Monthly research review – November 2021

# # # #

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 2021.

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

# # # #


So, what happened during November 2021?

In world news:

November 1 – American psychiatrist Professor Aaron Beck –  the father of cognitive therapy and cognitive behavioral therapy (or CBT) – passed away.

 

November 13th – The 2021 United Nations Climate Change Conference came to an ignominious conclusion with more blah-blah promises by world “leaders”, which included a “phasedown” of unabated coal power, a 30% cut in methane emissions by 2030, and plans for a halt to deforestation by 2030. And then they all hopped back on their planes and left. Perhaps in a world of zoom meetings, we can agree to “phasedown” COP conferences instead?

 

November 26 – The World Health Organization convened an emergency meeting in Geneva amid concerns over “Omicron” – a highly mutated variant of COVID-19 in South Africa that appears more infectious than Delta.

 

November 29th – Researchers presented synthetic multicellular assemblies (“xenobots”) that can replicate kinematically by moving and compressing dissociated cells in their environment into functional self-copies (Click here to read the report and click here to read a press release on the topic).

November 29th – The number of research reports on the Pubmed search engine with the keyword “Parkinson’s” climbed over 150,000. Approximately 118,000 (~80%) of them have been published since the year 2000, & 75,494 (~50%) since 2012.

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

In November 2021, there were 919 research articles added to the Pubmed website with the tag word “Parkinson’s” attached (10,965 for all of 2021 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 6 pieces of Parkinson’s news

1.  A novel progressive mouse model of PD:

Researchers report mitochondrial complex I dysfunction (MCI) alone may be sufficient to cause “a progressive, human-like Parkinsonism” in genetically engineered mice. They found that loss of MCI leads to metabolic reprogramming and resulted in progressive dopamine neuron axon dysfunction. Gene therapy (AAV-AADC) targeting the midbrain, boosted nigral dopamine release and reversed the motor deficits in the mice (Click here to read more about this and click here to read a press release).

 

2. Yumanity Therapeutics clinical trial results:

This month Yumanity therapeutics announced positive top-line results of Phase 1b clinical trial for YTX-7739 (stearoyl-CoA desaturase inhibitor) in patients with Parkinson’s. The drug was found to be safe & well tolerated over 28 days treatment. “After 28 days of treatment, the 20 mg dose given once-daily reduced the fatty acid desaturation index (FA-DI), a biomarker of stearoyl-CoA desaturase inhibition, by approximately 20%-40%, the range expected to be clinically relevant based on preclinical studies”. The company now plans to advance to Phase 2 (Click here to read more about this and click here to read an old SoPD post on this topic).

 

3. A map of mitochondrial ubiquitylation

Ubiquitylation is an enzymatic process in cells that can change the way a protein functions. This month researchers presented a global ubiquitylation analysis of mitochondria in neurons. They identified endogenous PARKIN targets following activation of PINK1, which could act as potential proxy readouts of Parkinson’s-linked mitochondrial dysfunction in future studies. They also developed an online resource to search for ubiquitin sites and enzymes in mitochondria of neurons, called MitoNUb (Click here to read more about this).

 

4.  Back from the dead? Isradipine

Post hoc re-analysis of the STEADY-PD II clinical trial results finds evidence for slowing the progression of Parkinson’s. The findings suggest that “clinically attainable brain exposure to isradipine may slow early-stage Parkinson’s progression”. “These results are consistent with the recent secondary analysis of the STEADY-PD III clinical trial”. Here is the post hoc analysis of the STEADY-PD III clinical trial (Click here to read more about this and click here to read a SoPD post on this topic).

 

5. Turn back BACH:

BACH1 is a protein that inhibits the NRF2-antioxidant pathway. New research finds that this protein is elevated in the Parkinson’s postmortem brain. Deletion of BACH1 in mice resulted in protection in a neurotoxin (MPTP) model of PD. A screening experiment identified novel benzimidazole-based molecules that can act as BACH1 inhibitors (Click here to read more about this, click here to read the press release, and click here to read a SoPD post on this topic).

 

6. More evidence for exercise:

A new study found that individuals who started physical activity after receiving their Parkinson’s diagnosis had a lower mortality rate than those who remained physically inactive. The study involved 10,699 individuals with PD and exhibited a dose-responsive association – further evidence for exercising! (Click here to read more about this).

