# # # # 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 March 2022. The post is divided into 10 parts based on the type of research: Top 5 pieces of Parkinson’s news Articles of general interest Basic biology Disease mechanism Clinical research New clinical trials Clinical trial news Conferences/lectures Other news Review articles/videos # # # #

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So, what happened during March 2022?

In world news:

March 1st – It was announced that the US Patent and Trademark Office ruled that the Broad Institute of MIT and Harvard will retain their intellectual property over the use of CRISPR-Cas9 gene editing in eukaryotes – invalidating filings by the University of California, the University of Vienna, and Emmanuel Charpentier on use in eukaryotes.

 

March 6th – As the world watched the disaster unravelling in Ukraine, the UK Government quietly dropped plans to double their ‘moon shot’ dementia research fund, cutting the amount from £160 million to £75 million instead (Source). Probably due to the fraud and “error” on COVID-19 spending (possibly as much as £16 billion – Source). Well, at least no money was wasted on dodgy personal protective equipment (Source… I’m really no good at sarcasm).

 

March 16th – A cross-party report from the UK Government’s Digital, Culture, Media and Sport Committee criticised the “UNBOXED: Creativity in the UK” event (also known as the “Festival of Brexit”) as “vague and shape-shifting“, saying that it lacked clear direction and was an “irresponsible use of public money“. Taking place between March and November, the event will cost £120 million (Source).

 

March 30th – “I give you the light of Eärendil, our most beloved star” – Using gravitational lensing, NASA’s Hubble Space Telescope scientists detected light from the farthest individual star ever seen to date. They named it Eärendil. The newly detected star is so far away that its light has taken 12.9 billion years to reach Earth (Click here to read more about this).

March 31st – The Russian Ruble returned to pre-Ukraine invasion levels demonstrating the amazingly power and effectiveness of Western “sanctions”…

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

In March 2022, there were 1098 research articles added to the Pubmed website with the tag word “Parkinson’s” attached (3412 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. The NADPARK study results:

Norwegian researchers present the results of the NADPARK study: A randomized phase I trial of nicotinamide riboside supplementation in Parkinson’s; This was a small pilot (n=30) to the current NOPARK study; Oral nicotinamide riboside (1,000mg/day for 30 days) treatment was well tolerated & led to significant (but variable) increase in cerebral NAD levels (measured by MRS & CFS); NR also decreased levels of inflammatory cytokines in serum & CSF; Now in Phase II NOPARK trial (NCT03568968 – click here to read more about this, click here to read the press release associated with this study, and click here to read a SoPD post on this topic).

 

2. The silver linings of Parkinson’s:

Researchers share the results (& interpretations) of an online exploratory survey asking if there are any “silver linings to having Parkinson’s” – tough question, powerful piece! (Click here to read more about this and click here to read a SoPD post about this report).

 

3. A difference in identity?:

A new research paper reported “a glutamatergic identity in dopamine neurons may be part of a neuroprotective response in Parkinson’s”. The researchers found that the glutamatergic-associated protein, VGLUT2, can be increased in some dopamine neurons in response to injury, and this appears to protect those cells. They also reported that analysis of postmortem PD brains supported this idea (Click here to read more about this).

4. Time to replace your microglia?:

Something wrong with your microglia? Replace them! A new research paper reported that CNS-wide microglia replacement (using circulation-derived myeloid cells) slows neurodegeneration, corrects motor issues, & extends survival in transgenic mice (Click here to read more about this).

5. The impact of TLRs on LRRK2:

Australian researchers reported that monocytes & macrophages carrying the Parkinson’s-associated LRRK2 G2019S genetic variant had significantly increased levels of cytokines & chemokines in cell culture media following stimulation with TLR agonists compared to control cells. LRRK2 kinase inhibitors (a class of drug being developed for Parkinson’s) had little effect on TLR-mediated inflammation under these conditions. The “results suggest that the LRRK2 G2019S mutation may potentiate inflammation following activation of TLRs” (Click here to read more about this).

