Monthly Research Review – July 2018

~ Simon

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 July 2018.

The post is divided into five parts based on the type of research (Basic biology, disease mechanism, clinical research, other news, and Review articles/videos). 

So, what happened during July 2018?

In world news:

July 1-31st – Best summer weather ever in the UK (personal opinion based on 12 years experience)

July 7 – Fifty three couples lined up for the 23rd Annual Wife Carrying Championship (?!?). The hour-long race in the small Finnish town of Sonkajarviwas was won by a Lithuanian couple (congrats to Vytautas Kirkliauskas and his wife Neringa Kirkliauskiene). The image below is from one of the UK contests (looks like pretty serious stuff, huh?).

July 10 – Twelve boys and their football coach are successfully rescued from the flooded Tham Luang Nang Non cave in Thailand, following a 17-day ordeal that gained worldwide attention.

July 25 – Scientists report the discovery of a subglacial lake on Mars, 1.5 km below the southern polar ice cap. The lake, extending out about 20 km, is the first known body of water on the planet.

July 27 – The longest total lunar eclipse of the 21st century occurred, and Mars makes its closest approach to Earth since 2003.

 

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

In July 2018, there were 645 research articles added to the Pubmed website with the tag word “Parkinson’s” attached (4751 for all of 2018 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. Immune system:

New evidence for a role in the adaptive immune system in Parkinson’s. Researchers found an increase in a particular type of immune cell (T-cells) in post mortem section of brain from people with PD. They also found a high level of one particular type of T-cell (IL-17-producing helper T-cells) in PD blood (compared to healthy control sample). These T-cells induce cell death in cell culture. Blocking of IL-17 or the addition of the FDA-approved anti-IL-17 antibody, secukinumab, rescued the neuronal death – Secukinumab is FDA approved for the treatment of moderate-to-severe plaque psoriasis ( to read more about this and click here to read a SoPD post on this topic).

2. Tiny treatment?

New study reports that graphene quantum dots possess unique neuroprotective effects in alpha synuclein preformed fibrils model of Parkinson’s. They can penetrate the blood–brain barrier & bind to alpha synuclein preformed fibrils preventing their toxicity ( to read more about this,  to read a SoPD post on this topic, and click here to read the press release).

 

3. Voyager Therapeutics update

The biotech firm has receives FDA guidance regarding the development path for their gene therapy treatment (VY-AADC) that is being clinically trialled for Parkinson’s. Also provided clinical update for the Phase 1 posterior trajectory trial ( to read the press release and click here to read a SoPD post on this topic).

4. A wider role for LRRK2?

Researchers find that, independent of any mutations, Leucine-rich repeat kinase 2 (or LRRK2 – pronounced ‘lark 2’) may play a role in idiopathic Parkinson’s. Meaning: the LRRK2 kinase inhibitors being developed could be useful for treating PD in people without LRRK2 mutations ( to read more about this, Click here to read a press release about this research, and click here to read an SoPD post on this topic)

5. Japanese Stem Cell transplantation trial

Prof Jun Takahashi & colleagues at University of Kyoto (Japan) announced that they have been given permission from regulators to start the world’s first clinical trial of cells derived from induced pluripotent stem (iPS) cells on Parkinson’s next month ( to read more about this).

 

Basic biology news

  • A protein called mesencephalic astrocyte-derived neurotrophic factor (MANF) has been found to reduce protein aggregation, restore dopamine levels & rescue the function of dopamine neurons in an alpha synuclein model of Parkinson’s ( to read more about this).
  • Researchers report that glycosaminoglycans – integral components of the extracellular matrix surrounding a neuron – are key modulators in Parkinson’s-associated alpha synuclein amyloid formation, & their distinct activities are important ( to read more about this).
  • Researchers find that blackberry (Morus nigra) fruit juice is effective to reducing L-dopa induced dyskinesias in a mouse model of Parkinson’s ( to read more about this).
  • Researchers also found that Alaskan bog blueberry (Vaccinum uliginosum) polyphenols mediate inhibition of sir-2.1 protein which reduced alpha synuclein protein in a model of Parkinson’s ( to read more about this).