 

# # # #

JOB ALERT: Come work at Cure Parkinson’s!

We are looking for a Research Officer (full-time role – Central London, UK) to join our research team.

Requirements:
• Science degree
• An interest in science communications
• Strong communication skills
• An interest in PPIE

Worst part of the job: You have to work with me ¯\_(ツ)_/¯

Click here to learn more about this opportunity

# # # # 

 

Articles of general interest

  • Really enjoying the Stimulating Brains podcast hosted by Prof Andreas Horn – always interesting topics related to brain & Parkinson’s research, & the recent one with Prof Julian Neumann is no exception – fascinating stuff (Click here to learn more about this)

Basic biology news

  • New research explores a physiological role of astrocytic phagocytosis of axonal debris for the medial forebrain bundle astrocytes, which may prevent the activation of microglia & spread of retrograde axonal degeneration in Parkinson’s (Click here to read more about this).
  • Researchers report that the small molecule alpha-synuclein aggregator, FN075, enhances alpha-synuclein pathology in subclinical AAV rodent models, but did not precipitate nigrostriatal degeneration or motor dysfunction (Click here to read more about this).
  • New research reports that L-DOPA & Droxidopa have the same hydrogen bond binding sites on the β2-adrenergic receptor (β2 AR) as endogenous agonists such as adrenaline, noradrenaline, & dopamine (Click here to read more about this).
  • “On the Cluster Formation of α-Synuclein Fibrils” – researchers investigated the overall structural arrangements of α-synuclein fibrils (Click here to read more about this).
  • New paper finds mitochondrial Drp1 recognizes/induces excessive mitochondrial permeability transition pore opening after hypoxia through BAX-PiC & Parkinson’s-associated LRRK2-HK2; Insights into the role of Drp1 on hypoxia-induced mitochondrial dysfunction (Click here to read more about this).

  • Conditional translating ribosome affinity purification + RNA sequencing (TRAP-seq) of Parkin interacting substrate (PARIS; ZNF746) reveals how PARIS may influence Parkinson’s-associated events by modulation of PPAR-γ associated gene clusters (Click here to read more about this).
  • New research finds that lipid peroxidation products HNE & ONE promote & stabilize Parkinson’s-associated alpha-synuclein oligomers by chemical modifications (Click here to read more about this).
  • Researchers compared mitochondrial & nuclear gene expression across regions of human brain in healthy & disease cohorts; Strong regional patterns modulated by cell-type & reflect functional specialisation; They look at Parkinson’s & Alzheimer’s & find implicated nuclear genes have non-random relationships with mitochondrial genome; Also present MitoNuclearCOEXPlorer – tool to interrogate key mitochondria-nuclear relationships in multi-dimensional brain data (Click here to read more about this).
  • New paper finds Sox6 expression distinguishes dorsally & ventrally biased nigral dopamine neurons with distinctive properties & embryonic origins; Distinctive projections to the striatum; Enriched in vulnerability pathways (Click here to read more about this).
  • New research reports that LRRK2 plays a mechanistic role in translational regulation, & the Parkinson’s-associated G2019S mutation in LRRK2 causes translational defects leading to calcium dysregulation in the mammalian brain (Click here to read more about this).

  • Staphylococcus aureus is a bacterium carried by 30–70% of general pop.; New research identifies phenol soluble modulins (functional amyloids produced by staphylococcus aureus) as catalyzer of Parkinson’s-associated alpha-synuclein aggregation (Click here to read more about this).
  • New single cell RNA seq research identifies co-regulated transcription factor module expressing ASCL1 & NEUROD1 in development of iPSC-derived dopaminergic neurons; ASCL1 = necessary transcription factor for dopaminergic selection (Click here to read more about this).
  • Ubiquitin-specific protease 10 (USP10) inhibits the dopamine-induced reactive oxygen species-dependent apoptosis of neuronal cells by stimulating the antioxidant Nrf2 activity (via increased the phosphorylation of Nrf2 activator p62 – click here to read more about this).
  • New results suggest that FOXO4 is negatively regulated in FBXO7-linked Parkinson’s – through caspase-8 activation, suppressing the cytoprotective effect of FOXO4 during 6-OHDA-induced neuronal cell death (Click here to read more about this).
  • Parkinson’s-associated α-synuclein compromised cellular calicum homeostasis & reduced lysosomal protease cathepsin D activity, but simple administration of extra Ca2+ corrected these defects ( in vitro & in drosophila – click here to read more about this).
  • New medrxiv manuscript reports a GWAS study of autopsy-confirmed Multiple System Atrophy (MSA) that identifies variants on chromosome 3 (rs16859966) located upstream ZIC1 & ZIC4 (Click here to read more about this).

