Today’s (experimental) post provides something new – an overview of some of the major bits of Parkinson’s-related research that were made available in January 2018.
In January of 2018, the world was rocked by news that New Zealand had become the 11th country in the world to put a rocket into orbit (no really, I’m serious. Not kidding here – Click here to read more). Firmly cementing their place in the rankings of world superpowers. In addition, they became only the second country to have a prime minister get pregnant during their term in office (in this case just 3 months into her term in office – Click here to read more about this).
In major research news, NASA and NOAA announced that 2017 was the hottest year on record globally (without an El Niño), and among the top three hottest years overall (Click here for more on this), and scientists in China reported in the journal Cell that they had created the first monkey clones, named Zhong Zhong and Hua Hua (Click here for that news)
Zhong Zhong the cute little clone. Source: BBC
More importantly, in the world of Parkinson’s research, scientists reported that:
Mitochondrial targeted HSP90 inhibitor, Gamitrinib-triphenylphosphonium – an anti-cancer agent – induces Parkinson’s-associated PINK1/Parkin-dependent waste disposal of unhealthy mitochondria (mitophagy) (Click here to read the research report).
Mutations in glycosphingolipid (GSL)-degrading glucocerebrosidase (GBA) gene is a risk factor for Parkinson’s. Reducing GSLs in PD patient neurons (with & without GBA mutations) in culture reduced pathology & restored normal alpha-synuclein function (Click here to read the report and click here to read the SoPD post on the topic).
Subthalamic nucleus deep brain stimulation may have the potential for improving posture in people with advanced Parkinson’s (Click here to read this research report and click here for the explanation ).
Deep brain stimulation of the subthalamic nucleus. Source: Health-innovations
Accumulation of PARIS (a protein which interacts with several Parkinson’s associated proteins) might distort the balance of glucose metabolism. An inhibitor of PARIS might be a useful thing… I’m just saying (Click here to read the research report). We have previously discussed PARIS on the website regarding other research on this topic (Click here to see that post).
Prion-like propagation of the toxic form of Parkinson’s-associated protein alpha synuclein is regulated by the FcγRIIB-SHP-1/2 signalling pathway in neurons (Click here to read the research report).
A bioinformatics approach for repositioning drugs for Parkinson’s suggests that #1 Estradiol (a steroidal estrogen), #2 Resveratrol (a stilbenoid), followed by three retinoids. Food for thought, but please discuss with your doctor before changing your diet or treatment regime (Click here to see this research). There is also a post on the SoPD website regarding Resveratrol (Click here for that post).
New clinical study found that 108 people with Parkinson’s had significantly lower blood levels of caffeine and 9 of 11 byproducts of caffeine in their blood than 31 people without Parkinson’s… even if they consumed the same amount of caffeine! Is caffeine in the blood a new biomarker for Parkinson’s? (Click here to see more about this research, and click here for a previous SoPD post on Caffeine).
Caffeine. Source: Medium
High hopes for CRISPR-Cas9 gene editing technology suffered a set back as researcher found that more than 65 percent of the people tested carried antibodies for the two most commonly used Cas9 proteins. Immunity could mean that CRISPR-based treatments won’t work in these folks. This immunity probably results from Cas9-containing bacteria infecting our bodies and our immune system responding (Click here to read the research pre-print manuscript).
Chinese researchers find that Parkinson’s-associated protein synaptotagmin-11 interacts with another PD-associated protein: PARKIN. They also found that this interaction plays a critical role in the PARKIN-linked neurotoxicity. PARKIN deficiency shown to cause synaptotagmin-11 accumulation and subsequent neurodegeneration. Reducing synaptotagmin-11 reverses this neurotoxicity. Novel therapeutic target? (Click here to read more on this).
Biotech company Axovant Sciences announced negative results for Intepirdine (selective 5-HT₆ receptor antagonist) in Phase IIb HEADWAY & pilot Phase II Gait and Balance Studies for people with Lewy bodies dementia (Click here to read the press release).
