Method for vector delivery

a vector and brain technology, applied in the direction of viruses/bacteriophages, biocide, drug compositions, etc., can solve the problems of increased bleeding risk and other surgical complications, and achieve the effect of a larger volume of vector spread within the brain

Inactive Publication Date: 2011-12-01
OXFORD BIOMEDICA (UK) LTD
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0015]The present inventors have surprisingly found that despite the size of lentiviral vectors relative to the extracellular space, it is possible to modify the multiple-tract discontinuous delivery method described for ProSavin®, increase the volume delivered per tract and the flow rate of infusion for lentiviral vectors which in turn results in a greater volume of vector spread within the brain.
[0016]Using a lentiviral vector based on the equine infectious anaemia virus (EIAV), expressing the reporter gene β-galactosidase (EIAV-LacZ), they have shown that a single continuous infusion of this genetically modified lentiviral vector distributes effectively within the putamen of cynomolgus macaques. Although vector spread in the rostro-caudal axis of the putamen was marginally less than using the previously described multiple 5 needle tract approach to manually spread out the vector distribution, vector distribution in the medio-lateral and dorso-ventral axes with the continuous single infusion paradigm was better than the 5-tract multiple deposit approach. Moreover the total volume of vector distribution in the brain was almost 2-fold greater with a single continuous infusion compared with the five-tract multiple deposit method.

Problems solved by technology

Such an approach requires complex pre-surgical planning to determine the positioning of the cannula tracts and time-consuming surgery, with an increased risk of bleeding and other surgical complications associated with the use of multiple cannula tracts to introduce the vector.

Method used

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Examples

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Effect test

example 1

Comparing Distribution of a Lentiviral Vector in the Putamen Following a) Conventional Delivery and b) Delivery Using a Single Site and a High Flow-Rate

[0138]Administration of EIAV-LacZ vector suspension using the previously described technique (50 ∞L total volume vector administered to the putamen through 5 needle tracts using a Hamilton syringe and 23-gauge needle, each delivering 10 μL per tract (via three deposits) provided a moderate spread of vector in the dorso-ventral axis of the putamen that reached between 40 and 50% the depth of this brain structure (FIG. 1).

[0139]Spread of vector in the medio-lateral axis was very much less than with the dorso-ventral axis, with the vector only spreading around 1-2 mm at the greatest point. However, due to the positioning of the five needle tracts along the axis of the putamen, spread of vector along the rostro-caudal axis was around 7.8 mm in both of the two hemispheres that were administered vector by this paradigm.

[0140]In contrast, u...

example 2

Comparing Efficacy of a Lentiviral Vector for Parkinson's Disease Following Administration to the Motor Putamen of Parkinson's Disease Patients Using a) Conventional Delivery and b) Delivery Using a Reduced Number of Injection Sites with a Narrower Gauge Device and a High Flow-Rate

[0156]A phase I / II clinical trial is ongoing to evaluate the safety and efficacy of a lentiviral vector based treatment for Parkinson's disease, called ProSavin®. ProSavin® is an EIAV lentiviral vector that contains three genes which encode for enzymes in the dopamine biosynthesis pathway. As part of the trial the therapeutic potential of ProSavin® to correct symptoms of Parkinson's disease was evaluated using 1) the conventional method of administration and 2) a continuous method of infusion. The conventional method involved injection of a total volume of 125 μL of vector administered to each putamen through 5 needle tracts using a Hamilton syringe and 23-gauge needle and an administration rate of 1 μL / mi...

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Abstract

Provided is a lentiviral vector for delivery to the brain for use in treating a neurological condition, wherein the lentiviral vector is delivered directly to the brain by delivering the lentiviral vector via six or fewer tracts per hemisphere, at a single deposit point per tract.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application claims the benefit of priority to Great Britain applications 1009052.0, filed on May 28, 2010; 1100502.2, filed on Jan. 12, 2011; and 1107184.2, filed on Apr. 28, 2011. The foregoing applications are hereby incorporated by reference in their entireties.FIELD OF THE INVENTION[0002]The present invention relates to a lentiviral vector for delivery to the brain for use in treating a neurological condition. The lentiviral vector is delivered directly to the brain by continuous infusion using a narrow bore delivery device with a reduced number of deposit points compared to previous methods.BACKGROUND TO THE INVENTION[0003]Virus-based approaches are known to treat various neurological diseases, through the introduction of therapeutic genes to transduce neuronal and / or support cells. For example, a multicistronic lentiviral vector product, ProSavin®, has been developed to treat Parkinson's disease. ProSavin® mediates intrastriata...

Claims

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Application Information

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IPC IPC(8): A61K35/76A61P25/00C12N15/63
CPCA61K48/0075A61K48/0083A61K31/711C12N2740/15043C12N15/86A61P25/00A61P25/04A61P25/06A61P25/08A61P25/14A61P25/16A61P25/18A61P25/28A61K48/005A61M5/178
Inventor WIDDOWSON, PETERRALPH, SCOTTMITROPHANOUS, KYRIACOS A.
Owner OXFORD BIOMEDICA (UK) LTD
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