# # # # 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 October 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 October 2022?

In world news:

6th October – An open source platform (called “MatchMiner“) which matches genomically profiled cancer patients to precision medicine drug trials is presented (Click here and here to read more about this).

 

7th October –  Neuroscientists report experimental MRI results suggesting that brain functions operate non-classically and their data may support the idea of quantum mechanisms being involved in consciousness as the signal pattern declined when human participants fell asleep (Click here to read more about this).

 

16th-23rd October – The 20th National Congress of the Chinese Communist Party is held. Xi Jinping is elected as General Secretary of the Chinese Communist Party by the Central Committee, beginning a third term as the leader of China.

 

20th October – UK Prime Minister Liz Truss resigned after 45 days in the role.

 

28th October – Elon Musk completed his $44 billion acquisition of Twitter.

 

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

In October 2022, there were 902 research articles added to the Pubmed website with the tag word “Parkinson’s” attached (9786 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. New cell transplantation study launched:

Swedish authorities have granted approval for a clinical trial of stem cell-derived cell transplantation therapy for the treatment of Parkinson’s. The trial – called STEM-PD – will involve recruiting a total of 8 patients for transplantation, starting with participants in Sweden, and with subsequent plans for enrolment of patients in Cambridge, UK (Click here to read more about this).

 

2. Mitochondria. Always mitochondria:

Researchers in Sweden reported that Parkinson’s is associated with a 20% lower number of mitochondrial DNA copies, but 26% longer telomeres (in blood vs controls). Telomere length in blood positively correlated with medication (L-dopa) & disease duration. In the brain, Parkinson’s, PD dementia & Dementia with Lewy Bodies case “showed (46–95%) depleted mtDNA copies, but (7–9%) longer telomeres” vs controls. Plus, lower mitochondrial biogenesis (PGC-1α & PGC-1β) & higher load of a cellular senescence marker in postmortem CNS tissue (Click here to read more about this).

 

3. Neflamapimod presents encouraging results:

Preclinical & randomized clinical evaluation (NCT04001517) of the p38α kinase inhibitor neflamapimod in mild-to-moderate dementia with Lewy bodies presented encouraging results. Preclinical testing of agent protected neurons in a model of basal forebrain cholinergic degeneration. And then in a clinical pilot study (N=91, 16-weeks of treatment, double-blind study), neflamapimod did not show an effect on the primary endpoint (a cognitive-test battery), but on secondary endpoints (a measure of functional mobility & a dementia rating-scale) improvements were observed (Click here to read more about this).

 

4.  When the data says the opposite to what you might expect

Researchers reported that high cerebrospinal fluid Aβ42 levels predict normal cognition in amyloid-positive individuals with Alzheimer’s-causing genetic mutations; The study involved 232 mutation carriers (Click here to read more about this and click here to read a press summary about this research).

5.  Multiple papers providing insights into GCase-associated activity 

Lower cerebrospinal GCase activity at time of diagnosis may predict outcomes. GCase activity was lower in Parkinson’s patients who developed dementia within 10 years than in those who did not (p = 0.001). A 0.1 unit reduction in baseline GCase activity was associated with a faster development of PDD (Click here to read more about this). And in a second paper, researcher’s reported lysosomal lipid alterations caused by glucocerebrosidase deficiency can promote lysosomal dysfunction, chaperone-mediated-autophagy deficiency, & alpha-synuclein pathology (Click here to read more about this).

 

Articles of general interest

• A special open access issue of Journal of Parkinson’s is dedicated to the involvement of the immune system in Parkinson’s (Click here to read more about this).
• “What type of exercise is best for people with Parkinson’s” by Prof Bas Bloem:

• I recently had the pleasure of meeting Prof Mark Mattson, & he told me about his podcast “Brain ponderings” that he started this year. I have been listening to some of the Parkinson’s episodes this weekend, & have been really impressed:

• Prof Frank Church’s has a good post on exercise on his blog (Click here to read more about this).
• As part of its 30th-anniversary celebrations, Parkinson’s Europe has launched a new manifesto outlining 30 wishes from the community (Click here to read more about this and click here to read the new manifesto)
• Pesticide and Parkinson’s – journalists at the Guardian newspaper explore this topic (Click here to read more about this).