Articles of general interest

• “Experts offer advice on newer Parkinson’s medications, cautions, recommendations, & the big picture” (Click here to read more about this).
• Looking forward to following Guy Deacon on his 6,000 miles across Africa – from Freetown to Cape Town – to raise vital awareness for Parkinson’s (Click here to read more about this).

• Interesting discussion on how PhD programs embraced hybrid working situations during the COVID19 pandemic – 5 doctoral candidates share lessons they learnt (Click here to read more about this).
• New mini review on the disease modification conundrum in Parkinson’s: Failures & hopes – covers:  Timing woes, the unnatural nature of “pure & simple” preclinical designs, the age of target discovery, and the importance of the “Right” endpoints (Click here to read more about this).
• Interesting read from Phil Robinson – Chair of the development board at Cure Parkinson’s – it’s an update blog on his journey with Parkinson’ s (Click here to read more about this).

Basic biology news

• Metabolomics & biochemical alterations are reported in Parkinson’s model (6-OHDA) involving transgenic mice overexpressing the cytokine pleiotrophin; Interesting lipid-related PD drug candidates emerge (Click here to read more about this).
• Using an evolutionary approach, researchers find GATD3A acts as a resident mitochondrial deglycase removing non-enzymatic chemical modifications formed between amino groups of biomolecules & dicarbonyl byproducts produced from glucose & lipid oxidation; GATD3A displays a unique phyletic profile widely distributed across eukaryotes & bacteria; It is ubiquitous expression in humans, & displays significant homology with the Parkinson’s-associated protein DJ-1/PARK7 (Click here to read more about this).
• Could Parkinson’s patients exhibiting α-syn-specific T cell responses be associated with an inflammatory stage of the condition? New research compares the transcriptional profiles of peripheral T cells from individuals with/without PD (Click here to read more about this).

• New research presents a method of using isotope-labeled D3-leucine to measure protein turnover in human iPS cell organoids (via Mass Spec); “Robust computational method to determine protein half-lives” (Click here to read more about this).
• On the α-synuclein binding activity of the plant growth promoter asterubine (shares distinct structural similarities with B-amyloid aggregation inhibitors tramiprosate (homotaurine) & ALZ-801 – click here to read more about this).
• New research reports that phosphorylation of α-synuclein at residue serine 129 may occur subsequent to initial α-syn aggregation, lessening aggregation propensity, & attenuating cytotoxicity across diverse assays (Click here to read more about this).
• Drp1 is a master regulator driving mitochondrial fission. Now researchers have discovered that Clueless/CLUH is a key regulators of Drp1, by promoting its recruitment to the mitochondria; CLUH overexpression rescues Parkinson’s fly models (PINK & Parkin – click here to read more about this and click here to read a press release associated with this research).
• New research reports Parkinson’s & multiple system atrophy (MSA) patient iPSC-derived oligodendrocytes exhibit alpha-synuclein–induced changes in maturation & immune reactive properties (Click here to read more about this).

• New research reports Parkinson’s-associated α-synuclein is differently glycated by distinct glycating agents; Glycation primarily inhibits elongation rather than nucleation of α-syn (Click here to read more about this).
• New biorxiv manuscript finds that the Parkinson’s-associated A53E fibril is composed of a symmetrical fibril, & the interaction interface between wild-type alpha synuclein & A53E is different – changing the aggregation mechanism of α-syn (Click here to read more about this).
• Researchers report that LRRK2 inhibition mitigates the neuroinflammation caused by TLR2-specific α-synuclein & alleviates neuroinflammation-derived dopaminergic neuronal loss; LRRK2 phosphorylation was increased in Parkinson’s cases showing an αSyn-specific increase in TLR2 (Click here to read more about this).
• More evidence of SARS-CoV-2 proteins interacting with Parkinson’s-associated alpha synuclein (Click here to read more about this).
• Single molecule spectroscopy (“fingerprinting”) reveals different amplification properties of Parkinson’s-associated α-synuclein oligomers & preformed fibrils in seeding assay; “Oligomers were found to be seeding-competent, but our results reveal that their seeding behavior is very different compared to that of preformed fibrils, in our amplification assay… a low number of preformed fibrils present in biosamples is likely to dominate the response” (Click here to read more about this).

