[GUEST ACCESS MODE: Data is scrambled or limited to provide examples. Make requests using your API key to unlock full data. Check https://lunarcrush.ai/auth for authentication information.]  mike [@mike98572986](/creator/twitter/mike98572986) on x XXX followers Created: 2025-07-16 17:11:29 UTC $clpt Roche/Spark therapeutics study, new research paper using clearpoint Overall, the findings of this study will help guide the selection of the best retrograde AAV capsid for treatment of specific brain diseases. Vector was delivered into the bilateral putamen using intra-MRI guidance and the SmartFlow® Neuro Cannula ClearPoint Neuro; Solano Beach, CA Recent advances in neuroimaging techniques have helped delineate the structural and functional connectivity of the human brain and indicated that neurodegenerative diseases tend to target specific brain networks, damaging their function.rAAV gene therapy has shown significant promise in treating various genetic and acquired CNS disorders, for most of which there is currently no cure or effective treatment. One of the most critical challenges in CNS gene therapy development is the precise and efficient targeted delivery of rAAVs to disease-affected brain structures and associated dysfunctional neural networks. Direct IPa delivery into the brain can be used to take advantage of the existing axonal tracts for distant widespread transgene expression in projection neurons of target brain regions. However, many natural AAV serotypes do not readily enter axon terminals and therefore have a limited capacity for retrograde transport. Hence, there is a strong need for novel AAV variants with robust retrograde transduction properties in diverse neuronal populations in the brain. We leveraged recent advances in neurosurgical approaches for IPa gene transfer, including convection-enhanced delivery (CED) of MRI contrast-spiked infusate using the reflux-resistant SmartFlow® Neuro Cannula, to monitor and verify AAV vector infusion and target coverage in real time We report here capsid variants with enhanced retrograde transport and expression compared to the parental AAV2 capsid. These properties make them potentially useful for disease indications in which broader brain coverage is desirable beyond the injection site Moreover, the retrograde axonal transport property of AAVs, which is serotype-dependent, can be harnessed for therapeutic purposes to transduce functionally connected brain regions distal to the IPa injection site. In many CNS disorders, disease-specific pathologies extend beyond the initially affected brain region, impacting distributed circuits and networks. Thus, it is desirable to engineer AAV capsids with both high retrograde transport efficiency and specific cell tropism, as vehicles to deliver AAVs throughout the brain and to disease-affected cell types. In this study, we evaluated a library of XX barcoded AAV2 variants (i.e., MNM001-MNM025) in X adult cynomolgus monkeys following bilateral IPa administration into the putamen. These XX AAV variants were compared with the parental AAV2 capsid and benchmark capsids AAV2-retro,13 AAV9, and AAV9-retro The MNM021 variant also emerged as the capsid both widely distributed throughout the brain and enriched at the injection site, making it potentially amenable to use in gene therapy applications where it is beneficial to treat both the disease-vulnerable brain region and the associated dysfunctional networks. This approach could enhance the therapeutic benefits in human patients afflicted with Huntington’s disease, Parkinson’s disease, Alzheimer’s disease, or other CNS diseases that affect multiple brain regions and/or neural networks. Specifically with respect to Huntington’s disease, a single injection into the putamen, or into both caudate and putamen, could simultaneously treat the disease’s core pathology, which involves progressive degeneration of the basal ganglia, and the cortico-striatal network, characterized by widespread projections from numerous areas of the cortex to the caudate and putamen. To this end, utilizing retrograde AAVs for single-injection treatments would be more feasible and efficient than administering multiple injections into different cortical areas XXX engagements  **Related Topics** [$clpt](/topic/$clpt) [Post Link](https://x.com/mike98572986/status/1945531747992834445)
[GUEST ACCESS MODE: Data is scrambled or limited to provide examples. Make requests using your API key to unlock full data. Check https://lunarcrush.ai/auth for authentication information.]
mike @mike98572986 on x XXX followers
Created: 2025-07-16 17:11:29 UTC
$clpt Roche/Spark therapeutics study, new research paper using clearpoint
Overall, the findings of this study will help guide the selection of the best retrograde AAV capsid for treatment of specific brain diseases.
Vector was delivered into the bilateral putamen using intra-MRI guidance and the SmartFlow® Neuro Cannula ClearPoint Neuro; Solano Beach, CA Recent advances in neuroimaging techniques have helped delineate the structural and functional connectivity of the human brain and indicated that neurodegenerative diseases tend to target specific brain networks, damaging their function.rAAV gene therapy has shown significant promise in treating various genetic and acquired CNS disorders, for most of which there is currently no cure or effective treatment. One of the most critical challenges in CNS gene therapy development is the precise and efficient targeted delivery of rAAVs to disease-affected brain structures and associated dysfunctional neural networks. Direct IPa delivery into the brain can be used to take advantage of the existing axonal tracts for distant widespread transgene expression in projection neurons of target brain regions. However, many natural AAV serotypes do not readily enter axon terminals and therefore have a limited capacity for retrograde transport. Hence, there is a strong need for novel AAV variants with robust retrograde transduction properties in diverse neuronal populations in the brain.
We leveraged recent advances in neurosurgical approaches for IPa gene transfer, including convection-enhanced delivery (CED) of MRI contrast-spiked infusate using the reflux-resistant SmartFlow® Neuro Cannula, to monitor and verify AAV vector infusion and target coverage in real time
We report here capsid variants with enhanced retrograde transport and expression compared to the parental AAV2 capsid. These properties make them potentially useful for disease indications in which broader brain coverage is desirable beyond the injection site
Moreover, the retrograde axonal transport property of AAVs, which is serotype-dependent, can be harnessed for therapeutic purposes to transduce functionally connected brain regions distal to the IPa injection site. In many CNS disorders, disease-specific pathologies extend beyond the initially affected brain region, impacting distributed circuits and networks. Thus, it is desirable to engineer AAV capsids with both high retrograde transport efficiency and specific cell tropism, as vehicles to deliver AAVs throughout the brain and to disease-affected cell types.
In this study, we evaluated a library of XX barcoded AAV2 variants (i.e., MNM001-MNM025) in X adult cynomolgus monkeys following bilateral IPa administration into the putamen. These XX AAV variants were compared with the parental AAV2 capsid and benchmark capsids AAV2-retro,13 AAV9, and AAV9-retro
The MNM021 variant also emerged as the capsid both widely distributed throughout the brain and enriched at the injection site, making it potentially amenable to use in gene therapy applications where it is beneficial to treat both the disease-vulnerable brain region and the associated dysfunctional networks. This approach could enhance the therapeutic benefits in human patients afflicted with Huntington’s disease, Parkinson’s disease, Alzheimer’s disease, or other CNS diseases that affect multiple brain regions and/or neural networks. Specifically with respect to Huntington’s disease, a single injection into the putamen, or into both caudate and putamen, could simultaneously treat the disease’s core pathology, which involves progressive degeneration of the basal ganglia, and the cortico-striatal network, characterized by widespread projections from numerous areas of the cortex to the caudate and putamen. To this end, utilizing retrograde AAVs for single-injection treatments would be more feasible and efficient than administering multiple injections into different cortical areas
XXX engagements
Related Topics $clpt