 

Basic biology news

• New research indicates that the quaternary structure of patient-homogenate amplified α-synuclein fibrils modulates seeding of endogenous α-synuclein inside recipient cells (Click here to read more about this).
• New research reports EGCG has dual & opposing effects on the N-terminal region of self-associating α-synuclein oligomers; Both effects decrease membrane permeabilization, thereby detoxifying the oligomers (Click here to read more about this).
• Researchers report that Parkinson’s-associated Parkin drives pS65-Ub turnover independently of canonical autophagy (in drosophila) – Pink1-Parkin pathway can promote mitochondrial turnover independently of canonical autophagy in vivo (Click here to read more about this).
• Further efforts in the development of an α-synuclein fibril & oligomer specific tracer for diagnosis of Parkinson’s, dementia with Lewy bodies & multiple system atrophy (MSA – Click here to read more about this).

• New research explores the effects of mutations & post-translational modifications on the in vitro aggregation of Parkinson’s-associated α-synuclein (Click here to read more about this).
• New research reports that the ADORA1 mutation linked to early-onset Parkinson’s alters adenosine A1-A2A receptor heteromer formation & function (Click here to read more about this).
• Researchers report that primary pericytes take up aggregated Parkinson’s-associated α-synuclein; It does not induce an inflammatory response, but renders these cells vulnerable to apoptosis under cellular stress (Click here to read more about this).
• Researchers report on the mechanism of by which 4-aminopyridine – a broad potassium channel inhibitor – modulates the Parkinson’s-associated lysosomal channel TMEM175; It binds in the ion conduction pathway of TMEM175, preventing water & ions from crossing (Click here to read more about this).
• The absence of Parkinson’s-associated Parkin does not promote dopamine or mitochondrial dysfunction in PolgAD257A/D257A mitochondrial mutator mice (Click here to read more about this).
• New research used CRISPR-Cas9 to make incremental number of SNCA genes in SNCA triplication iPSCs & treated them with seeded α-Syn aggregation to provide a cellular platform to investigate mechanisms of Parkinson’s (Click here to read more about this).
• Dopaminergic neurons do NOT express sonic hedgehog in the adult mouse brain; Nor is dopamine neuron-derived SHH ligand critical for striatal cholinergic or fast spiking GABAergic neuron survival; GDNF levels are not changed in DATcre-shh cKO mice (Click here to read more about this).

• Researchers demonstrate that plasma membrane Cav1 Ca2+ channels trigger an intracellular Ca2+ signaling cascade that engages endoplasmic reticulum ryanodine receptors to stimulate mitochondrial ATP synthesis to help meet the bioenergetic demand. “In building out the mechanistic connection between Cav1 channels, mitochondria, & Parkinson’s risk, our studies have identified other potential disease-modifying targets” (Click here to read more about this).
• Researchers report SIAH3 (a SIAH protein but lacking ubiquitin-ligase activity) is increased in Parkinson’s brains, CSF & neurons treated with α-synuclein preformed fibrils; It also aggregates with PINK1 in the mitochondria of PD brains, triggering a toxicity cascade of PINK1 inactivation. They also report SIAH1 interacts with PINK1 & promotes its ubiquitination & proteasomal degradation; SIAH3 inhibits this activity & promotes the translocation of SIAH1 to mitochondria; Does intra-mitochondrial aggregates represent a novel aspect of Parkinson’s pathogenesis? (Click here to read more about this).
• I grew up around Ginkgos & now researchers are exploring the properties in the context of Parkinson’s. Funny how things come full circle… (Click here to read more about this).
• New biorxiv manuscript “sheds light on differences between interactions of alpha synuclein with synthetic lipid vesicles & physiological synaptic vesicles”; Parkinson’s-associated a-synuc. fibrils may disintegrate SVs (Click here to read more about this).
• New research used solid imaging & modeling approaches to explain “how axonal microtubules orient uniformly, a prerequisite for efficient long-range transport essential for neuronal functioning” (Click here to read more about this).

