Monthly research review-April 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 April 2022.

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

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So, what happened during April 2022?

In world news:

April 4th – The Intergovernmental Panel on Climate Change (IPCC) released the third and final part of its Sixth Assessment Report on climate change, warning that greenhouse gas emissions must peak by 2025 at the latest and decline 43% by 2030, in order to limit global warming to 1.5 °C (2.7 °F).

 

April 14th – Ignominious stuff: The Russian Black Sea Fleet flagship Moskva became the largest warship to be sunk in action since World War II.

 

April 22nd – The Large Hadron Collider recommenced full operations, three years after being shut down for upgrades.

April 25th – The social media network Twitter accepted a buyout offer from Tesla and SpaceX CEO Elon Musk for $44 billion (that amount would fund a lot of Parkinson’s research and community nurses… just saying…)

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

In April 2022, there were 1006 research articles added to the Pubmed website with the tag word “Parkinson’s” attached (4418 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.  It’s not just dopamine:

German researchers reported that GABAergic neurons (generated by CRISPR-mediated direct in vivo reprogramming of striatal astrocytes) rescues voluntary motor behavior in a neurotoxin-induced mouse model of Parkinson’s. The reprogramming factors involved were Ascl1, Lmx1a, & Nr4a2. Two different investigative approaches have been used, and in both systems, a significant reduction of motor impairments was observed. The reprogrammed neurons did not acquire dopaminergic fate, suggesting “a novel intervention strategy beyond the restoration of dopamine levels” (Click here to read more about this).

2.  The liraglutide results:

The initial results of the Phase 2 clinical trial exploring the diabetes medicine liraglutide in Parkinson’s were announced. In this Cure Parkinson’s supported study, the investigators found that 1 year of treatment with this drug resulted in improvements in non-motor symptoms, activities of daily living and quality of life measures. These encouraging insights into the effectiveness of this class of treatment builds on an increasing collection of data pointing towards GLP-1 receptor agonists as a useful new treatment for PD (Click here to read more about this and click here to read a SoPD post about this topic).

3.  Taking the sting out of PD:
New research provided further support for the innate immune cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) DNA-sensing pathway being involved in Parkinson’s. The researchers reported (both in vitro & in vivo) that preformed aggregates of the Parkinson’s-associated protein alpha synunclein stimulates STING-dependent neuroinflammation & dopaminergic neurodegeneration. Mice that are STING-deficient were protected from this alpha synuclein-induced dopaminergic neurodegeneration. In addition, STING protein was found to be elevated in the brains of people with Parkinson’s (Click here to read more about this).

4. The UK Parkinson’s Disease Clinical Studies Group:

The UK Parkinson’s Disease Clinical Studies Group (UK PD-CSG) was launched this month. The group has been set up to develop and support Parkinson’s clinical research across the UK, with a special emphasis on studies exploring disease modification. In addition, the organisation will be encouraging patient education and engagement, as well as the training of future generations of researchers.

 

5. New tools and the genotoxic stress of PD

Researchers presented a virus-based system that can function as a single-cell genetic sensor (which they called “PRISM“) to allow for the detect of brain “genotoxic stress” and visualise neurodegeneration in genetically engineered mouse models of Parkinson’s. It’s a powerful new tool for preclinical research, but of particular interest at the end of their study, they presented post mortem brain analysis from Parkinson’s cases that confirmed loss of nigral melanized neurons is less than the loss of TH+ neurons (indicating the survival, but loss of function of some dopamine neurons), AND they reported that the total melanized neurons labelled with γH2AX (a marker of DNA breaks) in the PD group (40.7%) was significantly higher than controls (25.6% – Click here to read more about this).