  • New research finds an unanticipated function for RECS1 as a proapoptotic component of the TMBIM (transmembrane BAX inhibitor motif containing 1) family that ignites cell death programs at lysosomes (Click here to read more about this).
  • Aggregated α-synuclein induces endoplasmic reticulum fragmentation & compromises ER protein folding capacity, leading to misfolding & aggregation of immature lysosomal β-glucocerebrosidase (GCase); Parkinson’s neurons fail to initiate the UPR (Click here to read more about this).
  • New research finds that cytosolic GPR37 (but not GPR37L1) multimerization may participate in cytosolic aggregation processes implicated in Parkinson’s pathology; Can be counteracted by Parkin overexpression (Click here to read more about this).
  • Abnormal accumulation of lipid droplets in neurons induces the conversion of alpha-Synuclein to proteolytic resistant forms in a drosophila model of Parkinson’s (Click here to read more about this).
  • New report finds that CRISPR/Cas9-mediated deficiency of Parkinson’s-associated PINK1 causes similar neurodegeneration in the brains of fetal & adult monkeys as well as cultured monkey neurons without affecting mitochondrial protein expression/morphology (Click here to read more about this).
  • “Significant level of neuroinflammation in the midbrain dopaminergic system 3 weeks post mild repetitive head impact but no loss in tyrosine hydroxylase”; Mild repetitive head impacts alter perivascular flow in the midbrain – implications for Parkinson’s (Click here to read more about this).

 

Disease mechanism

  • Viral-delivered prophylactic silencing of Parkinson’s-associated α-synuclein expression in mice reduces susceptibility to motor impairments caused by synuclein pathology & prevents spreading synucleinopathy (Click here to read more about this).
  • New research indicates that microexon 34′ incorporation into TAF1 mRNA is not involved in the molecular basis of X-linked dystonia-parkinsonism (XDP) – a monogenic neurodegenerative disorder (Click here to read more about this).
  • Gain Therapeutics presented data at the Society for Neuroscience 2021 meeting on their lead molecule GT-02287, which binds to glucocerebrosidase (GCase), reduces alpha-synuclein pathology & neuroinflammation in animal models of Parkinson’s; Also rescues behaviour (Click here to read more about this).

  • New research reports long-term lactacystin injections (proteasome inhibition) in extra nigrostriatal regions did not mimic Parkinson’s path, reinforcing the vulnerability of dopaminergic neurons of the substantia nigra (Click here to read more about this).
  • Neuronal accumulation of peroxidated lipids promotes demyelination & neurodegeneration through the activation of the microglial NLRP3 inflammasome; Nlrp3 deletion rescues the neurodegenerative phenotypes in the neuronal Arf1-ablated mice (Click here to read more about this).
  • Researchers evaluated the efficacy of Alterity Therapeutic‘s ATH434 (formerly known as PBT434; an inhibitor of Parkinson’s-associated α-syn aggregation) in a mouse Multiple Systems Atrophy (MSA) model (Click here to read more about this).
  • New research reports spontaneous graft-induced dyskinesias are independent of 5-HT/serotonergic neurons & Levodopa priming in a model of Parkinson’s; “For future clinical trials, although stem-cell based therapies can be designed to be completely devoid of 5-HT neurons &, therefore, may be considered safer from a graft-induced dyskinesias perspective, our data suggest that this may not completely eliminate the risk for GIDs” (Click here to read more about this).
  • New report presents effects of GLP1-R agonists on cell transplants in a rodent model of Parkinson’s; GLP-1R agonists support survival/function, but Exendin-4 paradoxically caused insulin resistance in the grafted rats treated with L-dopa (Click here to read more about this).