  • Researchers suggest that subpopulations of striatonigral neurons are involved in adaptations induced by dopamine replacement therapy in Parkinson’s ( to read more about this).
  • Scientists have developed a computational platform (TransSyn) for identifying synergistic transcriptional cores that determine cell subpopulation identities. Major implications for the generation of dopamine neurons for Parkinson’s ( to read more about this).
  • Mice with no RESP18 protein display reduced locomotor activity & motor coordination, but they are more resistant to neurotoxins in models of Parkinson’s. The activation of glial cells was inhibited in these mice ( to read more about this).
  • New manuscript on Biorxiv introduces near-infrared catecholamine nanosensors (nIRCats) as a non-genetically encoded method of observing dopamine release in tissue ( to read the manuscript).
  • Another study demonstrating inhibition of hepatic NLRP3 inflammasome weakens inflammatory cytokines spreading into the brain & delays the progress of neuroinflammation & dopamine neuron loss in a mouse model of Parkinson’s (MPTP-  to read more about this).
  • Glial cell line-derived neurotrophic factor (GDNF) has two forms (isoforms): full-length α-GDNF & a shorter β-GDNF. β-GDNF is less well studied. New research suggests that both isoforms have comparable neuroprotective efficacy in models of Parkinson’s ( to read more about this).
  • Interesting manuscript in Biorxiv – researchers report that Parkinson’s-associated glucocerebrosidase (GCase) directly inhibits lipid-induced alpha synuclein aggregation & also destabilises mature alpha syn. fibrils ( to read the manuscript).
  • 7-month-old Tau knockout mice lose their sense of smell (hyposmia) which correlates with accumulation of Parkinson’s-associated alpha synuclein in the olfactory bulb. The feature becomes apparent in the striatum & substantia nigra at 15-months of age ( to read more about this).
  • The enzymatic core of the Parkinson’s-associated protein LRRK2 does not affect mitophagic degradation but globally impairs mitochondrial biogenesis in aging yeast (by selectively compromising complex IV formation –  to read more about this).
  • Researchers report conversion of human skin cells into pluripotent stem cells, by activating the cell’s own genes using CRISPR – implications for Parkinson’s cell transplantation & personalised medicine ( to read more about this and click here to read the press release).
  • A systematic review of 231 research articles recommends that the therapeutic benefits of vitamin D cannot be made for neurodegenerative conditions like Parkinson’s & Alzheimer’s. “It is unclear if vitamin D mediates a protective benefit” ( to read more about this, and click here to read the press release).

  • PICK1 inhibits the activity of Parkinson’s-associated protein PARKIN and reduces its neuronal protective effect. Mice with no PICK1 are resistant to neurotoxin used in PD models ( to read more about this).
  • New manuscript on biorxiv reports that a dopamine metabolite binds directly to & modulates the activity of Nuclear receptor related 1 protein (NURR1), highlighting new avenues for developing synthetic Nurr1 activators for Parkinson’s ( to read this manuscript).
  • NRF2 is a key regulator of antioxidant defense systems, & pharmacological activation of this protein is a promising strategy for Parkinson’s. New research finds that over-activation of NRF2 is not only promotes senescence, but also pro-tumorigenic. Constitutive activation of NRF2 promotes accelerated wound closure, but also tumorigenesis – Researcher’s conclusion: “These data highlight the bright and the dark sides of NRF2 and the need for time-controlled activation of this transcription factor” ( to read more about this).
  • A large analysis of off-target changes made by CRISPR-Cas9 gene editing by Sanger Institute researchers suggests repair of double-strand breaks induced by CRISPR leads to large deletions & complex rearrangements. Implications for Parkinson’s research? ( to read more about this and click here to read the press release).
  • α-methyl-α-phenylsuccinimide – the active metabolite of an approved antiepileptic drug, methsuximide – has been reported to have neuroprotective properties in models of TDP-43 proteinopathy. Implications for Parkinson’s? ( to read more about this and click here for the press release).
  • New study on biorxiv suggests that misfolded TAU protein is efficiently passed between individual neurons, but it is not immediately toxic to neurons. Implications for Alzheimer’s & Parkinson’s? ( to read the manuscript).
  • New study suggests that cannabidiol treatment, which has been proposed as a treatment for anxiety in Parkinson’s, does not display drug abuse potential in mice behaviour ( to read more about this).
  • Researchers hypothesized that inhibition of autophagy would aggravate Parkinson’s-associated alpha synuclein-induced cell death. They were wrong. It increased the secretion of alpha synuclein via exosomes. Exosomal secretion is a protective mechanism? ( to read more about this).

  • The rescue of a lysosomal storage disorder in mice using ex vivo correction of a genetic mutation, raises the possibility of similar approaches for conditions like GBA-associated Parkinson’s ( to read more about this).
  • An independent researcher has investigated & written a report (which is available on biorxiv) regarding blood-brain barrier penetrance assessment of dietary supplements & drugs for potential treatment of Parkinson’s ( to read the manuscript).
  • New data suggest that Parkinson’s-associated LRRK2 can promote microglial mitochondrial alterations via Drp1 (in a kinase-dependent manner), resulting in stimulation of pro-inflammatory responses. Rescued by treatment with the LRRK2 inhibitor, GSK2578215A ( to read more about this).
  • Further evidence that mitochondrial biogenesis occurs not only in cell bodies, but also in distal axons: Mitochondrial DNA replication increases in distal axons in the early stages of Parkinson’s ( to read more about this).
  • New manuscript on biorxiv suggests Parkinson’s-associated PARKIN genetic mutations may impair glutamatergic synaptic transmission & plasticity by impeding NMDA & AMPA receptor trafficking ( to read the manuscript).
  • Researchers deconstruct the cue-elicited behaviours generated by different populations of dopamine neurons, improving our understanding of Pavlovian conditioning. Perhaps value of reward-associated cues needs to be reassessed in people with Parkinson’s ( to read more about this).
  • Acoustically Targeted Chemogenetics (ATAC). Researchers combine ultrasound, gene therapy, & synthetic drugs to noninvasively control the brain – implications for Parkinsons? ( to read more about this, and click here to read the press release).