 

Articles of general interest

  • “Developing a CNN for Diagnosis”: Teenage age siblings develop a handwriting-recognition AI for detecting Parkinson’s – definitely a pair to watch! (Click here to read more about this).
  • Another one to watch: Dr Kevin McFarthing on drug research and development for Parkinson’s:
  • A call to action on including people with Parkinson’s in clinical study design & execution – it gives a strong ‘why’ & addresses the challenges while offering solutions to consider; “Importantly, systematic identification of certain barriers & facilitators for active patient engagement & finding solutions on how to remove barriers is greatly needed to further develop the guiding principles for effective patient researchers in Parkinson’s” (Click here to read more about this).
  • 12 stories of individuals with Parkinson’s & their journeys to end the disease through prevention, advocacy, care & treatment:

 

Basic biology news

  • NeuroSCORE: A genome-wide omics-based model to identify candidate genes associated with conditions of the CNS; Combining multiple genome-wide databases, 5 metrics independently associated with genes assoc. with CNS-related conditions (Click here to read more about this).
  • Arginylation = post-translational modification where proteins are modified by the addition of arginine at the N-terminal amino group; New research suggests α-synuclein arginylation may constitute a potential neuroprotective mechanism in Parkinson’s (Click here to read more about this).
  • New tongue-twister: “Mitolysosome exocytosis” – Flunarizine, a drug whose chronic use is associated with Parkinsonisms, found to induce mitochondrial dysfunction + decreased mitochondrial mass & content (in neurons & astrocytes), without affecting the number of dopamine neurons (Click here to read more about this).

  • Curious: Dopamine neurons release GABA via unconventional mechanism. Researchers report that membrane GABA transporters & VMAT can “respectively substitute for Gad-dependent GABA synthesis & Vgat-mediated vesicular loading” (Click here to read more about this).
  • New report finds in utero gammaherpes virus infection in mice = midbrain transcriptomic & methylation changes in 8-wk-old offspring; Could maternal infection increase the risk of later Parkinson’s? (Click here to read more about this).
  • New paper presents a neuronal assay for investigating the protective efficacy of α-Syn antibodies; They find stability of antibody-α Syn complexes may be more important for conferring protection than binding epitope or affinity (Click here to read more about this).
  • Researchers report cells with Parkinson’s-associated PARKIN variants exhibit deficits in the mitochondrial biogenesis pathway, resulting in mtDNA dyshomeostasis; Postmortem data supports + increased microglia proinflammatory cytokines (Click here to read more about this).
  • New research presents a small aromatic compound, “SynuClean-D”, which inhibits the aggregation & seeded polymerization of multiple α-synuclein strains (Click here to read more about this).
  • Researchers report that defective mitochondria in Pink1 mutant flies activate Relish targets & demonstrate that inflammatory signaling causes age-dependent intestinal dysfunction, metabolic reprogramming & neurotoxicity (Click here to read more about this).

  • New research provides an atlas of transcriptionally defined cell populations in the rat ventral tegmental area; Single-nucleus RNA sequencing on 21,600 cells highlights the heterogeneity of the rat VTA (Click here to read more about this).
  • Researchers present new data indicating that phosphorylated alpha-synuclein is increased in the GBA1-D409V KI x mThy1-hSNCA mouse, but pathology is not increased in the Syn PFF injection model with GBA1-D409V KI (Click here to read more about this).
  • Transcriptomic & regulatory network analyses on the cingulate cortex from individuals with Parkinson’s finds “myelin genes & the oligodendrocyte development pathways were markedly downregulated” (N=8 vs 8 controls – click here to read more about this).
  • Scientists combine nanoscale imaging, chemical spectroscopy, & atomic-scale modeling to construct a detailed picture of the assembly of Parkinson’s-associated α-Synuclein proteins in the presence & absence of copper ions (Click here to read more about this).
  • New biorxiv manuscript questions the prion-disease hypothesis of Parkinson’s & proposes that endocytosed alpha synuclein impairs the host cell′s mitochondrial function; “Toxicity of extracellular a-syn is independent of intracellular a-syn” (Click here to read more about this).
  • Astrocytes & oligodendrocytes have altered & heterogeneous transcriptomes in Alzheimer’s; “Dataset integration improves glia clustering & suggests putative altered function” (Click here to read more about this).