  • New research reports microglia-specific overexpression of Parkinson’s-associated α-synuclein leads to dopaminergic neurodegeneration (via phagocytic exhaustion & oxidative toxicity); They used the tetracycline derivative minocycline & brain-penetrant iNOS inhibitor 1400 W to reduce the effect (Click here to read more about this).
  • New research finds that glial Nrf2 signaling mediates the neuroprotection exerted by herbal medicine-Gastrodia elata Blume in Lrrk2-G2019S Parkinson’s; Treated G2019S transgenic flies & mice exhibit behavioural improvements & cell survival; Hyperactive G2019S mutant LRRK2 enhances BMP ligand (Gbb) maturation in dopamine neurons. Secreted Gbb binds to the BMP receptor, Tkv, & turns on Mad signaling in glia. The G2019S mutation also decreases the Nrf2 activity in the brain, particularly in glia. GEB treatment restores (Click here to read more about this).
  • New research identifies small molecule inhibitors of Parkinson’s-associated α-synuclein oligomers by targeting early dopamine-mediated motor impairment in C. elegans; An antibiotic used to treat tuberculosis – called rifabutin – was validated in mammalian in vitro & in vivo systems (Click here to read more about this).
  • Researchers Vaxxinity publish preclinical work on UB-312 (one of their a-syn-immunotherapies) in the transgenic (Thy1SNCA) mice; The agent prevents motor performance deficits & oligomeric α-synuclein accumulation in the brain & gut (Click here to read more about this).

  • New study finds chronic exposure to the neurotoxin β-N-methylamino-L-alanine (BMAA) can “trigger a chain of events that recapitulate the evolution of the Parkinson’s pathology from the gut to the brain”; Is this a model of “gut first” PD?; Microbial toxins target mesencephalic mitochondria; Mouse gut microbiota is altered after oral treatment of BMAA, inducing gut dysbiosis leading to GIT impairment & inflammation; Also leads to a reduction in mesencephalic mitochondrial function (a reduction in basal & maximal respiration + a reduction in ATP synthesis – click here to read more about this).
  • New biorxiv manuscript suggests that subthalamic nucleus deep brain stimulation exerts its therapeutic effect through the disruption of STN dynamics, rather than inhibition or antidromic activation (Click here to read more about this).
  • New research finds that DA-9805 – a triple herbal extract prepared using three dried plant materials (Moutan cortex, Angelica Dahurica root, & Bupleurum root in a 1:1:1 mixture) – protects dopaminergic neurons in Parkinson’s models; from endoplasmic reticulum stress & inflammation (Click here to read more about this).
  • Researchers from Abbvie & BioArctic present preclinical findings for ABBV-0805 – a monoclonal antibody with high selectivity for human aggregated α-synuclein & very low affinity for monomers – which entered clinical trials for Parkinson’s, but then… (Click here to read more about this).

  • New data demonstrates that dynein & other autophagy proteins change with age in normal & transgenic mice & this is associated with increased α-synuclein; Could there be implications for Parkinson’s here? (Click here to read more about this).
  • New study suggests that the impact of the pathophysiology caused by misfolded Parkinson’s-associated α-synuclein spreading along the nigrostriatal pathway depends on the age of the dopamine network, (reducing striatal release specifically in adult mice – click here to read more about this).
  • New study finds long-term exposure to GDNF induces dephosphorylation of Ret, AKT, & ERK1/2, & is ineffective at protecting midbrain dopaminergic neurons in cellular models of Parkinson’s; Short-term treatment = opposite effect (Click here to read more about this).
  • New biorxiv manuscript finds repressing PTB is “incapable” of converting reactive astrocytes to dopaminergic neurons in a mouse model of Parkinson’s; “no morphologic change of astrocyte could be seen after PTB repression”; AAV “leakage” observed (Click here to read more about this).