  • New research suggests that an oxidative insult is contained locally to the damaged region of a neuron. ATP levels (energy) decrease only in the damaged region while increasing in the regions distal to the insult. Implications for Parkinsons? ( to read more about this).
  • Loss of Synapsin III protein hampers Parkinson’s-associated alpha synuclein aggregation & dopamine cell loss in an AAV-based mouse model of PD ( to read more about this).
  • Super‐resolve techniques find that neuronal cells derived from people with Parkinson’s contain a larger number of protein aggregates than those from healthy controls ( to read more about this).
  • New study provides molecular insight into the fibrillar assembly of Parkinson’s-associated alpha synuclein protein at the atomic level & sheds light on the molecular pathogenesis caused by familial mutations ( to read more about this).
  • Researchers have published a report presenting the structure of Parkinson’s-associated cytotoxic alpha-synuclein fibrils (residues 1-121), determined by cryo-electron microscopy at a resolution of 3.4 ångströms! ( to read the research report).

 

Disease mechanism

  • Researchers report that eukaryotic elongation factor-2 kinase (eEF2K) activity is increased in postmortem Parkinson’s brains & inhibiting eEF2K protein prevented the toxicity associated with alpha synuclein protein aggregation. “These data suggest a role for eEF2K activity in AS toxicity, and support eEF2K inhibition as a potential target in reducing AS-induced oxidative stress in Parkinson’s” … “development of novel eEF2K inhibitors is actively being pursued towards experimental therapies in cancer” ( to read more about this and  to read a SoPD post on this topic).
  • Microglia – the brains resident immune cells – have 2 states: proinflammatory M1 & anti-inflammatory M2 state. Researchers find that modulation of M1/M2 polarization by capsaicin contributes to the survival of dopaminergic neurons in a model of Parkinson’s ( to read more about this).
  • EMD 281014, a selective serotonin 5-HT2A receptor antagonist, reduces psychosis & also L-DOPA-induced dyskinesia in a primate model of Parkinson’s without interfering with L-DOPA anti-parkinsonian action. “EMD-281,014 was tested in the clinic (Mamo et al., 2004 – ), and was reportedly well tolerated. However, its development seems to have been discontinued, for reasons that were not disclosed” ( to read more about this).
  • Researchers have a manuscript on Biorxiv which shows how common genetic variations in the mouse alpha synuclein gene (SNCA) may help explain modulate Parkinson’s risk in humans ( to read the manuscript).
  • MANF Therapeutics announces that the results of a MANF pre-clinical study suggest beneficial effects in an alpha-synuclein-based model of Parkinson’s. ER stress and autophagy pathways are involved in MANF-mediated neuroprotection ( to read more about this and click here for the press release).

  • Neuronal cells derived from people with sporadic Parkinson’s help to elucidate novel disease mechanisms & provide insights into the epigenetic landscape of PD, particularly the importance of small/micro RNAs ( to read more about this).
  • Hypertension drugs Candesartan and Telmisartan (both angiotensin type 1 blockers) prevent changes in microglial (the immune cells of the brain) & dopaminergic neuron cell death in an alpha synuclein model of Parkinson’s. New drugs for re-purposing? ( to read more about this).
  • The toxic form of Parkinson’s-associated alpha synuclein (oligomers) induces early axonal dysfunction in human iPSC-derived neurons, via disruption of anterograde transport of mitochondria, & results in synaptic degeneration. A need for early intervention? ( to read more about this).
  • French researchers provide insights into how glucocorticoid receptors on astrocytes (the helper cells the brain) regulate dopamine neuron degeneration (via connexin hemichannel) in models of Parkinson’s. Deregulation of astrocytes amplifies inflammation ( to read more about this).
  • Does Tau protein aggregation induce cellular senescence? New manuscript on biorxiv suggests yes, & postmortem analysis indicates phenomenon may be common across neurodegenerative conditions. Implications for Parkinson’s? ( to read the manuscript).
  • Prolyl Oligopeptidase (or PREP) derived from activated microglia could be a neuroprotection target for Parkinson’s & Alzheimer’s. PREP inhibitor KYP‐2047 protected neurons against microglial toxicity & reduced levels of the pro‐inflammatory cytokine TNFα ( to read more about this).