  • New biorxiv manuscript investigates 98 variants in Parkinson’s-associated LRRK2; These “findings will aid in understanding the impact of these variants on LRRK2 kinase activation, stimulate work to reveal mechanisms by which variants impact biology, & provide rationale for variant carrier inclusion or exclusion in ongoing & future LRRK2 clinical trials” (Click here to read more about this).
  • Researchers report plasma autoantibodies to glial fibrillary acidic protein (GFAP) react with brain areas according to Braak staging of Parkinson’s; Highest in dorsal motor nucleus vagus & lowest in frontal cortex areas (Click here to read more about this).
  • Previous studies have reported SIRT2 knockout protecting models of Parkinson’s; Now researchers find that Cdk5 phosphorylation-induced SIRT2 nuclear translocation can promote neuronal death (Click here to read more about this).
  • A new biorxiv manuscript reports increased levels of glucosylsphingosine (GlcSph, but not glucosylceramide (GlcCer)) in the CNS & serum in GBA1+/L444P mice – plus formation of hippocampal alpha-synuclein inclusions (Click here to read more about this).
  • New research reports Zika virus infection triggers Alzheimer’s-associated features in brain organoids: increase in Aβ & p-Tau levels, plus endoplasmic reticulum stress & unfolded protein response. PERK inhibition attenuates the effect (Click here to read more about this).

  • Pyruvate dehydrogenase kinase (PDK) protects dopaminergic neurons from oxidative stress in the DJ-1 mutant fly model of Parkinson’s; PDK phosphorylates & inhibits the PDH complex; CPI-613, an inhibitor of PDH, also protected DJ-1 null flies (Click here to read more about this).
  • In flies, Prostaglandin A2 interacts with Nurr1, which ameliorates the behavioral deficits & neuronal degeneration observed in LRRK2 G2019S transgenic fly model of Parkinson’s (Click here to read more about this).
  • Administration of methylglyoxal (a glycating agent) to Thy1-alpha Synuclein transgenic mice accelerates Parkinson’s-like sensorimotor & cognitive alterations; Increased glutamatergic signaling may underlie these events; The “study sheds new light into the enhanced vulnerability of the midbrain in Parkinson’s-related synaptic dysfunction & suggests that glycation suppressors & anti-glutamatergic drugs may hold promise as disease-modifying therapies for synucleinopathies” (Click here to read more about this).
  • “Wild type & Parkinson’s-related truncated α-Syn can co-exist in the condensates. The truncated α-Syn could dramatically promote WT α-Syn phase separation… the truncated α-Syn accelerated WT α-Syn turning to amyloid aggregates by modulation of phase separation” (Click here to read more about this).
  • New paper reports a NAC domain mutation (E83Q) in Parkinson’s-associated alpha synuclein that unlocks its pathogenicity & recapitulates its pathological diversity; Higher seeding activity + LB-like inclusions (Click here to read more about this and click here to read a press summary of this research).
  • Synaptic vesicle binding of Parkinson’s-associated α-synuclein is modulated by β- & γ-synucleins; They form heteromultimers with α-syn, which reduces synaptic vesicle binding of α-synuclein in a concentration-dependent manner (Click here to read more about this).

  • New research presents a combination of lipidomic & machine learning analyses that reveal alterations in glycerophosphatidylcholine & triradylglycerol in sera from Parkinson’s cases (& cells & tissues expressing mutant α-Syn – Click here to read more about this).
  • Researchers present “clearing-assisted tissue click chemistry” (or CATCH) – an in situ fluorescence imaging method of target-bound drug molecules at subcellular resolution that enables the identification of targets in intact mammalian tissues (Click here to read more about this).
  • Using a protein mimetic approach (Foldamers), researchers have identified α-Synuclein sequences-based targets that are essential for aggregation & may have therapeutic implications in Parkinson’s (Click here to read more about this).
  • New research proposes that the Parkinson’s-associated A53T mutation & C-terminal truncation enhance α-syn aggregation by reducing unfavorable activation enthalpy of nucleation, & triggering the autocatalytic fibril elongation on the fibril surfaces (Click here to read more about this).