Clinical research

  • New research used advanced diffusion MRI (NODDI, FWE-DTI) & myelin-sensitive imaging (MT-sat) to find white matter & nigral alterations in multiple system atrophy-parkinsonian type (n=21), compared to Parkinson’s (n=19) & control cases (n=20 – click here to read more about this).
  • New medrxiv manuscript provides a comprehensive analysis of the complex GBA gene using a novel algorithm for Illumina whole-genome sequence data or targeted Nanopore sequencing; Also present Gauchian – a novel bioinformatics tool (Click here to read more about this).
  • Researchers published post hoc analysis of the Nilotinib clinical trial data that suggested vascular & autophagy defects in Parkinson’s progression, and potential signs of some efficacy. Interesting, but caution required: small numbers involved (Click here to read more about this).
  • In vivo human molecular neuroimaging of dopaminergic vulnerability along the Alzheimer’s phases; Local- & system-level alterations of the mesocorticolimbic dopaminergic circuitry characterize Alzheimer’s, already in prodromal disease phases (Click here to read more about this).
  • New medrxiv manuscript explores polygenic risk prediction & SNCA haplotype analysis in a Latino Parkinson’s cohort (Click here to read more about this).

  • Speech abnormalities in early-onset & late-onset de-novo Parkinson’s share common features, but also show phenotype-specific characteristics – likely reflecting the influence of aging on the process of neurodegeneration (Click here to read more about this).
  • New medrxiv manuscript used the Michael J Fox Foundation’s Fox Insight Study data (n=35K) & found that smoking, coffee drinking & aspirin intake show an association with age at onset in idiopathic Parkinson’s; Smoking & coffee associated with increased & decreased motor scores, respectively (Click here to read more about this).
  • New research finds that dopamine genetic risk score can identify Parkinson’s patients most at risk of developing impulsive behaviors on dopamine agonist medication & predict how these behaviors may worsen over time (Click here to read more about this).
  • New research found that Parkinson’s patient with or without REM sleep behaviour disorder had similar denervation within the nigrostriatal pathway, based on VMAT2 [11C]DTBZ PET imaging (Click here to read more about this).
  • New study reports a decrease in relative T-cell numbers in Parkinson’s blood (n=36 vs 20 controls) is mostly driven by a decrease of CD8+ cytotoxic T cells & is primarily associated with the severity of the disease (Click here to read more about this).

  • Could subthalamic nucleus deep brain stimulation in Parkinson’s introduce an imbalance between the actual motor impairments & their subjective costs; Vowel production effort easier to perform with STN-DBS alone, & harder when associated with L-dopa (Click here to read more about this).
  • Researchers present neuropathological evidence of body-first vs. brain-first Lewy body disease; They use 2 postmortem datasets to argue that distribution of Lewy pathology in majority of post mortem cases seem to follow 2 patterns (Click here to read more about this).
  • Researchers report that the Parkinson’s-associated PINK1—Parkin mitophagy signaling pathway is NOT functional in peripheral blood mononuclear cells (Click here to read more about this).
  • New CSF RT-QuIC assay study in 236 Parkinson’s & 49 DLB cases finds α-synuclein ‘seeding’ in 93% of samples carrying severe GBA mutations, 78% with LRRK2 mutations, & 59% & 0% with heterozygous or bi-allelic mutations in recessive genes, respectively; 85% of PD & 86% of DLB patients showed positive RT-QuIC α-Syn seeding activity; Longitudinal analyses in 100 Parkinson’s cases demonstrate remarkably stable RT-QuIC profiles over time (up to 9 years – click here to read more about this).
  • Under-represented communities: Cross-sectional comprehensive assessment of profile & burden of non-motor symptoms in relation to motor phenotype in the Nigeria Parkinson’s disease registry cohort; “largely similar to descriptions from other populations” (Click here to read more about this).

  • Diffusion Magnetic Resonance imaging detects progression in Parkinson’s, but finds no evidence that 1 mg/day rasagiline has a disease-modifying effect over 1 year (Click here to read more about this).
  • New study suggests that from Alzheimer’s Braak stage III onward, local replication – rather than spreading between brain regions – controls the overall rate of accumulation of Tau in neocortical regions (Click here to read more about this and click here to read a press release).
  • A cohort study (N=4427) finds higher cerebral white matter hyperintensity was associated with faster progressive parkinsonism (Click here to read more about this).
  • New research finds plasma glucosylsphingosine accumulation in N370S heterozygotes carriers with & without Parkinson’s; A “clinically meaningful biomarker of GBA1-PD”? (Click here to read more about this).
  • New research explores the effects of Parkinson’s & related medications on the faecal bacterial community of 34 German PD patients (& 25 age-matched controls); Sig. higher relative abundance of Geotrichum genus in the PD samples (39.7% vs control 0.05% – click here to read more about this).