  • Natural histone acetyltransferase inhibitors (such as anacardic acid, garcinol, and curcumin) reduce L-DOPA-induced dyskinesia in a mouse model of Parkinson’s. Additionally, l-DOPA’s efficacy was not altered at early stage of treatment ( to read more about this).
  • Further evidence that human embryonic stem cells patterned to dopamine fate & transplanted into the substantia nigra show the capacity to progressively innervate correct forebrain targets over time in a model of Parkinson’s ( to read more about this).
  • The surface of cells have chains of sugar-protein molecules that help the cell to absorb things. Researchers have found that specific patterns in those chains are required for cells to take up Tau VS Parkinson’s-associated α-synuclein & Alzheimer’s β-amyloid aggregates ( to read more about this and click here for the press release).
  • Researchers expand our knowledge of polymorphism in Parkinson’s-associated alpha synuclein protein fibrils, important information for the designing of drugs to inhibit the aggregations of this protein ( to read more about this).
  • Another GLP-1 agonist (similar to Exenatide) demonstrates beneficial effects in models of Parkinson’s. Researchers present PT302, a long-acting (once every 2 weeks) GLP-1 agonist ( to read more about this).
  • And yet another GLP-1 agonist (similar to Exenatide) demonstrates neuroprotective effects in a mouse model of Parkinson’s. Researchers tested Novo Nordisk’s long acting GLP-1 agonist – Semaglutide – and found it to be superior to Liraglutide. Motor activity,inflammation & autophagy were normalized in the mice ( to read more about this).

  • New report introduced AAV2-HBKO – a powerful new viral vector for the potential treatment of a wide number of neurological disorders, like Parkinson’s ( to read more about this).
  • A new analysis reveals significant alterations in the representation of certain bacteriophages in people with Parkinson’s suggesting that gut phagobiota composition may serve as a diagnostic tool or even a possible target for therapeutic intervention ( to read more about this).
  • Researchers suggest that recognition, ubiquitination & destruction of Parkinson’s-associated alpha-synuclein filaments may protect cells against the toxic forms of the protein. But A53T alpha-synuclein may be more toxic because it avoids this fate ( to read more about this).
  • Nav 1.6 is a channel that is present in activated microglia. Zonisamide – an epilepsy & PD medication – decreases microglial Nav 1.6. New research suggests that Zonisamide reduces neuroinflammation in a model of Parkinson’s ( to read more about this).
  • Spanish researchers report that targeting the protein kinase CK-1δ may be a new mechanism of action to modulate the cell death observed in models of Parkinson’s ( to read more about this)
  • Fuz – a planar cell polarity protein – is found to triggers neuronal cell death in multiple models of neurodegeneration. Fuz levels are elevated by alpha synuclein aggregation, implicating its potential involvement in Parkinson’s ( to read more about this).
  • New research demonstrates that truncation of Parkinson’s-associated alpha synuclein protein can influence its prion-like pathogenicity, resulting in phenotypic diversity of α-synucleinopathies ( to read more about this)
  • Further evidence of beneficial effects of Ambroxol treatment in a model of Parkinson’s – it modulates neurotoxin-induced temporal reduction in Glucocerebrosidase enzymatic activity, and helps to protect against cell loss & mitochondrial dysfunction ( to read more about this).

  • Researchers show that different alpha synuclein & beta synuclein genetic variations may be associated with the development of either Parkinson’s or Lewy body dementia (DLB –  to read more about this).
  • A case-controlled cohort study screened 11 095 people with Parkinson’s & 12 615 controls for “loss of function” genetic variants in LRRK1 & LRRK2 genes. No significant enrichment in cases with PD was found compared with controls ( to read more about this).
  • Corilagin – a polyphenol & hydrolyzable tannin – reduces the effects of Japanese encephalitis virus-induced Parkinson’s in animal models ( to read more about this).
  • In vivo & in vitro results reveal that the cellular stress mediated by Parkinson’s-associated alpha-synuclein protein aggregation elicits DNA damage & activates the DNA damage response. Administration of the antioxidant NAC reduces the effect ( to read more about this).
  • LRRK2 with the G2019S genetic variant induces Parkinsonian-like pathology in a nonhuman primate brain ( to read more about this).