• Using primary mouse cells, researchers find that certain types of neurons (that are differential more vulnerable in Parkinson’s) are endowed with larger axonal domains, which are more complex & have more axonal varicosities (Click here to read more about this).
• New research finds that deficiency of the frontotemporal dementia gene GRN results in lysosomal ganglioside accumulation; Granulins are needed to maintain BMP levels to support ganglioside catabolism (Click here to read more about this).
• New biorxiv manuscript provides a novel function of octopamine as a modulator of astrocyte metabolism (via a TAAR1-Orai1-Ca2+-calcineurin-mediated signaling) & subsequent neuroprotection; Implications for Parkinson’s? (Click here to read more about this).
• Researchers report that cathepsin L-containing exosomes from α-synuclein-activated microglia induce neurotoxicity through the P2X7 receptor; P2X7R knockdown & exosome release inhibitors significantly reduced the injury to cultured mouse cortical neurons (Click here to read more about this).
• You know how oligodendrocytes have become a thing in Parkinson’s with all of the single cell sequencing work on post mortem tissue? New research finds inactivation of macroautophagy in oligodendrocytes leads to behavioral dysfunction & neurodegeneration in mice (Click here to read more about this).
• Aggregation-seeding forms of Parkinson’s-associated α-synuclein are not detected in acute COVID-19 cerebrospinal fluid (Click here to read more about this).
• New paper explores α-synuclein aggregation properties in the presence of DMPS lipid vesicles for wild-type α-synuclein & five of the most predominant single point missense mutants associated with early onset Parkinson’s (Click here to read more about this).
• An examination of the brain lipidome of mice across lifespan using untargeted lipidomics highlights a class (3-sulfogalactosyl diacylglycerols) of anti-inflammatory lipids that progressively decrease with aging; Detection of SGDGs in human & macaque brains (Click here to read more about this).

• New paper presents quantitative super-resolution imaging & analysis of alpha synuclein aggregates from Parkinson’s & dementia with Lewy bodies cases, revealing distinct toxicity profiles (Click here to read more about this).
• New biorxiv manuscript presents ~1.5M single-cell transcriptomes & ~400K single-cell chromatin accessibility profiles across mouse brains spanning different ages, genotypes, & both sexes. And then, just for kicks, the researchers profiled 118,240 single-nuclei transcriptomes from 24 human brain samples derived from control & Alzheimer’s patients, revealing highly cell-type-specific & region-specific gene expression changes associated with AD pathogenesis (Click here to read more about this).
• New research reports that dopamine D2 receptor signaling in striatal spiny neurons modulates L-DOPA-induced dyskinesia (in mice – click here to read more about this).
• Some of the best in the business discuss the “SynFib” model (a combo. of pre-formed α-synuclein fibrils & overexpression of α-synuclein using AAV vectors) of Parkinson’s, summarizing the experience gained so far & key parameters (Click here to read more about this).

Disease mechanism

• New biorxiv manuscript presents a high content imaging-based screen of 940K small molecules to identify those that accelerate lipid droplet clearance; Highlights EIF2AK3/PERK activator CCT020312 as a mTOR inhibitor-independent autophagy activator (Click here to read more about this).
• New research finds that targeted deletion of SYK in microglia leads to exacerbated Aβ deposition, aggravated neuropathology, & cognitive defects in Alzheimer’s mice (5xFAD); Activation of SYK limits Aβ load (Click here to read more about this).

• The aggregation of aminoacyl transfer RNA synthetase complex-interacting multifunctional protein-2 (AIMP2) accelerates Parkinson’s-associated α-synuclein. Now researchers present inhibitors of AIMP2 that block α-synuclein aggregation in vitro (Click here to read more about this).
• Transcriptomic data of midbrain neurons reprogrammed from Parkinson’s patients & controls highlights druggable pathways (Lanoteplase?!?); Implicates synaptic dysfunction in PD patho. driven by genetic predispositions (Click here to read more about this).
• Researchers use transcriptome-wide association study (TWAS) to find 160 candidate genes whose misexpression is associated with Parkinson’s risk, & then hi-thru.put analyses in drosophila to discover that 50 candidates can modulate α-Syn-associated neurodegeneration (Click here to read more about this and click here to read the press summary).
• STX is a selective estrogen receptor modulator; New research reports that oral STX treatment attenuated Aβ-associated mitochondrial toxicity & synaptic toxicity in an Alzheimer’s model (5XFAD mice); Also improved improved spatial memory (Click here to read more about this).
• Researchers present lentiviral-based NLRP3 knockdown in a MPTP model of Parkinson’s (in vitro & vivo); Inhibition of the inflammasome in the substantia nigra significantly reduces dopamine neuronal loss & microglia activation (Click here to read more about this).

• A new biorxiv manuscript presents a potential molecular mechanism by which pathologic α-synuclein activates mTORC1 leading to enhanced protein translation & concomitant neurodegeneration in Parkinson’s (flies & mice data); Human PD nigra= reduced TSC1-TSC2 levels (Click here to read more about this).
• A new biorxiv manuscript presents a drug screening experiment that identifies clinically available compounds that inhibit Parkinson’s-associated α-synuclein oligomers’ membrane disruption; “useful in guiding future therapeutic strategies” (Click here to read more about this).