  • New study evaluated the role of dopamine in visuoperceptual accuracy versus spatial aspects of movement in idiopathic Parkinson’s (vs age-matched healthy controls); Findings support the presence of spatial deficits in early PD (Click here to read more about this).
  • New research finds a low risk of Parkinson’s in men with nonalcoholic fatty liver disease (aHR: 0.86, 95% CI: 0.82–0.91), but this in contrast to a high risk of PD in women with NAFLD (aHR: 1.09, 95% CI: 1.02–1.16); N=23k PD (10k men & 12k women – click here to read more about this).
  • Under-represented communities: The East Asian Parkinson’s Disease Genomics Consortium (EAPDGC) – a cohort of over 5500 patients in east Asia for genetic studies & also for future clinical studies (Click here to read more about this).
  • In a Danish population-based cohort study of more than 1 million persons, “cases with diabetes were in general less likely to have or to develop Parkinson’s“; No indication for diabetic retinopathy as an independent risk factor for iPD (Click here to read more about this).

  • New report presents the largest study on Glucocerebrosidase (GBA) gene variants in a multi-ethnic South-East Asian cohort with Parkinson’s; Most common variant = p.L483P; Common European risk variants p.E365K, p.T408M, & p.N409S not detected (Click here to read more about this).
  • New medrxiv manuscript presents a 30 second quantitative digitography-repetitive alternating finger tapping task, algorithmically analyzed in real time, providing quantitative metrics of Parkinson’s (Click here to read more about this).
  • In this study exploring neuron-specific enolase level as a potential biomarker for distinguishing amyotrophic lateral sclerosis (ALS) from cervical spondylotic myelopathy, there are some analyses of Parkinson’s cases with several outliers (Click here to read more about this).
  • A pilot study proposes exosomal miRNA as peripheral biomarkers in Parkinson’s & progressive supranuclear palsy (PSP); Exosomal levels of miR-21-3p, miR-22-3p & miR-223-5p discriminated PD from controls; miR-425-5p, miR-21-3p, & miR-199a-5p = PSP vs PD (Click here to read more about this).
  • New data from a LRRK2-Parkinson’s cohort treated with deep brain stimulation; Earlier age of onset and dyskinesia; STN and GPi DBS targets effective; Longer disease duration; Medication reduction favored the STN group (Click here to read more about this).

  • Simple bedside tests of attention & arousal at a single visit may accurately detect delirium in Parkinson’s, dementia & elderly controls, but the optimal tests differed between groups (Click here to read more about this).
  • A study explores real-world study of wearable sensors (5 sensors, one on each limb & on the trunk with cloud-based web portal) in Parkinson’s; “Gait activity is reduced in individuals with PD in their natural environment” (Click here to read more about this).
  • Cerebrospinal fluid biomarker analysis in Parkinson’s with freezing of gait (FOG) finds that the anti-inflammatory marker, fractalkine, is significantly decreased in PD & further decreased in PD-FOG compared to PD-No-FOG (Click here to read more about this).
  • Nigral diffusivity, but not free water, correlates with iron content in Parkinson’s; No relationship was observed in this study of 2 cohorts (n=181) between iron & the free water compartment in substantia nigra (Click here to read more about this).
  • A new case report has been published on an early-onset parkinsonism linked to complex heterozygous mutations involving both the PANK2 & PLA2G6 genes in a Chinese woman (Click here to read more about this).
  • A nationwide retrospective cohort study in South Korea reports cholecystectomy (surgical removal of the gallbladder; 2010 to 2015; n = 161,838) is associated with an elevated risk of Parkinson’s (vs the control group n = 286,135); Gender results differed (Click here to read more about this).