  • Yet more on LRRK2: Protein levels of Parkinson’s-associated LRRK2 increased significantly in brain tissues in a rodent model of stroke, reducing those levels using a LRRK2 inhibitor via a p-38 MAPK/Drosha pathway ( to read more about this).
  • And again: LRRK2 -While “WT-LRRK2 kinase activity could be completed blocked without lowering LRRK2 protein levels, higher inhibitor concentrations were necessary to fully reduce G2019S-LRRK2” – interesting report on chronic Parkinson’s-associated LRRK2 inhibitor treatment ( to read more about this).
  • Interesting idea: A user-friendly herbicide derived from photo-responsive supramolecular vesicles – herbicide is only released upon UV or sunlight irradiation. No more pesticide exposure-associated Parkinson’s? ( to read more about this).
  • Researchers present evidence of encapsulation of dopamine grafts in a GDNF‐loaded collagen hydrogel increasing the survival, re‐innervation & functional efficacy after transplantation into a model of Parkinson’s ( to read more about this).

 

Clinical research

  • The term ‘advanced Parkinson’s‘ is applied in distinctively to individuals with long PD duration. Now the CDEPA questionnaire (“Cuestionario De Enfermedad de Parkinson Avanzada” [Questionnaire for Advanced Parkinson’s]) provides a simple screening tool for advanced PD ( to read more about this).
  • Could theophylline – a caffeine metabolite – be used as a biomarker for Parkinson’s? Japanese researchers suggest yes, & present data confirming previous findings of significantly lower levels of serum theophylline in people with PD (vs healthy controls) ( to read more about this).
  • Hyperhomocysteinemia = abnormally high level of homocysteine (hcy) in the blood. People with Parkinson’s are at a risk of hyperhomocysteinemia. Physical activity decreases Hcy level, whereas poor motor function increases it ( to read more about this).
  • Stomach/colon biopsies from 35 people with Parkinson’s & 52 control subjects finds deposition of alpha synuclein protein in the mucosal enteric nervous system may not reflect functional impairment of the affected segment of the gut ( to read more about this).
  • Researchers provide a neuropsychological assessment for the screening of candidates for deep brain stimulation in Parkinson’s, & identify baseline risk factors, which requires careful consideration before & after surgery ( to read more about this).
  • Use of domperidone – a peripherally selective dopamine D₂ receptor antagonist – has been associated with a 2x increased risk of mortality in people with Parkinson’s (vs people with PD who never used domperidone). Risk is highest in first month of use ( to read more about this).

  • Japanese researchers propose a new device-aided cognitive function test – “User eXperience-Trail Making Test” (UX-TMT) – which sensitively detects neuropsychological performance in people with dementia & Parkinson’s ( to read more about this).
  • A revised manuscript on biorxiv presents ‘Lead-DBS v2‘: an open source toolbox providing a comprehensive pipeline for deep brain stimulation imaging & connectomics. Major implications for Parkinson’s ( to read the manuscript).
  • New Biorxiv manuscript reports a genetic screen for the Parkinson’s-associated p.G2019S LRRK2 variant in a large cohort of 126 people with PD & 55 controls from Nigeria. ALL of the participants in the study are negative for the p.G2019S mutation ( to read more this manuscript).
  • Japanese researchers find that explicit learning of visuomotor sequences is preserved during Parkinson’s progression. “Even patients with severe PD can learn visual sequences and can translate them into visuomotor sequences” – implications for rehab ( to read more about this).
  • A nationwide retrospective observational study from Taiwan finds that people with nephrotic syndrome (resulting from kidney damage) have an increased risk of Parkinson’s. Increased risk may be due to brain vascular damage or blood–brain barrier impairment ( to read more about this).
  • Korean researchers find that people with diabetic retinopathy are at a higher risk of developing Parkinson’s ( to read more about this).
  • LRRK2-G2019S is a common Parkinson’s-associated genetic variant. New study suggests that Tunisian G2019S carriers have a more benign form of PD than non-carriers. Cognitive issues & depression are less common in G2019S males compared with females ( to read more about this).