• Maintenance of mitochondrial integrity in dopamine neurons is governed by the conserved developmental transcription factor Fer2 (in flies); Homolog Nato3 cKO in mouse DA neurons = age-dependent locomotor/coordination issues (Click here to read more about this).
• New research integrates deep learning & unbiased automated high-content screening to identify complex disease signatures in human fibroblasts; They confidently separate LRRK2 & sporadic Parkinson’s lines from controls (Click here to read more about this).
• New biorxiv manuscript suggests that premature MeCP2 expression disturbs the subtype specification of midbrain dopamine neurons (Click here to read more about this).
• Researchers report that the E3 ligase TRIM1 recruits Parkinson’s-associated LRRK2 to the microtubule cytoskeleton for ubiquitination & proteasomal degradation by binding LRRK2(911–919); TRIM1 rescues LRRK2 G2019S neurite outgrowth deficits (Click here to read more about this).
• New biorxiv manuscript underlines “the importance of a balanced healthy diet & its implications in disease progression“; Dietary fibre deprivation & bacterial curli exposure exacerbate Parkinson’s mouse model (Click here to read more about this).

• A small study, but researchers report evidence of picornavirus antigen in 7 of 9 Parkinson’s postmortem samples of midbrain, compared to only 1 of 11 control samples; Antigen was present in dopamine-containing neurons of the substantia nigra (Click here to read more about this).
• Dimethyl sulfoxide (DMSO) is a widely used reagent in research. Now researchers report low dose DMSO treatment induces oligomerization & accelerates aggregation of Parkinson’s-associated alpha synuclein (in vitro, but not in vivo – click here to read more about this).
• New study reveals that the presence of HEPES in the cell culture medium significantly impacts on cellular GCase – implications for studies exploring GBA-associated Parkinson’s? (Click here to read more about this).
• New research identify CaMKII as a pivot point between mitochondrial defects & axon degeneration; Cell-specific activation of CaMKII/UNC-43 suppresses axon degeneration due to loss of mitochondria (Click here to read more about this).
• New paper reports that replacement of Parkinson’s-associated mutant LRRK2 with wildtype LRRK2 in peripheral T- & B-cells reduces the peripheral inflammatory response to LPS; Anti-IL-6 prevents cell loss in LPS-treated mutant LRRK2 mice (Click here to read more about this).

• Researchers present a light-inducible protein aggregation (LIPA) system for in vivo analysis of α-synuclein aggregation in models of Parkinson’s; Interesting new tool – enables spatiotemporal control of α-syn aggregation in vitro; Plus: In vivo, LIPA-α-syn aggregates compromise nigrostriatal transmission, induce neurodegeneration & Parkinson’s-like motor impairments in wild-type mice (Click here to read more about this).
• New research proposes that Parkinson’s-associated α-synuclein has the potential to inhibit protein trafficking pathways that are dependent on phox-domain proteins (such as sorting nexins – click here to read more about this).
• New research reports “synergistic prion-α-synuclein interactions within condensates provide mechanistic underpinnings of their physiological role and overlapping neuropathological features”; N-terminal segment of prion & C-terminal tail of α-synuclein (Click here to read more about this).
• New biorxiv manuscript continues the astrocyte-to-neuron conversion saga: 2 AAV-based tracing systems gives conflicting results; “data showing in vivo neuronal lineage conversion obtained by reporter proteins…should be taken with caution” (Click here to read more about this).
• New biorxiv manuscript provides further single cell transcriptomic analysis of the human Substantia Nigra in Parkinson’s; Highlights the heterogeneity of the dopamine neurons & suggests possible molecular basis for vulnerability & resilience (Click here to read more about this).