Clinical research

• New research presents a retrospective study, involving longitudinal analysis of axial impairment & falls in Parkinson’s with subthalamic nucleus deep brain stimulation, from baseline to 15 years post surgery (Click here to read more about this).
• New research finds that the functional connectivity pattern of the sensorimotor cortico-striato-thalamic-cortical loop is influenced by nigrostriatal innervation in Parkinson’s (N includes 39 PD & 16 essential tremor – click here to read more about this).
• NCER-PD Consortium researchers identify an RBD-specific Parkinson’s endophenotype, characterized by predominant autonomic dysfunction, hallucinations, & depression, corroborating the concept of a distinctive body-first subtype of PD (Click here to read more about this).

• Is it just me, or do DBS papers have the best figures? They certainly help with “understanding the functional architecture of the human basal ganglia & provide mechanistic explanations of non-motor symptoms in brain circuit disorders” (Click here to read more about this).
• A 2-year longitudinal study on clinical features & biomarkers in LRRK2 non-manifesting carriers (n=175; vs 185 controls) observes no changes in any clinical measures over 2 years or in DAT binding (urinary BMP was increased thru out, but did not change). Remember these individuals do not have Parkinson’s, they are simply non-manifesting LRRK2 variant carriers (Click here to read more about this).
• In a large cohort of women with a long follow-up, obesity was associated with a lower hazard of Parkinson’s – even when measured 20 years before diagnosis – in agreement with Mendelian randomization studies; N=96K women (age=40-65 yrs), 1,164 developed PD (Click here to read more about this).
• Using worldwide registry data, researchers report “a striking rising trend in Parkinson’s disease mortality globally. Persistent age & sex disparities are found in PD mortality trends” (Click here to read more about this).
• Recent medrxiv manuscript presents the results of a questionnaire that addresses female specific experiences & their Parkinson’s clinical history; Modeling highlights significant associations (Click here to read more about this).

• Recent medrxiv manuscript reports increased brain & systemic inflammation (TSPO brain imaging) in de novo Parkinson’s patients compared to controls; Longitudinal follow-up will be important (Click here to read more about this).
• Wrist actigraphy enables home screening of Rapid Eye Movement Behavior Disorder in Parkinson’s (Click here to read more about this).
• Using former carers’ expertise in peer support for carers of people with Parkinson’s (Click here to read more about this).
• Small study (N=2750, January 1950 to December 2007), but premenopausal bilateral oophorectomy was found to be associated with an increased risk of parkinsonism; A “pattern of increasing risk with younger age” (Click here to read more about this).
• A new 31-phosphorus magnetic resonance spectroscopy study finds that mitochondrial dysfunction & bioenergetic depletion contribute to idiopathic Parkinson’s (N=30) pathophysiology, but NOT to progressive supranuclear palsy (PSP; N=16); N=25 controls (Click here to read more about this).
• Researchers propose a multimodal data approach (including gait acceleration, electroencephalogram (EEG), electromyogram (EMG), & skin conductance) for the detection of freezing of gait in Parkinson’s (Click here to read more about this).
• Can voice tracing provides insights for early diagnosis & monitoring of the evolution of Parkinson’s? New study explores mixed kernel support vector regression models…and I’m not even going to try & pretend I know what that means! (Click here to read more about this).

• Further observations from the LEAP (“Levodopa response in patients with EArly Parkinson’s”) study: At 80 weeks there were fewer patients with motor response fluctuations in the group that had started levodopa earlier. Also “the effect of levodopa on bradykinesia, rigidity & tremor is larger after 22 weeks compared to four weeks of treatment” (Click here to read more about this).
• Using 18F-FP-CIT PET scan data from 240 individuals newly diagnosed with Parkinson’s, researchers explore whether the pattern of striatal dopamine depletion is associated with white matter networks (Click here to read more about this).
• The “present results underline the high risk of dementia in Parkinson’s & further emphasize the importance of developing symptomatic & ultimately disease modifying strategies to counteract this part of the non-motor symptomatology in PD” (Click here to read more about this).
• The benefits of a new clinic study were “noticeable to the participants themselves, as most (20/26 participants, or 77%) requested to continue choir participation after the completion of the study. The ParkinSonics choir continues to meet weekly” (Click here to read more about this).
• The protocol for the Mobilise-D clinical validation study has been published. This is a longitudinal observational cohort study that will recruit 2400 participants from four clinical cohorts (Parkinson’s included). Consortium=34 partners from 13 countries (Click here to read more about this).