Disease mechanism

  • Researchers from Asceneuron present their O-GlcNAcase inhibitor, ASN90, as a multimodal drug candidate for Tau & α-Synuclein proteinopathies; It slows progression of motor impairment & reduced astrogliosis in an α-syn rodent model of Parkinson’s (Click here to read more about this).

  • New paper reports Parkinson’s-associated alpha-synuclein can reduces NMNAT3 levels & neurite formation; Rescued by targeting the NAD+ pathway; NMNAT3 is reduced in the PD caudate nucleus, inversely correlated with α-syn (Click here to read more about this).
  • Further evidence demonstrating the neuroprotective potential of GM1 in models of Parkinson’s. GM1 ganglioside modifies microglial & neuroinflammatory responses in a rodent AAV-A53T α-synuclein model of PD (Click here to read more about this).
  • At the 2022 annual meeting of the American Academy of Neurology there is a presentation on exposure to β2-adrenoreceptor (β2AR) agonists & how they (particularly ultra-long-acting β2AR agonists) may be associated with a reduced risk of developing Parkinson’s (Click here to read more about this).
  • Researchers report that the deubiquitinase cylindromatosis (CYLD) is a regulator of PARIS protein stability; Knockdown of CYLD in multiple PINK1 & parkin models of Parkinson’s attenuates PARIS accumulation & neurotoxicity (Click here to read more about this).
  • Researchers from Yumanity Therapeutics present new preclinical data on the brain-penetrant stearoyl-CoA desaturase inhibitor, YTX-7739; Reduces pathology in A53T & α-Synuclein triplication patient-derived neurospheres, & E46K α-Synuclein Parkinson’s mouse model (Click here to read more about this).

  • Researchers report that 1 month of Stearoyl-CoA Desaturase inhibition reverses immune, synaptic & cognitive impairments in a mouse model (3xTg) of Alzheimer’s; Brain fatty acid metabolism links AD genes to downstream effects (Click here to read more about this).
  • Researchers (including scientists from FUJIFILM Cellular Dynamics) present preclinical optimizing maturity and dose of iPSC-derived dopamine progenitor cells for transplantation therapy for Parkinson’s; No teratoma formation or significant overgrowth. “Now it will be important to design refined clinical neurosurgical protocols & immunosuppression regimens to achieve the full clinical benefit that is possible to attain with dopamine cell replacement therapy in carefully selected groups of Parkinson’s patients” (Click here to read more about this).
  • Analogue of Cholecystokinin promotes dopamine neuron survival (via activation of the cAMP/PKA/CREB pathway) in a MPTP mouse model of Parkinson’s; Decreased glia activation & neuroinflammation, plus improved autophagy dysfunction; Liraglutide was the comparator (Click here to read more about this).
  • New research presents the design, synthesis, & biological assessment of potent 20S proteasome activators; This class of compounds prevented the accumulation of Parkinson’s-associated A53T α-syn (in vitro – Click here to read more about this).
  • New research explores whether L-DOPA impacts on survival & functional recovery of hESC-derived dopaminergic neurons following grafting into models of Parkinson’s; Early improvements in L-DOPA-induced dyskinesia (Click here to read more about this).
  • New biorxiv manuscript demonstrates that graft-host integration, & not DA neuron content, is a key consideration to graft-induced functional recovery in models of Parkinson’s (Click here to read more about this).
  • Omarigliptin (a long-acting oral antidiabetic drug of the DPP-4 inhibitor) attenuates rotenone-induced rat model of Parkinson’s (via antioxidant & anti-inflammatory effects – click here to read more about this).