• A blow-by-blow unraveling of the sequence of synaptic functional & structural changes preceding dopaminergic cell death in a rodent model of Parkinson’s (overexpression of human mutated A53 T α-synuclein in the nigra) identifies some key proteins involved (Click here to read more about this).
• New biorxiv manuscript “provides a structural rationale for fibril-induced lipid extraction, a mechanism likely to be involved in the development of α-synucleinopathies”; Phospholipids favor a novel protofilament fold (Click here to read more about this).
• An analysis of gender differences in mice treated with the O-GlcNAcase enzyme inhibitor Thiamet G reveals sex-dependent nodes responsive to acute increases in O-GlcNAc levels; Alterations to networks associated with bioenergetics, autophagy, & neurodegeneration (Click here to read more about this).
• New biorxiv manuscript suggests that monomeric α-Synuclein can colocalize with the plasma membrane Ca 2+-ATPase & activate calcium expulsion (Click here to read more about this).
• Microglias making themselves at home in organoids – Microglia integration into human midbrain organoids leads to increased neuronal maturation & functionality (Click here to read more about this).

• New research reports that α-synuclein species from multiple system atrophy-derived glial cytoplasmic inclusions can induce a pathological process in non-human primates (a 2-year in vivo phase – click here to read more about this).
• Long-term hyperglycemia (induced by streptozotocin) aggravates α-synuclein aggregation & dopaminergic neuronal loss (plus neuroinflam.) in a Parkinson’s mouse model; A PD model incorporating diabetes (Click here to read more about this).

Disease mechanism

• Kainos Medicine-associated researchers present data indicating the pharmacological intervention targeting Fas-associated factor 1 (FAF1; with inhibitor KM-819) restores autophagic flux for α-synuclein degradation in the brain of a Parkinson’s mouse model (Click here to read more about this).
• Niacin (nicotinic acid) receptor HCAR2 inactivation in Alzheimer’s mice (5xFAD) exacerbates cognitive impairments & amyloid-β burden, whereas HCAR2 activation using the FDA-approved drug Niaspan had protective effect & rescued working memory deficits (Click here to read more about this).

• Boosting cathepsin D (in murine & human neurons) enhances Parkinson’s-associated α-synuclein degradation in models of α-Synucleinopathy; Also restores the number & size of SYN1-positive puncta (Click here to read more about this).
• Researchers report that an in-diet administration of the PARP inhibitor ABT-888/Veliparib demonstrated outstanding brain penetration, but had limited impact on an alpha synuclein mouse model of Parkinson’s (Click here to read more about this).
• Like characters from a Marvel movie: SuperDopa & SuperDopamide – researchers present 2 dopamine precursors, AcCys-L-Dopa-Cys-amide (SuperDopa) & N-acetylcysteine+DopAmide (SuperDopAmide), as potential neuroprotective agents for slowing Parkinson’s (Click here to read more about this).
• Researchers in Nigeria report resveratrol alleviated oxidative stress & locomotor deficit in a Parkin loss-of-function drosophila (fly) model of Parkinson’s (Click here to read more about this).

• New research finds a type II positive allosteric modulator of α7 nAChR called PNU-120596 amends neuroinflammatory & motor issues in a 6-OHDA model of Parkinson’s (via JAK2/NF-κB/GSk3β/TNF-α pathway – click here to read more about this).
• New research reports a neuroprotective mechanism where sustained chemogenetic activation of locus coeruleus norepinephrine neurons preserves dopaminergic neurons in alpha synuclein-based model of Parkinson’s (Click here to read more about this).
• Researchers report that acidic nanoparticles can re-acidify lysosomes, increasing α-synuclein degradation via enhancing lysosomal activity (in vitro & in vivo) ameliorating α-synuclein pathology in mice (Click here to read more about this).
• New research demonstrated that new PACAP glycopeptide analogues (2LS80Mel & 2LS98Lac) were able to elicit neuroprotection in animal models of traumatic brain injury & a mild-lesion model of Parkinson’s (Click here to read more about this).
• Researchers present data demonstrating that CD200-CD200R1 signaling is altered in Parkinson’s; May affect microglial function & could constitute a potential target for therapeutic strategies (Click here to read more about this).
• New research presents a small molecule “C381” (from phenotypic CRISPRi screen) that targets the lysosome to reduce inflammation & ameliorate models of neurodegeneration, including Parkinson’s (Click here to read more about this).

