trials (Click here to read more about this).

  • How does deep brain stimulation change the course of Parkinson’s? – “Whether DBS is able to delay such major disease milestones or modify the progression of the disease is difficult to answer from currently published observational studies” (Click here to read more about this).
  • Researchers provide a thorough review of recent pre-clinical & clinical research on treatment strategies to sequester, degrade, or silence Parkinson’s-associated alpha synuclein (Click here to read more about this).
  • A very insightful review on the mechanisms of peripheral levodopa resistance in Parkinson’s – this covers a lot of bases; “For both forms of non-response, the first consideration should be pseudoresistance” (Click here to read more about this).

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

And there it is, just some of the highlights from May 2022 – 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 June!!!

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

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

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


2 thoughts on “Monthly Research Review – May 2022

    1. Regarding the above article, although they show that there was no conversion of astrocytes to dopamine neurons, and even explain why a previous study might have mistakenly thought that there was such conversion, they nonetheless seem to leave the door open to the possibility of such conversion if the surrounding environment (including inflammatory factors) can be improved in ways that are more compatible with such a transformation.

      “[T]he key difference between in vitro [which works–LT] and in vivo [which so far does not–LT] is the local microenvironment. Various bioactive molecules [that are] either beneficial (neurotrophic factors) or detrimental (inflammatory cytokines) existed in the local microenvironment(Janowska et al., 2019). However, under pathological conditions, these secretory factors are usually deleterious (pro-inflammatory cytokines) to the AtoN conversion process and subsequent survival, maturation of the new-born neurons. Unexpectedly, under special pathological condition like ischemia, astrocytes spontaneously initiate a potent neurogenic program after Notch signaling being repressed(Magnusson et al., 2014). Moreover, studies showed that astrocytes from different brain regions have different reprogramming efficiency and different neuron subtype preference (Grande et al., 2013; Liu et al., 2015; Hu et al., 2019; Mattugini et al., 2019). All these findings suggest that the different local environment have different impact on AtoN conversion efficiency and modulating local environment may be critical for enhancing the efficiency of AtoN conversion.

      “Therefore, only repressing PTBP1 is not enough to initiate cell fate change of astrocyte towards neuron in the mouse brain. The impact of heterogeneity of both astrocyte subtype and local environment on AtoN conversion need further inquiry in the future.”

      I wonder if the suppression of PTBP1 might be *combined* with anti-inflammatory measures to create a more favorable environment for astrocyte-to-neuron conversion…

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