Clinical research

  • Could tracking the appearance of new/emergent symptoms over time be used as a measure of progression in early Parkinson’s? New data indicates yes (from STEADY-PD dataset – click here to read more about this).
  • New research combines genomic, transcriptomic & neuroimaging data with the purpose of identifying individually tailored interventions Parkinson’s patients (using PPMI data from 294 cases – click here to read more about this).
  • Researchers find “a higher consumption of large amounts of saturated fat might be associated with an increased risk of Parkinson’s. A diet low in saturated fat might be beneficial for disease prevention“; Used the Swedish National March Cohort data set (Click here to read more about this).
  • New research finds significantly increased iron deposition in the substantia nigra & FDG-uptake in the putamen + reduced functional connectivity between the substantia nigra & putamen in patients with Parkinson’s (vs controls); Highlights utility of simultaneous PET/MRI (Click here to read more about this).
  • Lewy bodies in the brains of children??? “Nanoparticles could serve as a common denominator for misfolded proteins & could play a role in altering & obstructing nuclear pore complexes”. Could early life air pollution pose a risk for later Parkinson’s? (Click here to read more about this).
  • New study does not “support the notion that APOEε4 is an independent driver of α-synuclein pathology in pure dementia with Lewy bodies, but rather implicate GBA as the main risk gene for the pure dementia with Lewy bodies subgroup” (Click here to read more about this).

  • There are many reports of hyper inflammatory state in Parkinson’s, but a new biorxiv manuscript suggests that this hyper-responsiveness does not apply to antigen-specific T cell responses to many common antigens (Click here to read more about this).
  • Small study, but results indicate Parkinson’s patients with higher α-synuclein extracellular vesicles in their plasma had a higher UPDRS III; Poly (ADP-ribose) detected in 35% of discovery cohort, but not signif. in replication cohort (Click here to read more about this).
  • ADCY5-related dyskinesia currently has no validated treatment; A retrospective study on 30 ADCY5 mutation carriers who had tried caffeine for dyskinesia finds 87% of participants reported “a clear improvement” (Click here to read more about this).
  • Analysis of a longitudinal study (Parkinson’s N=152; controls N=52) found that baseline detection of cerebrospinal fluid β-amyloid predicted decline for memory; ApoE genotype effect reported; β-amyloid as a prognostic biomarker for cognitive changes in PD? (Click here to read more about this).
  • A sensor-based analysis demonstrates the difficulties in identifying consistent early subtle gait abnormalities in asymptomatic carriers of the Parkinson’s-associated LRRK2-G2019S mutation (Click here to read more about this).
  • A useful teaching tool on the “Faces of Parkinson’s”: Helping students realize it is more than tremors; “Educators must realize that adult students who are unfamiliar with subject matter may not find the content relevant” (Click here to read more about this). And here is the Michael J Fox Foundation video of the same title that is mentioned in this report. Michael J Fox interviewers 5 people who are affected by the condition:
  • “We propose striatal dopaminergic terminal loss measured using 123I-ioflupane SPECT & nigral dopamine neuron loss assessed with NM-MRI as early-stage & advanced-stage motor impairments biomarkers, respectively”; Motor progress. & neurodegeneration in Parkinson’s (Click here to read more about this).
  • Could elevated phase-amplitude coupling in the primary motor cortex indicate higher probability of freezing? New study suggests yes & DBS alleviates freezing by both decoupling cortical oscillations & enhancing cortical resistance to abnormal coupling (Click here to read more about this).
  • Researchers aimed to explore plasma branched-chain amino acids & aromatic amino acids profiles in a Parkinson’s cohort (n=106 PD & 114 controls); They found decreased BCAAs & tyrosine levels in PD (particularly advanced cases); Gut microbial amino acid metabolism? (Click here to read more about this).
  • A longitudinal study (using deformation based morphometry) explores regional changes of brain structure during progression of idiopathic Parkinson’s; Highlights occipital & temporal lobes, inferior parietal lobule, plus insula, putamen & n. basalis Meynert. The researchers report “the observed longitudinal patterns of accelerated volume decrease in Parkinson’s patients largely coincide with the pattern of α-synuclein pathology in PD stages 3–5 as proposed by Braak & colleagues” (N=37 PD vs 27 controls – click here to read more about this).
  • In a cohort of 195 Parkinson’s patients (27 with diabetes) from the Biomarkers in PD (MARK-PD) study, diabetes & high HbA1c were associated with increased neuroaxonal damage & cognitive impairment; Also increased serum NfL levels & decreased MoCA scores (Click here to read more about this).