• New paper presents the protocol for a pilot feasibility & acceptability study of technological visuo-cognitive training in Parkinsons; 4-week intervention involving 40 PwP; Senaptec (Click here to read more about this).
• Researchers publish the study protocol of a randomized controlled trial to determine if combining repetitive transcranial magnetic stimulation & video game-based training can improve dexterity in Parkinson’s (Click here to read more about this).
• PARS study researchers assessed 186 individuals who were initially hyposmic, during ~10 yr follow up 28% reverted & only 2% of these ‘reverters’ developed Parkinson’s, vs 20% of those with persistent hyposmia who developed PD (Click here to read more about this).
• A systematic review of brain morphometry related to deep brain stimulation outcome in Parkinson’s finds that reduced cortical thickness/brain volume of motor cortex & thalamus are associated with less motor improvement (Click here to read more about this).
• An analysis of a large Parkinson’s cohort revealed structural alterations in the substantia nigra & putamen can be measured by diffusion microstructure imaging; Alterations=associated with poorer motor performance in ON-state & reduced response to levodopa (Click here to read more about this).
• Neuromelanin-MRI & T2* MRI with radiomics analysis highlights group differences in 127 study participants (46 Parkinson’s cases: 15 LRRK2-PD, 16 GBA-PD, & 15 iPD; 47 non-manifesting variant carriers & 34 non-carrier controls; Notes iron accumulation (Click here to read more about this).
• A study reported fecal microbiome alterations in treatment-naive de novo Parkinson’s in 2 large independent case-control cohorts; No differentially abundant taxon replicated in both cohorts, but SCFA taxa decreased in both cohorts (Click here to read more about this).

• A single-center longitudinal study (58 drug-naïve PD patients & 58 matched controls) finds lymphocyte count (lower) & neutrophil-to-lymphocyte ratio (higher) were associated with mild cognitive impairment in Parkinson’s (Click here to read more about this).
• New paper finds resting brain states defined not only by amplitude modulation dynamics but also by frequency modulation dynamics of neuronal oscillations; Subthalamic beta oscillations encode dopaminergic state in Parkinson’s (Click here to read more about this).
• New paper finds alternating spectral changes between the hemispheres of the brain in accordance with the gait cycle; Also identifies patient-specific, gait-related biomarkers in both the STN & cortical areas – implications for adaptive DBS in Parkinson’s? (Click here to read more about this).
• Small study, but researchers report a weak, but statistically significant, association between LAG3-related CD4 molecule gene polymorphisms (rs1922452 & rs951818) & the risk of Parkinson’s in a Caucasian Spanish population (N=629 PD & 865 controls – click here to read more about this).
• A systematic review and network meta-analysis of efficacy & evaluation of therapeutic exercises on individuals with Parkinson’s; “Low quality evidence” for power training, yoga, body weight support treadmill training, dance & resistance training (Click here to read more about this).

• New study reveals “a resting-state regional spontaneous neuronal reorganization in newly-diagnosed drug-naïve patients with Parkinson’s” highlighting the potential value of fractional amplitude of low-frequency fluctuations derived from resting-state-fMRI (Click here to read more about this).
• New research explores upper-extremity kinematics & interlimb movement in people with Parkinson’s on irregular terrain, cross-slope, & under dual-task condition; PwP increase arm swing magnitude when balance is challenged (Click here to read more about this).
• Using a systematic screening approach in a nationwide nested case–control study, researchers identify drugs associated with lower risk of Parkinson’s; Antipsoriatics & antigout medications stand out (Click here to read more about this).
• A nationwide population-based study (Taiwan, 2000-2013) with Helicobacter pylori infection were associated with an increased risk for sleep-related movement disorders, with a higher risk in men, aged ≥65 years & diagnosed for more than 5 years (Click here to read more about this).
• The potential clinical & economic benefits of remote deep brain stimulation programming for people with Parkinson’s, dystonia, & essential tremor in Hungary (Click here to read more about this).