Source: Axovant Sciences
LRRK2 inhibitor, PFE-360, being developed by Lundbeck for Parkinson’s causes morphological changes in the kidneys of mice after 2 weeks of treatment, BUT this is partially reversible after 30 day treatment-free period (Click here to read the research report and click here to read a SoPD post about LRRK2 inhibitors).
The results of a longitudinal study of 544 subjects demonstrates a slower decline in motor features of Parkinson’s among those with LRRK2 G2019S genetic variant (Click here to read more on this).
More data was published suggesting that GBA deficiency (due to L444P GBA genetic variant) and the accompanying accumulation of alpha synuclein protein renders dopamine neurons more susceptible to neurotoxic model of Parkinson’s (Click here to read more about this).
Smell test results suggest that differential discriminatory power of individual items is NOT conserved across independent Parkinson’s cohorts, arguing against selective hyposmia in Parkinson’s (Click here to find out more about this).
Further evidence that maintaining GBA activity and reducing glycosphingolipids are important in reducing the misfolding and aggregation of alpha synclein protein in Parkinson’s (Click here to read more about this).
Transcranial ultrasound indicates that hyper echogenicity of substantia nigra (a region of the brain involved in Parkinson’s) is related to dysfunction of iron metabolism. It occurs at more advanced stages of the condition, with more severer motor symptoms (Click here to find out more about this).
The presence of shared LRRK2 genetic variants in both Crohn’s Disease and Parkinson’s provides insight into underlying mechanisms and potential treatments (Click here to see the research report).
Two distinct populations of glutamatergic excitatory neurons in the midbrain control speed & gait selection (Click here to read more about this).
New brain imaging research suggests that the degeneration observed in Parkinson’s may originate in subcortical regions and spreads along neural networks to the overlying cerebral cortex (Click here to read more on this).
Lack of Parkinson’s-associated PINK1 alters the response of glial cells (supportive cells) in the brain and enhances inflammation-induced neuronal cell death (Click here to read the research report).
The first in vivo evidence that Parkinson’s associated PINK1 is detectable at basal levels. Analysis of endogenous levels suggest that loss of PINK1 does not influence basal mitophagy (Click here to read the research report). This result was verified a few days later by another lab (Click here to read the preprint manuscript).
Smoking to known to reduce one’s risk of developing Parkinson’s, but this inverse association between smoking and Parkinson’s is less pronounced in people with genetic variations in both RXRA-rs4240705 and SLC17A6-rs1900586 (Click here to read more about this).
Analysis of gut bacteria that markedly increased dopamine neuron cell loss in mice suggest a role for ‘proteus mirabilis’ in the pathogenesis of Parkinson’s (Click here to find out more about this).
Deep brain stimulation of the subthalamic nucleus represents a one method of alleviating troublesome symptoms in Parkinson’s. Researchers in the Netherlands have analysed 65 cases to identify the ‘hotspot’ for placing electrodes (Click here to read more about this).
Scientists discovered that two key cellular structures, mitochondria & lysosomes, come into direct contact with each other in the cell to regulate their respective functions – major implications for Parkinson’s (Click here to find out more about this).
Meta-analysis review of data points towards a Parkinson’s personality – apparently novelty seeking and extraversion are inversely associated with PD (Click here to read more about this study).
Personality. Source: Moneypenny
Researchers found that postmortem Parkinson’s brain samples display increased astrocytic senescence. They also reported that cultured human astrocytes exposed to paraquat become senescent. And they found that clearance of senescent cells mitigates cell loss in a mouse model of PD (Click here to read the research report).
Parkinson’s UK announces it is funding final preclinical studies of NLX-112, a novel serotonin 5-HT1A receptor agonist for the treatment of L-DOPA-induced dyskinesia in Parkinson’s. If found to be effective on dyskinesias preclinically, this drug could progress directly to phase II clinical trials as it has been phase I tested already (Click here to read the press release).
Experimental Parkinson’s treatment Ambroxol is a GCase chaperone, but researchers have found that it also acts on other pathways, such as mitochondria, lysosomal biogenesis, and the secretory pathway (Click here to read the research report).
Ambroxol. Source: Skinflint
Voyager Therapeutics announced FDA clearance to begin dosing participants for their pivotal Phase 2-3 clinical trial of VY-AADC for advanced Parkinson’s. This is a gene therapy approach for PD (Click here to read the press release).