  • Research provides Class II evidence that serum neurofilament light levels are associated with incident Parkinson’s, parkinsonian signs, & physical functioning decline; N=1,327 from Chicago Health & Aging Project (CHAP – click here to read more about this).
  • New data shows how dopamine treatment differentially augments thalamic GABA concentrations in Parkinson’s – may modify impulsivity; They see a blunted thalamic GABA response to dopamine agonists in patients with elevated impulsivity (Click here to read more about this).
  • A gender gap in deep brain stimulation for Parkinson’s. New study provides Class II evidence of beneficial effects of deep brain stimulation in women with Parkinson’s (compared to male controls), & points to gender differences throughout the DBS process (Click here to read more about this).
  • Forget Roblox! NeuroOrb – all the cool kids are doing it! Researchers present the NeuroOrb Gaming System – designed specifically for use with people who have motor impairments; Pilot studies in individuals with Parkinson’s (Click here to read more about this).
  • Researchers evaluate the direct medical cost, drug utilization & expenditure for managing Parkinson’s at a medical center in China; “Drug costs accounted for 97.82% & 23.33% of the total direct medical expenditure for out- & inpatients.., respectively” (Click here to read more about this).
  • The Spain PD consortium researchers report smoking is associated with a lower mean age at Parkinson’s onset; Also they found that APOE genotype was not associated with age at PD onset; Cohort N=753 (Click here to read more about this).

  • Could mild cognitive impairment in isolated REM sleep behavior disorder (iRBD) be a predictor of phenoconversion to Parkinson’s or Dementia with Lewy bodies? New research (N=40 iRBD, including 21 with MCI; Plus 19 controls) provides support (Click here to read more about this).
  • New report finds a specific frontoparietal causal signaling pathway from right middle frontal gyrus to right posterior parietal cortex impairment in some Parkinson’s cases; Dopaminergic medication reinstates the relation with working memory performance (Click here to read more about this).
  • Researchers propose a composite clinical motor score (combining the MDS-UPDRS III, Purdue Pegboard Test & Timed Up and Go) as a comprehensive & sensitive outcome measure for Parkinson’s (Click here to read more about this).
  • New research used automated machine learning on multimodal data (PPMI dataset) to make improved multi-omic predictions of Parkinson’s; Shifting the “paradigm of focusing on a single biomarker” (Click here to read more about this).
  • How genetic variants may influence changes in the brain over time – Longitudinal MRI data from 15,640 individuals were used to compute rates of change for 15 brain structures; Study identifies variants involved in structural CNS changes (Click here to read more about this).
  • REM sleep behavior disorder (RBD) is viewed as a prodrome for PD. Now, researchers propose 4 types of early probable RDB evolution patterns, which feature different brain pathology & predicted different courses of motor & cognitive decline in Parkinson’s (Click here to read more about this).

