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https://atuka.com/wp-content/uploads/2024/11/1730305195778-1024x576.png 1024w, https://atuka.com/wp-content/uploads/2024/11/1730305195778-768x432.png 768w" sizes="(max-width: 1280px) 100vw, 1280px" /></figure> <div class="wp-block-columns is-layout-flex wp-container-core-columns-is-layout-1 wp-block-columns-is-layout-flex"> <div class="wp-block-column is-layout-flow wp-block-column-is-layout-flow" style="flex-basis:100%"> <div class="wp-block-group has-global-padding is-layout-constrained wp-block-group-is-layout-constrained"><div class="alignleft wp-block-template-part"> <div class="wp-block-group is-layout-flow wp-block-group-is-layout-flow"> <div class="wp-block-group is-content-justification-left is-layout-flex wp-container-core-group-is-layout-3 wp-block-group-is-layout-flex"><div class="wp-block-post-date"><time datetime="2024-11-08T14:31:00+00:00"><a href="https://atuka.com/highlights-from-neuroscience-2024-advances-in-parkinsons-disease-research/">Nov 8, 2024</a></time></div> <p class="has-contrast-2-color has-text-color">—</p> <div class="taxonomy-category wp-block-post-terms"><a href="https://atuka.com/category/behind-the-science/" rel="tag">Behind the Science</a></div></div> </div> </div></div> </div> </div> <div class="wp-block-group has-global-padding is-content-justification-left is-layout-constrained wp-container-core-group-is-layout-6 wp-block-group-is-layout-constrained"><h2 style="padding-right:0;padding-left:0;margin-right:0;margin-left:0;" class="wp-block-post-title has-xx-large-font-size">Highlights from Neuroscience 2024</h2></div> <div class="entry-content wp-block-post-content has-global-padding is-layout-constrained wp-container-core-post-content-is-layout-1 wp-block-post-content-is-layout-constrained"> <p>___</p> <p id="ember4195">Earlier this month at Neuroscience 2024, the annual summit of the Society for Neuroscience, over 22,000 attendees converged in Chicago to discuss every aspect of neuroscience imaginable. Amongst those present on behalf of Atuka were <a href="https://www.linkedin.com/in/patrick-howson-8b017411/">Patrick Howson</a>, <a href="https://www.linkedin.com/in/michael-hill-080b186/">Michael Hill</a>, <a href="https://www.linkedin.com/in/donya-a-a17011206/">Donya Aref</a> , and <a href="https://www.linkedin.com/in/tom-johnston-56027521/">Tom Johnston</a>, who were there to share our own data, a new anxiety model we are developing in non-human primates, further characterization of our mouse AAV-alpha synuclein model, and a study evaluating a potential therapeutic target in biopsy samples collected from people with Parkinson’s disease and age-matched controls.</p> <p id="ember4200">Obviously, given the size of the conference, it was impossible to see everything, but some of the highlights included:</p> <h3 class="wp-block-heading" id="ember4201">Innovations by collaborators and partners</h3> <p id="ember4202">Our longtime friends at <a href="https://www.linkedin.com/company/maplight-therapeutics-inc/">MapLight Therapeutics, Inc.</a> are using cutting-edge optogenetic and transcriptomic approaches to seek novel therapies for conditions including schizophrenia and Parkinson’s disease. Another of Atuka’s collaborators, <a href="https://www.linkedin.com/in/andrew-west-a844b4301/">Andrew West</a> from Duke University, presented an impressive number of posters continuing work into interactions between LRRK2, synuclein, and Rab10 in Parkinson’s disease. Pharmacodynamic responses in these two markers were evaluated in non-human primate biofluids treated acutely or chronically with LRRK2 kinase inhibitors.</p> <p id="ember4204"><a href="https://www.abstractsonline.com/pp8/#!/20433/presentation/28346">Preliminary results</a> in Andy’s posters suggest that both serum and CSF concentrations of total LRRK2, and the ratio of pT73-Rab10 to total Rab10, are highly pharmacodynamic and rapidly diminish with LRRK2 inhibition. These studies will reveal the relationship between free drug levels and the fluid biomarkers to help establish a foundation for the successful integration of these markers into ongoing clinical trials for LRRK2-targeting therapeutics.</p> <p id="ember4205">The poster presented by <a href="https://www.linkedin.com/in/na-ra-lee-49837575/">Na-Ra Lee</a> of <a href="https://www.linkedin.com/company/cjbioscience/">CJ Bioscience</a> investigated CJRB-302, a live biotherapeutic derived from healthy human gut microbiota, for its potential as a treatment for PD. Atuka had previously worked on this live biotherapeutic with 4D Pharma before CJ Bioscience purchased 4D Pharma’s intellectual property in 2023. These data, that confirmed and extended those produced by Atuka, show CJRB-302 reduced inflammation and cytotoxicity in cell models, improved neuronal markers, and alleviated motor deficits in a mouse model of PD.