  • Researchers propose new anatomo-clinical atlases to visualise the motor & neuropsychological consequences at 6 months after subthalamic nucleus or pallidal deep brain stimulation in people with Parkinson’s. No significant neuropsych impairments ( to read more about this).
  • Researchers report evidence from blood analysis of 82 people with PD & 47 controls that strengthens the idea of a peripheral adaptive immunity involvement in Parkinson’s. β2-AR agonists (like salbutamol) represent “candidates to be tested on CD4+ T cells from PD patients 4 their ability to correct dysfunctional responses such as Th1-biased differentiation of CD4+ naïve T cells & increased production of Th1 cytokines insensitive to Treg inhibition” ( to read more about this).
  • 66% of people with Parkinson’s are estimated to have some loss of sympathetic innervation to the heart at diagnosis. New study suggests that radioligands hold potential as in vivo biomarkers of mechanisms of cardiac neurodegeneration & neuroprotection in Parkinson’s ( to read more about this).
  • An analysis of monocyte blood cells from people with recently diagnosed Parkinson’s (vs controls) highlights a distinct pattern of gene expression in monocytes (HLA-DQB1, MYD88, REL, & TNF-α). Future studies of distinct leukocyte subsets are warranted ( to read more about this).
  • In a survey of 20,591 male farmers between 2013–2015, 7.8% reported dream enacting behaviour during REM sleep, which is a characteristic feature of REM sleep behaviour disorder (RBD) – one of the most specific prodromal symptoms for Parkinson’s ( to read more about this).
  • A new study of 13,708 people with Parkinson’s & 95,282 controls finds no evidence for a causal relationship between urate & Parkinson’s. No evidence for a linear causal protective effect by urate on PD risk. Strategies to elevate urate levels may not reduce PD risk ( to read more about this).
  • Researchers test the protein propagation hypothesis of Parkinson’s using human neuroimaging from the PPMI database. They find that the progression of brain atrophy follows neuronal connectivity & they identify an epicenter in the brain stem ( to read more about this).
  • In a 10-year longitudinal study, only 25% of 162 people with Parkinson’s accessed formal domestic care. Much of the burden of caring appears to be being met by informal carers. A need for greater awareness of services ( to read more about this).
  • Interesting manuscript on biorxiv looking at phase-dependent suppression of beta oscillations in people with Parkinson’s during deep brain stimulation surgery. The researchers demonstrate that in each person with Parkinsons there is a specific phase of the subthalamic activity at which consecutive pulses of local electrical stimulation can suppress the amplitude without changes to overall excitability ( to read the manuscript).

  • New research suggests that reduced levels of the neurotransmitter GABA are associated with visual hallucinations in Parkinson’s. Changes to the ventral visual stream are implicated in the genesis of visual hallucinations ( to read more about this).
  • Galvanic skin responses, as measured by SudoScan did not demonstrate significant sudomotor dysfunction in idiopathic REM Sleep Behavior Disorder (RBD), but decreases were seen in the Parkinson’s subtype associated with RBD ( to read more about this).
  • Overactive bladder is a common feature in Parkinson’s. New retrospective study found that 50% of people with PD treated with mirabegron had improved overactive bladder symptoms after 6 weeks ( to read more about this).
  • New research from New Zealand (yay!) presents differential occurrence of Parkinson’s across the major ethnic groups within the NZ population, with indigenous Māori showing the lowest incidence. Interesting: “The 2013 age‐standardized prevalence (per 100,000 population) was European, 223; Asian, 174; Pasifika, 160; Māori, 114” – in other words, the prevalence of Parkinson’s in the Māori community is almost 50% that of the Pākehā (European –  to read more about this).
  • Israeli engineers publish clinical results demonstrating breath analysis can be used to differentiate 29 recently diagnosed people with Parkinson’s from 19 control subjects, to an accuracy rate of 80% ( to read more about this).

  • An interesting case study report of PARKIN-associated Parkinson’s with no Lewy body pathology ( to read more about this).
  • Interesting case study/postmortem analysis of a person who had Parkinson’s with a R1441G mutation in the LRRK2 gene. A lack of central & peripheral nervous system alpha synuclein pathology was found (Click here to read more about this).
  • Does a clock tick slower or faster for people with Parkinson’s? Results from a synchronized tapping test suggest that recently diagnosed individuals generally tapped ahead of the tones. L-Dopa had no effect on the tapping performance ( to read more about this).
  • 694 autopsy analyses suggest that contact sports participation may increase risk of developing Lewy body conditions similar to Parkinson’s ( to read more about this).
  • An analysis of macroautophagy-related proteins were analyzed in postmortem brains from people with G2019S LRRK2-associated Parkinson’s. Lower p62 & LAMP1 protein levels were observed, compared to idiopathic PD cases ( to read more about this).
  • Interesting analysis of effect of dopamine therapy on non-motor features in late stage Parkinson’s. Spoiler alert: There is an effect – highlights “importance to optimize dopaminergic therapy in order to give the most effective” treatment ( to read more about this).
  • Interesting analysis of spatial distribution of Parkinson’s prevalence in Québec based on hydrographic regions ( to read more about this).

 

Clinical trial news

  • Australian firm Prana biotechnology has initiated Phase 1 clinical testing of their PBT434 for treatment of Parkinson’s. PBT434 has been found to prevent iron mediated neurodegeneration & alpha synuclein toxicity in multiple models of PD ( to read more about this and click here to read a previous SoPD post on this topic).

  • A 10 week randomised controlled trial of highly challenging balance training in Parkinson’s finds that training effects diminish within 6 months of cessation, implying that the program may need to be repeated regularly ( to read more about this).
  • Functional improvements in Parkinson’s following a randomised clinical trial of Yoga. Individuals in the 8-week yoga intervention group significantly reduced their fall risk ( to read more about this).
  • Voyager Therapeutics has receives FDA guidance regarding the development path for their gene therapy treatment (VY-AADC) that is being clinically trialled for Parkinson’s. Also provided clinical update for the Phase 1 posterior trajectory trial ( to read the press release and click here to read a SoPD post on this topic).