• Takeda G protein-coupled receptor-5 (TGR5) agonist INT-777 alleviates inflammatory neurodegeneration in Parkinson’s mouse model by modulating mitochondrial dynamics in microglia; Inhibits the release of TNF-α from microglia (Click here to read more about this).
• Researchers in Thailand present a physicochemical investigation of a novel curcumin diethyl γ-aminobutyrate (CUR-2GE – a carbamate ester prodrug of curcumin) with enhanced anti-neuroinflammatory activity (Click here to read more about this).

Clinical research

• Fresh platelets from the blood of 75 individuals with Parkinson’s, 116 matched controls & 24 people with Parkinsonism exhibits a dramatic decrease in the serotonin content & uptake by secretory vesicles in PD cases; New biomarker? (Click here to read more about this).
• A study exploring the diagnostic value of salivary Real-Time Quaking-induced conversion in Parkinson’s & multiple systems atrophy (MSA) finds the lag phase of RT-QuIC assay from PD patients was significantly shorter than that of patients with MSA (Click here to read more about this).
• Exercise is good for people with Parkinson’s, but what can you do to encourage it? Maybe offering more group PD exercise classes will help? Read this study of exercise classes at Parkinson’s Foundation centres of excellence (Click here to read more about this).

• New medrxiv manuscript provides a proteogenomic view of the causality & heterogeneity of Parkinson’s; LRRK2 & GBA cohorts are investigated, & a hypothesis-free stratification revealed two patient endotypes for idiopathic PD; And GPNMB again! (Click here to read more about this).
• Distinct alterations in cerebellar connectivity with substantia nigra & ventral tegmental area in Parkinson’s (VTA-right cerebellum connectivity was higher than SN-right cerebellum connectivity, whereas the opposite trend occurred in controls – click here to read more about this).
• New research finds the incidence of Parkinson’s in the UK remained stable between 2006 & 2016 (accounting for age & diagnostic patterns), suggesting no major changes in underlying risk factors in the UK (Click here to read more about this).
• New medrxiv manuscript used neuromelanin-sensitive magnetic resonance imaging & found that the substantia nigra pars compacta volume & locus coeruleus volume were significantly reduced in individuals with Parkinson’s (both discovery & validation cohorts – click here to read more about this).
• Researchers report a retrospective cohort study that found an association between lithium use & the incidence of dementia & its subtypes; N=29,618 (548 exposed to lithium); Lithium use associated. with lower risk of dementia (HR 0.56 – click here to read more about this and click here to read a press release associated with this study).
• New study reports 82% of the patients with Parkinson’s, DLB or MSA had synuclein aggregates in the nerves innervating the heart. None of the controls exhibited such aggregates (Click here to read more about this).
• A nationwide study of the incidence, prevalence & mortality of Parkinson’s in the Norwegian population (2004–2017, 12,229 males & 9831 females identified as diagnosed with PD – click here to read more about this).

• No significant differences in gastrointestinal symptoms between symmetric & asymmetric dopaminergic defects (dopamine transporter asymmetry) in 90 early Parkinson’s cases (Click here to read more about this).
• A post-mortem study of 14 Parkinson’s cases (vs 12 matched controls) reports the PD group had increased α-syn in skin (5x control), submandibular gland (35x), & myocardial tissues (11x), but α-syn deposits in sympathetic nerves do not seem to be pathogenic (Click here to read more about this).
• “The identification of genetic lesions in lysosomal genes increasing Parkinson’s risk may have important implications in terms of patient stratification for future therapeutic trials” – on the burden of lysosomal gene variants in modulating GBA-PD risk (Click here to read more about this).
• On the relevance of brain hypometabolism – New research suggests that “in dementia with Lewy bodies, striatal dopaminergic depletion & brain hypometabolism are closely related, & they differentially affect cognitive dysfunction in an item-specific manner” (Click here to read more about this).
• The pathophysiology of Parkinson’s tremor – the researchers “show that PD tremor is associated with the synchronization of cerebral oscillations in 2 partially overlapping central networks”: cerebello-thalamo-CTX circuit & BG-CTX loop (Click here to read more about this).
• Mild-to-moderate Parkinson’s cases with normal muscle tone during rapid eye movement sleep have compensatory-like adaptations in white matter microstructure, but these are reduced or absent in RBD cases (Click here to read more about this).