</p> <h3 class="wp-block-heading" id="ember4207">Potential therapeutic developments in Parkinson’s disease</h3> <p id="ember4208">It was valuable to hear about the preclinical development of NTX101, a nitrated alpha synuclein antibody, from <a href="https://www.linkedin.com/in/arun-kashyap-b92973a/">Arun Kashyap</a> and colleagues from <a href="https://www.linkedin.com/company/nitrase-therapeutics/">Nitrase Therapeutics</a>, in collaboration with <a href="https://www.linkedin.com/company/dzne/">German Center for Neurodegenerative Diseases (DZNE)</a> in Bonn. Nitrated alpha synuclein is known to accelerate the rate of fibril formation of unmodified alpha synuclein. Therefore, by targeting nitrated synuclein the aggregation and spread of alpha synuclein can be prevented, and this was demonstrated in two models of PD. The compound is now moving into IND-enabling studies, and we await further development with interest.</p> <p id="ember4210">We were pleased to see efforts to understand and derive novel therapeutic approaches for symptomatic relief and motor-complications in PD from <a href="https://www.linkedin.com/in/chris-bishop-1741175/">Chris Bishop</a>’s group at Binghampton University. Their group also further explored better research tools to facilitate and automate assessment of certain time-consuming and human rater-reliant rodent model behavioural endpoints such as abnormal involuntary movements.</p> <h3 class="wp-block-heading" id="ember4212">Advancing our understanding of the disease</h3> <p id="ember4213">It was interesting to see the continued use of technologies that will drive the next generation of models in Parkinson’s disease. <a href="https://www.abstractsonline.com/pp8/#!/20433/presentation/28373">In one poster by CINAC’s N. Esteban Garcia and others</a>, brain penetrance of AAV9-PHPeB in NHPs was greatly enhanced following disruption of the BBB using focused ultrasound, whereas <a href="https://www.abstractsonline.com/pp8/#!/20433/presentation/29742">in another poster from Matthew Jennings from Columbia University,</a> the same viral vector, expressing human mutated A53T-alpha synuclein, was able to produce widespread brain synuclein pathology when administered via intravenous injection. If these approaches are combined then it may be possible to produce an alpha-synuclein driven, NHP model of PD without the need for invasive, MRI-guided, brain surgery.</p> <p id="ember4214">On the topic of techniques for spatio-temporal characterization of the neurodegenerative process, we connected with the team at <a href="https://www.linkedin.com/company/gubra/">Gubra</a>, who presented a poster on the 3D quantification of alpha-synuclein spread in a mouse model of Parkinson’s disease. The spatiotemporal pattern of phosphorylated alpha-synuclein they observed replicates what we have seen in our own work with this model. We are also excited to explore the application of 3D imaging and quantification further in collaboration with Gubra.</p> <p id="ember4215">There was solid interest in the role of the immune system in Parkinson’s disease, with several posters (notably <a href="https://www.abstractsonline.com/pp8/#!/20433/presentation/29747">from Alice Calderoni and collaborators at the San Raffaele Scientific Institute in Italy</a> and <a href="https://www.abstractsonline.com/pp8/#!/20433/presentation/12559">Ewald Auer and his group from Austria’s Scantox</a>) demonstrating an increase in peripherally recruited T-cells, in various animal models of PD. This work supports our own research and replicates clinical findings. Interestingly, <a href="https://www.abstractsonline.com/pp8/#!/20433/presentation/28288">data presented by Huixin Xu from Harvard Medical School</a> showed that the choroid plexus, a highly vascularised epithelial tissue responsible for producing CSF, was an important site for peripheral t-cell infiltration into the CNS in animal models of neurodegenerative disorders. It will be interesting to see if targeting the choroid plexus becomes a therapeutic target in PD.</p> <p id="ember4216">In a particularly enlightening lecture, Dr. <a href="https://www.linkedin.com/in/bart-de-strooper-8bb1069/">Bart De Strooper</a> highlighted the complex interplay of microglia, astrocytes, and neurons in neurodegenerative diseases, and specifically within areas of protein aggregation, such as the amyloid plaque niche. He discussed the diverse roles immune cells can play to either drive, attenuate, or halt neurodegeneration at different disease stages. For example, microglia seem to have a generic response to amyloid plaque formation, regardless of brain region; while astrocytes have a much more heterogeneous response to plaques, that is brain-region-dependent. It was clear that improving our methods for understanding temporal and spatial changes in the neurodegenerative process is critical.</p> <hr class="wp-block-separator has-alpha-channel-opacity"/> <p id="ember4218">Neuroscience 2024 was a powerful reminder of the momentum within the neuroscience community and the progress we’re collectively making in neurodegenerative disease research. From innovative models to new therapeutic targets, it’s clear that collaboration and advancing technologies are central to moving the field forward. We are proud of the contributions made by the Atuka team and our collaborators, and we’re inspired by the shared commitment we saw in Chicago to improving outcomes for those affected by Parkinson’s and other neurological conditions. 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