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Cell compositions and uses thereof

A technology of composition and cell, applied in the field of composition for transplanting GABAergic neurons, capable of solving unsatisfied problems

Inactive Publication Date: 2021-02-12
THE UNIV OF SYDNEY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0007] In addition, there is provided a method for restoring or enhancing central inhibition in a subject's nervous system and for treating neurological conditions, diseases and conditions associated with impaired or insufficient activity of inhibitory interneurons or enhanced function of excitatory neurons. Cell-based therapies represent unmet need

Method used

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  • Cell compositions and uses thereof
  • Cell compositions and uses thereof
  • Cell compositions and uses thereof

Examples

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example

[0302] Experimental model and subject details

[0303] animal

[0304] Mice were obtained from ARC (Animal Resource Center, ARC) male NOD.PRKD aged 10 weeks and habituated to facilities and equipment for 2 weeks SCID.ARC . All animal experiments were blinded to treatment, and assignment to experimental groups was performed pseudo-randomly by experimenters blinded to behavioral data and health status. Mice were housed under a 12-h light-dark cycle and provided standard chow and water ad libitum at all stages. All mice were maintained in a specific pathogen-free facility and aseptic technique was used for all handling and experiments. All behaviors were performed by a single male researcher. All experiments were approved by the University of Sydney Animal Ethics Committee under Animal Ethics Protocol 938. Experimental design and documentation have been guided by the ARRIVE guidelines and in accordance with Australian National Health and Medical Research Council guidelines. ...

example 1

[0394] Example 1. Neuropathic "pain" is a conserved response to injury.

[0395] To study chronic "pain" in genetically tractable invertebrates, the inventors modeled nerve injury in adult Drosophila. In flies, surface temperatures ≥42°C trigger a strong nociceptive avoidance response or death within minutes. Taking advantage of this behavior, the inventors developed a fly hot plate evasion paradigm to study nociceptive thresholds. Wild-type (Canton S) flies showed minimal escape responses when the surface was set at 25-38°C ( figure 1 A, not shown). However, when the animals were exposed to noxious heat (42°C), uninjured flies showed a strong nociceptive escape response, where the animals exhibited approximately 3 escape responses / fly / min ( figure 1 A). Since the Drosophila TrpA family member TrpA1 (Neely et al., 2011; Zhong et al., 2012) and indolence (Neely et al., 2010; Tracey et al., 2003) are required for acute heat nociception in larval and adult flies , so the i...

example 2

[0397] Example 2. Allodynia is mediated by TrpA1 in ppk+ sensory neurons

[0398] In larvae, ppk+ sensory neurons block the animal's body and transduce acute noxious thermal responses (Zhong et al., 2010). In adult flies, the inventors observed the organization of ppk+ neurons into possible sensory structures in the legs ( figure 2 A), where ppk+ cell bodies are localized along the legs ( figure 2 B) and ppk+ neurons peripherally and send projections to the ventral nerve cord (VNC) and brain ( figure 2 C, Figure 8 C-8E). Importantly, when the inventors blocked the synaptic output of ppk+ neurons with UAS-tetanus toxin, the animals no longer exhibited allodynia after injury ( figure 2 D), while otherwise showing comparable mobility (not shown). Furthermore, while control animals exhibited a sensitive escape response to 38°C following injury, both indolent and TrpA1 mutant animals were completely resistant to this effect ( figure 2 E) And shows no sensitization even ...

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Abstract

This invention relates to compositions and methods for the transplantation of GABAergic neurons. GABAergic neurons and compositions comprising the same according to the present invention may be used as cell-based therapies for restoring or reinforcing central inhibition in the nervous system of a subject and for the treatment of neurological conditions, diseases and disorders associated with impaired or aberrant neural function. In a preferred embodiment, the transplant composition comprise of GABAergic neurons, a GFR-alpha agonist, and at least one cell death inhibitor, and that the GABAergicneurons are generated by differentiating pluripotent stem cells, multipotent stem cells, or progenitor cells.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to Australian Provisional Application No. 2018902072, filed 8 June 2018, the entire contents of which are hereby incorporated by cross-reference. [0003] The present invention relates to compositions and methods for transplanting GABAergic neurons. GABAergic neurons according to the present invention and compositions comprising the same can be used in cell-based therapies to restore or potentiate central depression in the nervous system of a subject and to treat neurological disorders associated with impaired or abnormal neurological function. Conditions, diseases and disorders. Background technique [0004] Chronic pain already has a dramatic impact on the quality of life of hundreds of millions of patients, families and caregivers worldwide, and current therapies do not adequately address pain for the majority of patients. Globally, chronic pain is estimated to cost trillions of dol...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K35/30A61P25/04A61P25/00A61P25/28A61P29/00C12N5/0793C12N5/10
CPCA61P25/02A61K35/30A61K35/545A61K38/185A61K31/4178A61K31/221C12N5/0619A61K2121/00C12N2506/45A61K2300/00A61P25/04C12N2501/13C12N2501/80A61K31/635A61K45/06A61K9/0085A61K31/497C12N2501/119C12N2501/155C12N2501/41C12N2501/415C12N2501/845
Inventor G·尼利L·凯伦J·马妮恩
Owner THE UNIV OF SYDNEY
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