• New study indicates that the hallucinating is associated with functional network segregation in Lewy body dementia & supports the involvement of the cholinergic system (Click here to read more about this).
• New retrospective cohort study using 2008–2019 healthcare data from Korea finds angiotensin II receptor blockers with CNS-penetrating properties & a high cumulative duration significantly reduces the risk of Parkinson’s in ischemic heart disease patients (Click here to read more about this).
• Researchers present “an easy-to-use, multivariable model that predicts the risk of dementia in Parkinson’s within 10 years with high accuracy (area under the curve: 0.86, P < 0.001)” (Click here to read more about this).
• New research suggests that early dopaminergic denervation in Parkinson’s follows a somatotopically related pattern: Starting with the upper-limb representation in the putamen & progressing over a 2-year period in the less-affected hemisphere (N=15 – click here to read more about this).
• New research evaluates the timing of physical therapy delivery in Parkinson’s; N=30; Burst (2x weekly for 6 weeks) vs spaced (1x every 2 weeks for 6 months); Spaced physical therapy = stability of timed up & go scores (Click here to read more about this).

• Researchers report a hidden layer of structural variation in transposable elements which could act as potential genetic modifiers in human disease-risk loci; They explore Parkinson’s-(LRRK2) & Alzheimer’s-associated genes (Click here to read more about this).
• New brain imaging research finds that stereotyped changes in adaptive & pathological connectivity patterns underlie disease progression & treatment responses in Parkinson’s brain networks (Click here to read more about this).
• New research presents a case-control study of 1055 individuals who developed Parkinson’s, noting the broad range of symptoms that people present in the primary care setting up to a decade before diagnosis (Click here to read more about this).
• Researchers report “an uncertain, increased risk of spinal muscular atrophy & dystonia” following electrical injury, but no increased risk of Parkinson’s, essential tremor, multiple sclerosis or other neurodegenerative conditions; (N=14,112; 19 years, 2 Danish registries – click here to read more about this).
• New research finds differential DaT-functional connectivity patterns observed among the genotypic groups in prodromal Parkinson’s (LRRK2 & GBA cohorts); Can DaTscan & FC assessments predict PD risk in these groups? (Click here to read more about this).
• New medrxiv manuscript finds plasma Melanoma Inhibitory Activity Protein, C-Reactive Protein, & albumin predict cognitive decline in Parkinson’s; Plasma-based predictor 4 risk of cognitive decline? (Click here to read more about this).
• Using 5-yr longitudinal data on  301 de-novo idiopathic Parkinson’s cases in the Michael J Fox foundation’s PPMI study, researchers report a link between measurable, baseline clinical symptoms in those without postural instability & development of postural instability (Click here to read more about this).