  • Dopaminergic therapy for motor symptoms in early Parkinson’s disease practice guideline summary” (Click here to read more about this).
  • Glucosylceramide in cerebrospinal fluid of patients with GBA-associated & idiopathic Parkinson’s disease enrolled in the PPMI study; N=411 of which 44=GBA-PD; GlcCer/SM ratio as a potential stratification tool for clinical trials of iPD (Click here to read more about this).
  • Prism adaptation is a sensory-motor shift after the visual field has been artificially shifted; A double-blind randomized controlled trial reports that 2 weeks of twice-daily prism adaptation treatment does not improve posture or gait in Parkinson’s (Click here to read more about this).
  • New study (n=987) proposes plasma concentrations of plasma p-tau181 & p-tau23 have the potential to act as a cost-effective & accessible biomarker of Alzheimer’s pathologic characteristics & as a prognostic marker of dementia with Lewy bodies (Click here to read more about this).
  • A new meta-analysis on cholinesterase inhibitors for gait, balance, & falls in Parkinson’s provides more evidence for potential benefits (Click here to read more about this).
  • Could genetic factors be contributing to the heterogeneity of dopaminergic deterioration during the premotor stage of Parkinson’s? New report presents findings from 2 databases; Dopamine dysfunction in PD appears to start about 10 yrs before motor onset (Click here to read more about this).

 

New clinical trials

  • New clinical trial registered: A long-term follow up has been registered for the a1-adrenergic blocker terazosin pilot study in 15 individuals with pre-motor Parkinson’s/RBD; Assessments every 6 months for 3 years (Click here to read more about this).
  • New clinical trial registered: CuraSen Therapeutics have initiated a 14 day Phase II study of CST-2032 (a brain-permeant, selective adrenoceptor modulator) administered with CST-107 on mild cognitive impairment due to Parkinson’s or Alzheimer’s (Click here to read more about this).

  • New clinical trial registered: Addex Therapeutics have an open-label safety study of Dipraglurant (ADX48621) – a negative allosteric modulator of the mGlu5 receptor – in individuals with Parkinson’s receiving L-dopa-based therapy (Click here to read more about this).

 

Clinical trial news

  • Abbvie‘s subcutaneous, pump-delivered levodopa-carbidopa formulation ABBV-951 scores a goal in Phase III for Parkinson’s; A 2.7-hour increase in “On” time; Planned approval filings (Click here to read more about this).
  • FAScinate Therapeutics submits their Investigational New Drug (IND) application for Phase 2 clinical studies of their FAF1 inhibitor KM-819 for Parkinson’s; FAScinate is a subsidiary of Kainos Medicine Inc (Click here to read more about this).

  • Insightec announced today that the US FDA has approved the Exablate® Neuro (focused ultrasound) for treating advanced Parkinson’s patients suffering from mobility, rigidity, or dyskinesia symptoms (Click here to read more about this).
  • The results of the “Effects of Resistant Starch on Bowel Habits, Short Chain Fatty Acids & Gut Microbiota in Parkinson’s Disease” (RESISTA-PD) have been published – an 8-week prebiotic intervention with resistant starch involving 82 participants (Click here to read more about this).

 

Conferences/lectures

  • The No Silver Bullet for Parkinson’s Support group have invited Lucy Jung, CEO of Charco Neurotech to speak at their next virtual meeting on Monday 13th December at 8 pm (London time – click here to learn more about this).

 

Other news

  • Ventus Therapeutics will be presenting data for their NLRP3 inhibitor program at the 3rd Inflammasome Therapeutics Summit on 16-18 November; They have NLRP3 inhibitors being developed for neurological indications, like Parkinson’s (Click here to read more about this).
  • Biotech firms Artizan Biosciences & Biohaven Therapeutics announce a therapeutic development program to leverage Artizan’s biobanking expertise & proprietary drug discovery engine to create Parkinson’s drug development program (Click here to read more about this).

 

Review articles/videos

  • “Entrepreneurial treatment activism for undone science: mannitol & Parkinson’s” – can crowd science plug the holes in ‘undone science’? The authors explore the example of Clinicrowd (Click here to read more about this).