 

 

  • New research compares serum metabolites, gut bacterial community composition, & clinical variables in 63 individuals with Parkinson’s (vs 61 controls); 139 metabolite features predictive between PD & controls (Click here to read more about this).
  • Small study, but researchers identify 3 subgroups of idiopathic Parkinson’s mainly characterized by gender, DRD2 Taq1A (rs1800497) polymorphism & disease progression (Click here to read more about this).
  • Development & validation of automated magnetic resonance Parkinsonism index 2.0 to distinguish Progressive Supranuclear Palsy-Parkinsonism (PSP) from Parkinson’s (Click here to read more about this).
  • Can we diagnose Parkinson’s by investigating the inhibitory effect of serum components on P450 inhibition assay? New study presents data from rodent models of PD & from sera collected from patients with PD (vs controls – Click here to read more about this).
  • New research finds free water & free-water-corrected diffusion tensor imaging can index cholinergic degeneration in Parkinson’s – potential for stratifying patients in clinical trials of cholinergic interventions (Click here to read more about this).
  • Researchers report gait abnormalities & non-motor symptoms predict abnormal dopaminergic imaging in presumed drug-induced Parkinsonism (DIP); N=34 US veterans with DIP (Click here to read more about this).
  • Time to start conducting Parkinson’s clinical trials in the “metaverse”? (remote & more fun than the clinic) This study highlights some of the potential: A fully-immersive virtual reality setup to study gait modulation (Click here to read more about this).

 

New clinical trials

  • New clinical trial registered: Mayo Clinic researchers will be evaluating extended-release melatonin in 50 individuals with Rapid Eye Movement Sleep Behavior Disorder (RBD – click here to read more about this).
  • New clinical trial registered: Celon Pharma has initiated a Phase 2 efficacy, safety & pharmacokinetic study of CPL500036 (a PDE10A inhibitor) in 108 individuals with Parkinson’s with Levodopa-induced dyskinesia (Click here to read more about this).
  • New clinical trial registered: NR-SAFE is a double-blinded randomized safety study aiming to determine the safety and tolerability of nicotinamide riboside at a daily dose of 3000mg for 4 weeks, in individuals with Parkinson’s (Click here to read more about this).
  • New clinical trial registered: Sage Therapeutics has initiated a study to evaluate the effects of SAGE-718 (NMDA receptor PAM) in 76 participants with Parkinson’s plus cognitive impairments (Click here to read more about this).

Clinical trial news

  • The results of the APOMORPHEE study – a multi-centre, randomised, controlled, double-blind crossover trial assessing safety & efficacy of subcutaneous night-time only apomorphine infusion to treat insomnia in patients with Parkinson’s – has been published (Click here to read more about this).
  • Aspen Neuroscience announces that it will launch this month the first patient screening study for a planned clinical trial of personalized cell replacement in Parkinson’s; This is for their Phase 1/2A clinical trial of ANPD001 (Click here to read more about this).

  • Results from the 1st-in-human clinical studies of UB-312 (an alpha synuclein targeting vaccine being developed by Vaxxinity for Parkinson’s & associated conditions) have been published; “Generally safe, well tolerated, & induced anti-α-Syn antibodies” (Click here to read more about this).
  • The safety & pharmacokinetics of multiple dosing with inhalable apomorphine (AZ-009) & its efficacy in a randomized crossover study in Parkinson’s has been published (Click here to read more about this).
  • Positive news for Inbrain Pharma with their pilot clinical study of A-dopamine in Parkinson’s. The company is exploring a method of direct delivery of dopamine to the brain (Click here to read more about this).

  • Long-term safety data from the Phase 2b BeyoND study of ND0612 (continuous, subcutaneous levodopa/carbidopa delivery system) demonstrates a positive safety & tolerability profile beyond one year in people with Parkinson’s (Click here to read more about this).
  • Neuraly have announced the completion of patient enrollment in its Phase 2 study of NLY01 – a GLP-1R agonist being developed for Parkinson’s; The study has enrolled 255 patients across 60 clinical sites in the US & Canada; Top-line results in H1 2023 (Click here to read more about this).