• Reduced risk of incident Alzheimer’s in 15,820 people with type 2 diabetes randomized to GLP-1R agonists in clinical trials and in Danish registry data (N=120,054 PPL – click here to read more about this).
• New research presents the first prospective study of prediagnostic features of Multiple System Atrophy (MSA); Issues like postural hypotension, urinary + bowel dysfunction, & early balance impairment are noted (Click here to read more about this).
• New research explores the cost effectiveness of levodopa/carbidopa intestinal gel compared to the standard of care for patients with advanced Parkinson’s in England, using real-world data (Click here to read more about this).
• Data from the HELIAD (Hellenic Longitudinal Investigation of Aging & Diet) study finds more pro-inflammatory diet is related with higher prodromal Parkinson’s probability & incidence (pPD probability ≥30%) in a community-dwelling older adult population (Click here to read more about this).
• Researchers find subcortical brain iron deposition is highly predictive of mitochondrial impairment in patients with idiopathic Parkinson’s in vivo (SWI & MRS imaging) – interconnectedness between 2 important patho-physiological hallmarks (Click here to read more about this).
• Useful thoughts on best practice approaches to outpatient management of people living with Parkinson’s during the COVID-19 pandemic – important implications going forward (Click here to read more about this).
• New study finds that adults on statins have a reduced risk of Parkinsonism that may be partially mediated by a lower odds of brain atherosclerosis – highlighting potential role of cerebrovascular pathologies in late-life parkinsonism (Click here to read more about this).

New clinical trials

• New clinical trial registered: Emerald Innovations is initiating a clinical study in LRRK2 genetic variant carriers – the Objective, Passive Assessment of LRRK2 Carriers (OPAL) study assessing early signs of Parkinson’s using wifi technology (Click here to read more about this).

• New clinical trial registered: The ‘AMBITIOUS study’ will be exploring 52 weeks ambroxol treatment as a potential disease-modifying treatment in 60 individuals with GBA-associated Parkinson’s; This Phase 2 study is being conducted in Milan & Pavia, Italy (Click here to read more about this).
• New clinical trial registered: Invicro has initiated a study to determine the safety & tolerability of an α-synuclein targeted radiopharmaceutical called [18F]UCB-2897 in participants with Parkinson’s &/or MSA relative to unaffected volunteers (Click here to read more about this).

• New clinical trial registered: “A study to see how BIIB122 works in the human body, & to evaluate it’s safety, & tolerability in healthy adult Japanese, Chinese, & caucasian participants (BIIB122 is the LRRK2 inhibitor DNL151, which is being developed for Parkinson’s – click here to read more about this).
• Interesting to note that Biogen & Denali Therapeutics also conducted another Phase I last year on BIIB122/DNL151 – now completed – in healthy individuals (Click here to read more about this).

Clinical trial news

• Digestome Therapeutics announces that the first patient has been enrolled in a Phase 1 clinical trial investigating DGX-001 – an oral, vagus nerve stimulating therapeutic targeting non-motor symptoms in patients with Parkinson’s (Click here to read more about this).
• Neuron23 closes $100M in series C, & announces NEU-723, a brain-penetrant LRRK2 inhibitor, will be entering clinical testing for Parkinson’s by end of 2022 (Click here to read more about this).

• The US FDA Peripheral & Central Nervous System Drugs Advisory Committee (PCNSDAC) voted 4 (yes) & 6 (no) on a pending NDA for Amylyx Pharma‘s AMX0035 (sodium phenylbutyrate & taurursodiol) for ALS; Remember: recommendations by the panel are non-binding (Click here to read more about this).
• Anavex Life Science presents Phase 2 clinical biomarker data from the ANAVEX®2-73-PDD-001 Parkinson’s disease dementia study at the 2022ADPD meeting (Only the high dose data is presented? – click here to read more about this).
• Sage Therapeutics presented results from their Phase 2 open-label PARADIGM Study (Part A) of SAGE-718 (NMDA receptor PAM modulator) in individuals with mild cognitive impairment due to Parkinson’s (Click here to read more about this).

• The results of the ALLAY-LID studies have been published: Immediate-release/extended-release amantadine significantly reduced Parkinson’s-associated levodopa induced dyskinesia in ALLAY-LID II but not in ALLAY-LID I (Click here to read more about this).
• At the 2022ADPD meeting, AC Immune presents their first live images of alpha-synuclein in the human brain with a new PET tracer (ACI-12589) being developed for neurodegenerative conditions like Parkinson’s & MSA (Click here to read more about this). “The ACI-12589 patient brain scans indicate the signal specificity for a-syn in MSA patients versus healthy volunteers & patients with other a-synucleinopathies” (Click here to read more about this).
• Annovis Bio are presenting an update on the study designs of their upcoming Phase 3 trials evaluating Buntanetap (ANVS401/Posiphen) in Parkinson’s at the 2022ADPD meeting; In January, the US FDA gave guidance on 2 Phase 3 trials in early & late PD (Click here to read more about this).