Green tea compound (-)-Epigallocatechin-3-gallate (EGCG) has neuroprotective effects in a model of Parkinson’s (MPTP) and it may exert this effect through modulating peripheral immune response (Click here to find out more about this).
Reducing striatal glutamate signalling may improve L-dopa treatment. Locally applied AMPAR or NMDAR antagonist reduce glutamate signalling which stabilises dopamine-induced activity increases and decreases in a primate model of Parkinson’s (Click here to read the research report).
A randomised, double-blind phase II study of Zonisamide (adjunctive to levodopa) improved Parkinson’s features in people with dementia with Lewy bodies without worsening cognitive function or psychiatric symptoms (Click here to read more about the results of this clinical trial).
Removal of prolyl oligopeptidase (or PREP) reduces Parkinson’s-associated alpha synuclein toxicity in cell and mouse base models of PD. Increasing levels of PREP enhances alpha synuclein toxicity. A very interesting therapeutic target (Click here to find out more).
Further evidence that there is an impairment in vocal motor control in Parkinson’s. The findings of a new study indicate that there may be an impairment in the adaptive control of voice in PD (Click here to read the research report).
A 3-month double-blind, randomised sham-controlled study of a repetitive deep transcranial magnetic stimulation on Parkinson’s fails to demonstrate an advantage for real treatment over sham treatment (Click here to find the research report).
Deep transcranial magnetic stimulation. Source: Wikipedia
By reducing levels of mitochondria‐localized protein ‘p13‘, researchers made mice resistance to toxin‐induced motor deficits & to the loss of dopaminergic neurons in the substantia nigra. New target for Parkinson’s? (Click here to find out more).
Miniaturized neural drug delivery system (or MINDS) are cannulas (made up of several tubes, each approx. 30 micrometers in diameter), that can be implanted in the brain and can deliver different types of medications. Implications for Parkinson’s?
Interesting possibilities for this: – multiple drugs could be administered (or tested: think adaptive clinical trials) – no blood brain barrier issues – targeted to specific brain structures – limited off-target peripheral side effects. Verdict: Very cool! (Click here to find out more).
Icariin, a single active component extracted from the Herba Epimedii, reduces dopaminergic neuronal loss & microglia-mediated inflammation in models of Parkinson’s (Click here to read the research report).
Blood serum from 73 people with Parkinson’s – divided into groups with early PD, late PD with dyskinesia & late PD without dyskinesia – demonstrates significant differences in free amino acid profiles. Interestingly they “observed some significant differences amongst the groups with respect to concentrations of alanine, arginine, phenylalanine & threonine, although no significant differences were observed between patients with advanced PD with & without dyskinesia” (Click here to read the research report).
A UK-based study confirms the influence of the Parkinson’s-associated GBA mutations on the age of onset, disease severity & motor features in PD. Cognition did not differ between GBA mutation carriers and non-carriers at baseline (Click here to read more about this work).
Pisa Syndrome (PS) occurs when the trunk of the body leans to one side – a common feature in Parkinson’s. New research suggests verticality misperception (miscalculation of one’s vertical position to the horizon) is a potent risk factor for PS (Click here to read more about this).
The US National Institute of Health (NIH) Accelerating Medicines Partnership for Parkinson’s (AMP PD) has been announced. The NIH is teaming with the government, biopharmaceutical, life science and non-profit organisations to overcome obstacles for advancing promising treatments for Parkinson’s (Click here to read the press release).
This post has been a real experiment.
These were the main Parkinson’s-related research highlights for the month of January 2018. Much of the material used here was collected from the SoPD Twitter feed (and there is a lot more posted there each day). I’m not sure I like the shopping list format, so I might have a play with it before the February’s review.
I have tried to incorporate readers’ request of having a label to indicate what sort of research each piece of news is related to (Novel drug target, clinical study, etc). I wanted to keep those labels relatively generic, but I’m not really sure I like the current style. I’ll go away and do some more experimenting with it.
For now, there is hopefully something of interest in the list above for everyone. Any feedback would be greatly appreciated.