• New research applied RT-QuIC to salivary samples from 37 de novo Parkinson’s patients & 23 sex/age-matched controls; 86% of the PD were deemed RT-QuIC positive vs 22% of the controls (Click here to read more about this).
• An interview study explores patients’ views on using human embryonic stem cells to treat Parkinson’s; “There are some concerns that the industry will not always prioritise the patient over profit. Transparency is therefore seen as vital” (Click here to read more about this).
• Two decades of clinical trial data (n=3238 trials) used to analyze the characteristics of trials across 4 major neurodegenerative conditions (Alzheimer’s, Parkinson’s, ALS & Huntington’s); “Our findings suggest the risk of a missed opportunity” (Click here to read more about this).
• Thiazolidinedione use is associated with a decreased risk of Parkinson’s incidence in a mainland Chinese population with type 2 diabetes mellitus (Click here to read more about this).
• New report proposes that “Short-term Parkinson’s progression can be predicted with a combination of survey-based, neuroimaging, physician exam, & genetic predictors”; PPMI cohort for training & PDBP for testing (Click here to read more about this).
• New research finds no evidence to support the association of the excess burden of heterozygous private variants in PRKN, PARK7, & PINK1 with Parkinson’s risk in the European population (N=15K+ vs 55K+ controls – click here to read more about this).
• The rationale for the ‘Stimulation of the Tibial nerve Repetitively to improve Incontinence in Parkinson’s Electronically‘ (STRIPE) study – a randomised control trial involving a self-contained wearable device (Click here to read more about this).
• PPMI cohort data indicates weight loss in recently diagnosed Parkinson’s patients is associated with a faster progression in global cognitive decline & executive function; Early weight gain associated with a slower decline in processing speed & attention (Click here to read more about this).

• Small study, but interesting: Could speech acoustic indices provide differential diagnosis between Parkinson’s (n=25), multiple system atrophy (MSA; n=20) & progressive supranuclear palsy (PSP; n=20); Pilot study suggests yes between MSA & PSP (Click here to read more about this).
• Proinflammatory profile in the skin of people with Parkinson’s with & without pain demonstrate a higher expression of cutaneous IL-2 & TNFα in patients with PD (vs controls) independent of skin innervation & pain phenotype (Click here to read more about this).
• New research finds changes in iron & oxygen homeostasis-related gene expression associated with CNS aging, & identifies dysregulated expression of rare NBIA genes associated with tau pathology – distinguishing PSP from controls (Click here to read more about this).
• Multiple input algorithm-guided Deep Brain stimulation-programming for Parkinson’s – “an important step for future closed-loop DBS optimization systems” (Click here to read more about this).
• A systematic review & meta-analysis on effects of aerobic exercise in people with Parkinson’s finds “beneficial effects in improving balance, gait (velocity and stride/step length), & motor function”, but not step cadence & quality of life (Click here to read more about this).

• Could free water values in the posterior substantia nigra be a progression imaging marker of early dopaminergic degeneration in the population at risk of Pakinson’s? New study followed asymptomatic LRRK2 G2019S carriers over time (Click here to read more about this).
• New research presents the first study to carry out a quantitative assessment of cell loss, alpha-synuclein pathology, & inflammation in the substantia nigra & subthalamic nuclei of Parkinson’s patients with/without STN-DBS (Click here to read more about this).
• New paper shares their process for developing a clinical trial-ready Multiple System Atrophy (MSA) cohort within an outpatient setting; Deep phenotyping (including MRI, MIBG scan, polysomnography, genetic testing, skin biopsy,…). They propose their integrative clinic & longitudinal deep phenotyping approach “will not only facilitate more seamless recruitment of MSA patients into such studies, but engender a deeper biological understanding of the nature of this complex & devastating disease” (Click here to read more about this).
• The protocol for the “Study in Parkinson’s of exercise phase 3 (SPARX3)” has been published. This is a randomized controlled trial to determine the efficacy of high-intensity, endurance treadmill exercise on PD progression (as measured by the MDS-UPDRS 3 – click here to read more about this).

New clinical trials

• New clinical trial registered: A dose-blinded extension study to evaluate the long-term efficacy, safety, & tolerability of UCB0599 (a small-molecule α-synuclein aggregation inhibitor) in NCT04658186 study participants with Parkinson’s (Click here to read more about this).
• New clinical trial registered: An open label extension of the NOPARK study (NCT03816020) evaluating nicotinamide riboside in Parkinson’s (N=400, time frame: 0-3 years – click here to read more about this).