  • Finnish researchers conducted a randomised controlled trial of training working memory in Parkinson’s to test the feasibility & efficacy of home-based computerised training. Results suggest post test improvement also on untrained working memory tasks ( to read more about this).
  • Hints of possible effect in Phase II immunotherapy clinical trial for Alzhiemer’s. Biogen & Eisai announce significant effect at 18 months for BAN2401 – few details as yet. Implications for immunotherapy in Parkinson’s? (

  • Injectable daxibotulinumtoxinA – an investigational botox Type A – has been found to be well tolerated in a clinical trial & may offer prolonged efficacy in the treatment of cervical dystonia associated with Parkinson’s ( to read more about this).
  • Significantly greater improvement both in MDS‐UPDRS in a clinical trial assessing the use of multiple simultaneous microelectrode recordings for electrode placement in deep brain stimulation in Parkinson’s (vs single sequential microelectrode recordings –  to read more about this).
  • Researchers have initiated a clinical study to re-purpose ketamine – a drug currently used to treat pain and depression – to test its ability to reduce/control Ldopa induced dyskinesias in people with Parkinson’s ( to read more about this).
  • Elto Pharma (a subsidiary of Amarantus Biotech) has announced a Phase 2 clinical study of eltoprazine -5HT1A/1B partial agonist – for Ldopa-induced dyskinesias in Parkinson’s will launch in the first half of 2019 ( to read more about this).

  • A randomised, double-blind, placebo-controlled clinical trial of Zishenpingchan granules (an interesting combination of Chinese & Western medicine) for the treatment of Parkinson’s demonstrates interesting results ( to read more about this).
  • A randomised clinical trial finds that rhythmic auditory stimulation (RAS) training significantly reduced the number of falls in Parkinson’s & modified key gait parameters, such as velocity and stride length ( to read more about this).
  • New clinical trial results report that apomorphine infusion results in a clinically meaningful reduction in OFF time in people with Parkinson’s with persistent motor fluctuations (despite optimised oral or transdermal therapy –  to read more about this).

 

Other news

  • I was sorry to hear of the passing of Prof Arvid Carlsson on the 29th June. Readers may not be aware of who he was, but Prof Carlsson had a major impact on the world of Parkinson’s research. It was his discovery of the effects of dopamine on the brain that led to the later development of Levodopa as a treatment for Parkinson’s. He was awarded the Nobel prize for Physiology or Medicine in 2000 for his efforts. He certainly left an amazing legacy and he will be greatly missed.

  • Merz Neuroscience announce FDA approval of Xeomin (Botulinum toxin) for chronic sialorrhea or excessive drooling – a common symptom in conditions like Parkinson’s or amyotrophic lateral sclerosis (ALS –  to read more about this).
  • Herantis Pharmaceuticals announces the initiation of a ‘non-invasive CDNF’ development program. CDNF (or cerebral dopamine neurotrophic factor) is a protein that has been shown to be beneficial in models of Parkinson’s & is currently in clinical trials for PD ( to read the press release).

  • New research on the prevalence of Parkinson’s in North America. “We estimate the overall prevalence of PD among those aged ≥45 years to be 572 per 100,000”. 680,000 individuals in US aged ≥45 years with PD in 2010 – 930,000 in 2020 & 1,238,000 in 2030 ( to read more about this).
  • Amydis Diagnostics has been awarded a Parkinson’s research grant from Michael J Fox Foundation to explore the use of their platform technology to develop an ophthalmic test to identify patients at risk for PD (based on targeting the detection of alpha-synuclein –  to read the press release).
  • Longevity Biotech initiated clinical neuroinflammation biomarker study at the Department of Veterans Affairs to investigate immune related aspects of Parkinson’s with support from Michael J Fox Foundation. Preliminary ex-vivo therapeutic evaluations of the company’s drug candidate for PD (a peptide drug derived from Vasoactive Intestinal Peptide (VIP) called LBT-3627) will also be conducted during the course of this study ( to read the press release).

  • Johns Hopkins launched (with $36 million in financing) Neuraly Inc, a biotech firm planning to begin phase 1 clinical testing of their GLP-1 agonist NLY01 in people with Parkinson’s before the end of the year (Click here to read more about this and click here to read an SoPD post on this topic).
  • Critical Path for Parkinson’s Consortium, in partnership with Parkinsons UK, announces that the EMA has issued a positive qualification opinion on a brain imaging test/biomarker as a tool to enrich Parkinson’s clinical trials (Click here to read the press release about this).