  • They had me with Charlotte Haley… Lots of really interesting ideas & thoughts on an environmental agenda for preventing Parkinson’s; “Though not exhaustive, the “Parkinson’s prevention agenda” builds upon many years of research by our colleagues and proposes next steps through the lens of modifiable risk factors”; Identifying 10 specific areas of further inquiry (Click here to read more about this).
  • American stem cell sell in 2021: U.S. businesses selling unlicensed & unproven stem cell interventions – “More than 4x as many businesses than were identified 5 yrs ago are selling stem cell products that are not FDA-approved & lack convincing evidence” (Click here to read more about this).
  • “Some readers might be surprised that the FDA is paid by Pharma—that the very industry the FDA has a duty to regulate supplies 65% of its budget used for the drug approval process” – Dr Nancy Olivieri does not hold back on aducanumab & the FDA (Click here to read more about this).
  • “Waiting for PARIS” – a commentary on recent Parkinson’s research exploring the inhibition PARIS with farnesol (Click here to read more about this).

  • New review on some of the basic research leading through to clinical applications targeting lysosomes in human conditions; Parkinson’s gets a small mention (nothing on ambroxol), but very useful overview of lysosomal biology (Click here to read more about this).
  • “Cal‘MAM’ity at the endoplasmic reticulum-mitochondrial interface“; A useful review of a potential therapeutic target for neurodegeneration (Parkinson’s gets a mention) & human immunodeficiency virus-associated neurocognitive disorders (Click here to read more about this).
  • A comprehensive review of glycosphingolipid metabolism & its role in ageing + Parkinson’s; Interesting discussion on the mechanisms by which changes can affect neurodegeneration (Click here to read more about this).
  • Nice in focus piece looking back at the Parkinson’s research paper that started it all: The discovery of alpha synuclein in Lewy pathology of Parkinson’s (Click here to read more about this).

  • A nice in focus piece exploring the origins of the protein spread theory of Parkinson’s (Click here to read more about this).
  • Often mistaken for Parkinson’s, “Essential tremor is one of the most common movement disorders, with a reported >60M affected individuals worldwide”; This is a wonderful primer on the condition- lots of bases covered (Click here to read more about this).
  • New review on HMGB1 as a potential & challenging therapeutic target for Parkinson’s; Explores the difficulties of distinguishing between ‘good’ & ‘bad’ HMGB1 (Click here to read more about this).
  • New mini review on the role of cleaved PINK1 in neuronal development, synaptogenesis, & plasticity: Implications for Parkinson’s? (Click here to read more about this).
  • The case for c-ABL inhibition in disease modification for Parkinson’s; “Nilotinib reached only a maximum of 10% of the concentration thought to be required for adequate inhibition of c-Abl” (Click here to read more about this).

  • A useful new review article on gastrointestinal mucosal biopsies in Parkinson’s goes beyond alpha-synuclein detection & explores additional opportunities (such as potential use of single-cell & spatial transcriptomic technologies – click here to read more about this).
  • New review of TLR2 & TLR4 in Parkinson’s proposes model in which microbial dysbiosis alters permeability of the intestinal barrier as well as TLR2 & TLR4 signaling; Leads to a +ve feedback loop of chronic gut dysfunction promoting α-synuclein aggregation (Click here to read more about this).
  • A useful review on the JAK/STAT signaling pathway; Covers a lot of bases all the way from the bench to clinic; Includes a short section on Parkinson’s; In particular, there is a very good section on the available therapeutics targeting this pathway (both clinical & experimental), including the various approaches & the ongoing clinical trials (Click here to read more about this).
  • A useful review on NRF2 activation & downstream effects, with a focus on Parkinson’s & brain angiotensin; “The relationship between AngII signaling & NRF2 has been shown to be quite complicated” (Click here to read more about this).

  • A useful review of O-GlcNAcylation in health & neurodegenerative conditions (a good section on Parkinson’s – click here to read more about this).
  • A new review looks at efforts to move certain blood-based biomarkers into the clinic for Alzheimer’s (Click here to read more about this).

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

And there it is, just some of the highlights from November 2021 – another very busy month of Parkinson’s research. Hopefully there will be bits and pieces of interest for everyone in the list. Much of the material used here was collected from the Science of Parkinson’s Twitter feed (and there is a lot more posted there each day).

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

And now: on to December!!!

All of the material on this website is licensed under a
Creative Commons Attribution 4.0 International License
You can do whatever you like with it!


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

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

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


Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Google photo

You are commenting using your Google account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s

This site uses Akismet to reduce spam. Learn how your comment data is processed.