Vtft isoform of a bpifb4 protein for use in neuronal diseases and injuries

A neuron and isotype technology, applied in neurological diseases, mammalian proteins, peptide/protein components, etc., can solve the problems of metabolic antioxidant disappointment, inability to enhance mitochondrial antioxidant levels, etc.

Pending Publication Date: 2020-05-01
LGV1 SRL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, metabolic antioxidants have shown disappointing results in clinical trials
[0032] A major limitation of antioxidant therapy in the treatment of neuronal disease and injury, as well as other conditions characterized by mitochondrial dysfunction, has been the inability to enhance antioxidant levels within mitochondria

Method used

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  • Vtft isoform of a bpifb4 protein for use in neuronal diseases and injuries
  • Vtft isoform of a bpifb4 protein for use in neuronal diseases and injuries
  • Vtft isoform of a bpifb4 protein for use in neuronal diseases and injuries

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Experimental program
Comparison scheme
Effect test

Embodiment approach

[0166] According to other embodiments of the present invention, there is provided:

[0167] A protein for the treatment or prevention of a disorder selected from neuronal diseases and injuries, said protein being a VTFT isoform of BPIFB4 protein or a functional fragment thereof, said disease and injury being associated with mitochondrial dysfunction and / or protein aggregation related. A polynucleotide encoding such a protein and a vector comprising such a polynucleotide are also provided.

[0168]A protein which is a VTFT isoform of BPIFB4 protein or a functional fragment thereof for the treatment or prevention of a disease selected from the group consisting of: Alzheimer's disease; Parkinson's disease; Huntington's amyotrophic lateral sclerosis; spinocerebellar ataxias (SCA), especially SCA1, SCA2, SCA3, SCA6, SCA7, SCA17; Friedrich's ataxia; Down syndrome; Wolfler Mus syndrome; mitochondrial myopathy, encephalopathy, lactic acidosis with stroke-like episodes; Chakmaledus d...

Embodiment 1-V

[0176] Effect of embodiment 1-VTFT-hBPIFB4 carrier on cell metabolism

[0177] To establish how VTFT-hBPIFB4 affects cellular metabolism, the bioenergetics profile of HEK293T cells transfected with pRK5 empty vector (EV) or pRK5VTFT-hBPIFB4 (VTFT-hBPIFB4) was measured.

[0178] Metabolic profiles were assessed in HEK293T cells 72 h after transfection with EVs or VTFT-hBPIFB4 encoding pRK5 plasmids.

[0179] Indices of mitochondrial respiratory function were calculated from the OCR profiles: basal OCR (before oligomycin addition) and ATP-related OCR (calculated as the difference between basal OCR rate and oligomycin-induced OCR rate).

[0180] Indices of glycolytic pathway activation were calculated from ECAR profiles: basal ECAR (after glucose addition) and glycolytic capacity (calculated as the difference between oligomycin-induced ECAR and 2-DG-induced ECAR).

[0181] Data are expressed as mean ± s.e.m. from 2 separate experiments. n=5 replicates per sample. A two-taile...

Embodiment 2

[0193] Example 2 - Huntington's disease model

[0194] The therapeutic potential of AAV-VTFT-hBPIFB4 was investigated in a transgenic mouse model of Huntington's disease (HD). HD is caused by the amplification of a polyglutamine channel encoded by polyCAG in the N-terminal region of huntingtin (Htt). The R6 / 2 mouse model is a transgenic mouse with a poly-CAG expansion between 115 and 150 repeats in exon 1 of the Htt gene. This is the most commonly used and best characterized model of human pathology and is characterized by progressive loss of cognitive and motor function, both at the molecular level (with similar toxic Similar to human diseases (transfer defects) all show different degrees of similarity with human diseases.

[0195] Analysis of Movement Behavior

[0196] Fine motor skills and coordination were measured using a well-validated motor test as previously described. All tests were performed during the light-dark light phase. Six to nine mice per experimental ...

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PUM

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Abstract

The invention relates inter alia to a protein which is a VTFT isoform of a BPIFB4 protein or a functional fragment thereof for use in the treatment or prophylaxis of a condition selected from neuronaldiseases and injuries, said diseases and injuries being associated with mitochondrial dysfunction and / or protein aggregation and / or ameliorated by CXCR4 activation.

Description

technical field [0001] The present invention relates to novel therapeutic uses of VTFT isoforms of bactericidal / permeability-increasing protein family B, member 4 (BPIFB4) proteins, in particular for the treatment or prevention of disorders selected from neuronal diseases and injuries, said diseases and Damage was associated with mitochondrial dysfunction and / or protein aggregation and / or ameliorated by CXCR4 activation. [0002] Background of the invention [0003] The present inventors previously reported a lifespan-associated variant of the BPIFB4 protein, one that is involved in processes important for cellular and organismal homeostasis and whose role in regulating eNOS is enhanced by the VTFT isoform A multitasking protein, the VTFT isoform is a genetic variant that was found to be associated with unusual longevity compared to the predominant INLI isoform ("wild type") and rare INFT isoforms. See Villa et al., (2015) and WO2014102343, the contents of which are incorpor...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/47
CPCC07K14/4742C07K2319/21A61P25/28A61K38/1709A61K48/00A61K38/1751C07K14/00A61K38/16C07K14/435A61K38/17C07K14/47A61P25/00A61P25/16A61P25/14
Inventor 安尼巴莱·亚历山德罗·普卡
Owner LGV1 SRL
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