 

Conferences/lectures

  • 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).

Other news

  • PolyCore Therapeutics announces the securing of seed funding to help advance their lead compound, PCT-3012 (a novel G protein-biased D3 receptor agonist) to reduce motor impairment & dyskinesias in Parkinson’s (Click here to read more about this).
  • Neuropore Therapies announced today that it has received a $4.8M grant from
    the Michael J Fox foundation to support the preclinical & clinical development a of a novel brain-penetrating small molecule Toll-Like receptor 2 (TLR2) antagonist for Parkinson’s (Click here to read more about this).

  • German Pharma Bayer is investing a further €1.3B into its “Leaps by Bayer” investment arm to drive new therapies to the clinic for conditions like Parkinson’s (Click here to read more about this).
  • Shake it up Australia founder Clyde Campbell is asking 10,000 Aussies living with Parkinson’s to get involved in the Australian Parkinson’s Genetic Study to help advance research:
  • The US Centres for Medicare and Medicaid Services (CMS) has affirmed its draft decision to limit reimbursement of Biogen’s Alzheimer’s therapy Aduhelm/aducanumab to a few thousand patients enrolled in clinical trials; “The agency is prepared to provide “broad access” via Medicare “if a drug in this class shows evidence of clinical benefit through the traditional FDA approval process”” (Click here to read more about this).
  • Biogen has notified the EMA that it will withdraw its Marketing Authorization Application for aducanumab for the treatment of the early stages of Alzheimer’s, based on CHMP decision that the data provided thus far would not support authorization (Click here to read more about this).
  • On the cusp of Phase 2 testing, Abbvie has backed out of its collaboration with Bioarctic to develop alpha-synuclein-based immunotherapies for Parkinson’s (Click here to read more about this).

Review articles/videos

  • A useful review on the inhibition of colony stimulating factor-1 receptor (CSF-1R) as a potential therapeutic strategy for neurodegenerative diseases, explores the opportunities & challenges (includes a section on Parkinson’s – click hereto read more about this).
  • A new review discussing GBA genetic variants in Parkinson’s, exploring their mechanisms and possible treatments (Click here to read more about this).
  • An interesting editorial on Parkinson’s-associated LRRK2 – “Fifteen years from cloning to the clinic” – with links to a wealth of reviews (Click here to read more about this).

  • Time to consider n-of-1: “We propose that diagnosis should shift away from the clinical definitions, towards biologically defined diseases that collectively form Parkinson’s, to enable informative patient stratification” (Click here to read more about this).
  • A useful overview of current evidence for mitochondrial respiratory chain dysfunction as a pathological hallmark of idiopathic Parkinson’s; They highlight knowledge gaps & propose potential strategies for future research (Click here to read more about this).
  • Proteins do not replicate, they precipitate; And the associated loss of function, causes things to degenerate – interesting review (Click here to read more about this).
  • A new review explores sphingolipids pathway in Parkinson’s (Click here to read more about this).
  • The potential molecular & cellular pathways that may leave dopaminergic neurons susceptible, both directly & indirectly, to SARS-CoV-2 infection; Could COVID be an enhancer of Parkinson’s? (Click here to read more about this).

  • The midbrain & the enteric dopaminergic neurons originate & develop from different locations, but both are associated with Parkinson’s – now a new review explores the similarities & differences in these two populations (Click here to read more about this).
  • New commentary explores the challenges of incorporating digital health technology outcomes in a clinical trial – with insights from the PD-STAT clinical trial (Click here to read more about this).
  • New review highlights potential treatments which may act to target GCase & prevent neurodegeneration in GBA-associated Parkinson’s (Click here to read more about this).
  • Researchers outline a set of considerations informing a patient-centred approach to trial recruitment, retention, & delivery – a lot to digest here, loads of interesting insights! (Click here to read more about this).

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

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You can do whatever you like with it!


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.


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