  • Researchers are testing a drug – ITI-214 – that may be good for the head & the heart. Intra cellular therapies Inc‘s drug ITI-214 is currently being clinically trialled for Parkinson’s, but it also strengthens heart contractions in animals ( to read the press release).
  • London-based Pharmaceutical company GlaxoSmithKleine & 23andMe form a four-year collaboration to use their giant genetics database to zero in on possible targets & treatments for human conditions, such as Parkinson’s ( to read the press release).

 

Review articles/videos

  • A fantastic write up about dopamine agonists & impulse control disorders in Parkinson’s from the Prof Frank Church ( to read that post).
  • Canadian researchers provide a very interesting review on the cell loss & factors influencing the selective vulnerability of neuronal populations affected in Parkinson’s ( to read the review).
  • A nice practice-based clinical consensus provided by a multidisciplinary steering group of 8 UK-based movement disorder & Parkinson’s specialists regarding noninvasive options for ‘wearing-off’ in PD ( to read more about this).
  • Interesting review of the evidence for & against the role of Parkinson’s-associated alpha synuclein in interacting with microtubules, effecting their dynamics & (under pathogenic conditions) destabilising them, leading to disruption of axonal transport ( to read this review).
  • Numerous studies suggest people with Parkinson’s have a high risk of developing melanoma. New review discusses epidemiological studies connecting Parkinson’s & melanoma, including the possible mechanisms underlying the co-occurrence of these two conditions ( to read this review).

  • Cognitive dysfunction is a common non-motor feature of Parkinson’s that greatly impacts quality of life & that requires more study in larger groups over a longer period of time ( to read this review).
  • Genetic variation in the GBA1 gene are associated with increased risk of developing Parkinson’s, but a new review article questions if we should also be looking at the GBA2 gene ( to read more about this).
  • Interesting review of peripheral biomarkers for the early detection of Alzheimer’s & Parkinson’s. ( to read more about this).
  • Interesting review on mitochondrial abnormalities in Parkinson’s & Alzheimer’s, asking the question “can they be targeted therapeutically?” ( to read more about this).

  • Interesting review of research attempts to decelerated Parkinson’s by treatment with iron binding compounds, such as deferiprone, caffeine, niacin, nicotine & salbutamol ( to read more about this).
  • An interesting review of determinants of dopamine neuron cell loss in Parkinson’s ( to read more about this).
  • Interesting editorial in the British Medical Journal: “Full partnership with patients is essential to any modern research enterprise”…”adapting this to specific situations can be challenging” – implications for Parkinson’s? ( to read more about this).
  • Interesting review of very old onset parkinsonisms – Parkinson’s onset ≥80 years of age is rare, & displays high co-morbidity/coexistent with Alzheimer’s & cerebrovascular pathologies (Click here to read more about this).

 

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

And there it is, just some of the highlights from July 2018 – 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 August!

(Good grief, Christmas will be here before we know it!)

EDITOR’S NOTE: 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.

Published by Simon

I am the Director of Research at Cure Parkinson's. Before that I was working as a Parkinson's research scientist at the University of Cambridge where I conducted both clinical- and lab-based research on Parkinson's. I have worked in the Parkinson's research field for over 15 years - both academically and in biotech ventures. All of my views/opinions expressed here are solely my own, and may not reflect the views of my employer or associated parties.

8 thoughts on “Monthly Research Review – July 2018”

  1. Hi Simon – Kia Ora – In an earlier post you stated that you were a poor sleeper. With the amount of quality information that you put on this site, plus your day job, do you have time to sleep at al!! It is fantastic and greatly appreciated the work that you do. I know that I would never be able to find all the studies that you present. Thank you.
    A little suggestion though. With the quality of the articles that us non-research scientists have to read carefully to make sure that we understand what has been written, plus probably the majority of readers of your blog are over 60…could the font be just a little larger? Thanks again

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    1. Kia Ora Paul,
      Thanks for the comment – I do get some sleep (on Tuesdays and Thursdays). Thanks for the suggestion. I will look into increasing the font size – good idea!
      Kind regards,
      Simon

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  2. Hi Simon, as always a super comprehensive summary (the new format is working a treat by the way, very clear and easy to follow). The best stat is the one in the first paragraph – In July 2018, there were 645 research articles added…..

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    1. Hi Martin,
      Thanks for the comment – glad you liked the post. The best stat is also the worst stat for those of us trying to keep up with all the research – the pace at the moment is completely bonkers! I mean 20 new reports per day! It’s crazy.
      All extremely positive for the community though. And now on to August!
      Kind regards,
      Simon

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      2. 🙂 That’s what I figured, but in the middle of the night I thought it wiser/safer to follow the path of polite response, rather than anything less well considered.
        The issue still stands though. I am concerned that the forest is getting lost in all these trees. A better method of information dissemination is required.

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