• New clinical trial registered: The N-DOSE study is a double-blinded placebo-controlled randomized trial aiming to determine the optimal biological dose of nicotinamide riboside in 80 individuals with Parkinson’s (Click here to read more about this)
• New clinical trial registered: InSightec has registered a two-arm, open-label study to establish safety & feasibility of intracerebral delivery of GCase (via MR-guided focused ultrasound) in 14 individuals with Parkinson’s (7 GBA-PD & 7 iPD – click here to read more about this).
• New clinical study registered: An investigation of aromatic L-amino acid decarboxylase (AADC) & tyrosine decarboxylase activity (+ the gut microbiome) in 50 individuals with advanced Parkinson’s (Click here to read more about this).
• New clinical trial registered: A pilot data exploring the therapeutic benefits of self-administered rehabilitation games among 20 individuals with Parkinson’s (“Serious Games for PD” – click here to read more about this).

Clinical trial news

• Clene Nanomedicine announced topline results showing a survival benefit in the Healey ALS Platform trial of CNM-Au8 (an investigational gold nanocrystal suspension) in participants with amyotrophic lateral sclerosis (ALS). The primary endpoint (ALSFRS-R) and secondary endpoints (CAFS and SVC) were not met at 24 weeks, but prespecified exploratory analyses were encouraging (Click here to read more about this)

• Adiso Therapeutics has provided an update on their pipeline which includes ADS024 (an oral single strain live biotherapeutic product based on Bacillus velezensis strain which selectively kills C. difficile) for Parkinson’s; Rescues PD models (Click here to read more about this).

Conferences/lectures

• Nothing this month

Other news

• Biotech companies Biogen & Denali Therapeutics announce dosing has commenced in their Phase 3 LIGHTHOUSE study of 400 participants with Parkinson’s & LRRK2 pathogenic variants, to evaluate the efficacy & safety profile of the LRRK2 inhibitor BIIB122 (aka DNL151 – click here to read more about this).

• A research team Icahn Mount Sinai has been selected to receive the 2022 Parkinson’s Foundation Research Center Award, totaling $2 million; The team aims to conduct deep profiling of cell diversity in a PD-associated brain region called the substantia nigra (Click here to read more about this).
• The University of Illinois has partnered with Amazon, Apple, Google, Meta, Microsoft & nonprofits on the Speech Accessibility Project to improve voice recognition for communities with disabilities & diverse speech patterns often not considered by AI algorithms (Click here to read more about this).
• The US FDA informed Supernus that they agreed to review the filing for their apomorphine infusion pump for Parkinson’s but then identified a need for additional information and analyses (Click here to read more about this).
• Muna Therapeutics has been awarded a $4.9 million grant from the Michael J Fox Foundation to support development of novel, small molecule potassium channel type 1.3 (Kv1.3) blockers for Parkinson’s (Click here to read more about this).

• Lucy Therapeutics presented data on their two lead small molecule agents, LucyTx-1209 & LucyTx-1212 (which target the F1F0-ATPase protein complex) at the Michael J Fox Foundation’s 14th annual Parkinson’s Disease Therapeutics Conference (Click here to read more about this).
• RNA-editing. All the cool kids are doing it! It’s the “Shape Therapeutics” of things to come… And it could have implications for Parkinson’s (Click here to read more about this).
• Verge Genomics has initiated dosing in their Phase 1 trial of VRG50635 – a novel therapeutic discovered & “delivered into the clinic in just 4 years” by an AI-powered platform. VRG50635 is a small molecule inhibitor of PIKfyve for ALS (Click here to read more about this).

• Alterity Therapeutics launches a randomized, double-blind, placebo-controlled trial of their iron chelator ATH434 in patients with early-stage Multiple System Atrophy (MSA); N=60 participants who will be treated for 12 months (Click here to read more about this).
• Parkinson’s UK are investing £2 million in Enterin’s Phase 2 clinical trial of its drug ENT-01 – a potential treatment for Parkinson’s dementia; They plan to launch a placebo-controlled Phase 2b study in the UK & US in 2023 (Click here to read more about this and click here to read the press summary of this announcement).
• Parkinson’s UK announced that over the last 2 years, their Vivifi Biotech company has made progress towards a clinical trial that aims to advance GDNF for Parkinson’s (Click here to read more about this).

Review articles/videos

And there it is, just some of the highlights from October 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 November!!!

All of the material on this website is licensed under a
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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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