• Managing fatigue in Parkinson’s; The protocol for a pilot randomized controlled trial assessing the feasibility of the “Managing Fatigue: Individual Program” (MFIP) delivered via videoconference will be assessed (Click here to read more about this).
• Prothena presents new preclinical data at the 2022ADPD meeting on their dual Aβ/tau vaccine being developed for Alzheimer’s & their tandem C-terminal α-synuclein vaccine for Parkinson’s; Also more data from their Phase 2 PASADENA study (Click here to read more about this).
• “Much of the positive data on the effect of prasinezumab on motor signs in Parkinson’s was captured using a novel digital health technology” – interesting summary of data presented at the 2022ADPD meeting by Roche & Prothena (Click here to read more about this).

• A new study provides Class II evidence that sustained increase in overall regular physical activity levels in patients with early Parkinson’s was associated with slower decline of several clinical parameters (Click here to read more about this).
• The rationale & design of the Phase IV randomised, double-blind OCEAN (OpiCapone Effect on motor fluctuations & pAiN) trial in Parkinson’s has been published (Click here to read more about this).
• Cortexyme presented new data from their Phase II/III GAIN trial of atuzaginstat in mild/moderate Alzheimer’s at the 2022ADPD meeting, showing the drug inhibited lysine gingipains, plus 30%-50% reduction in cognitive decline in high P. gigivalis load cases (Click here to read more about this).

• A pooled analysis of 2 Phase III Gocovri (amantadine-delayed release/extended release capsules) trials (NCT02136914, NCT02274766) followed by a 2-year open-label extension trial (NCT02202551) demonstrates significantly reduce OFF time in Parkinson’s (Click here to read more about this).
• The Phase 3 results of the first drug claimed to be disease-modifying in Alzheimer’s to be published in Journal of Prevention of AD (Full disclosure: JPAD’s editor-in-chief Dr Paul Aisen is one of the lead investigators on the Aduhelm (aducanumab) studies – click here to read more about this).
• In addition, Biogen has presented new data at the 2022ADPD meeting indicating that data from both Phase 3 studies show that clinical decline was reduced in participants who had plasma p-tau181 reduction at 78 weeks; Also: “In the placebo-controlled period of the Phase 3 trials, the incidence of ARIA-E in the 10 mg/kg group was 35.2%. The incidence was higher among APOE ε4 carriers (43.0%) than non-carriers (20.3%)” (Click here to read more about this).

Conferences/lectures

• Cure Parkinson’s is holding their annual research update meeting on Wednesday 4th May between 14:00 – 18:30 (Click here to read more about this).
  
• 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

• Vyant Bio & Organo Therapeutics announced a collaborative agreement to work towards accelerating the discovery of drugs for the treatment of Parkinson’s (Click here to read more about this).
• Gain Therapeutics presented data on their orally bioavailable, brain-penetrant lead drug candidates for Alzheimer’s & GBA-associated Parkinson’s at the 2022ADPD meeting (Click here to read more about this).

• Nitrase Therapeutics (formerly Nitrome Biosciences) presents new data at the 2022ADPD meeting on the discovery of nitrated alpha synuclein species as robust cerebrospinal fluid-based biomarkers for Parkinson’s (Click here to read more about this).
• SQZ Biotechnologies announces a $2 million grant from the NIH for “Directly creating dopamine-producing neurons by reprogramming a patient’s own immune cells” for the treatment of Parkinson’s (Click here to read more about this).
• Under-represented communities: What does Parkinson’s look like for Māori & Pacific islanders living in Aotearoa? Michael J Fox Foundation has awarded a grant to investigate. Ka pai! (Click here to read more about this).

Review articles/videos

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

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You can do whatever you like with it!

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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.

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