Development of a novel anti-inflammatory nanoparticle for the treatment of Acute Lung Injury
Lead Research Organisation:
Queen's University Belfast
Department Name: Sch of Pharmacy
Abstract
Acute lung injury is a life threatening and incapacitating condition that affects 20% of all critically ill patients in intensive care. Around 30-50% of these sufferers will die from the condition and many survivors can have serious reductions in the quality of the life with chronic lung problems. This not only has a major effect on the patients themselves, but is also a serious resource allocation problem for the NHS as an ICU bed costs in excess of £1800 per day. There is no effective treatments for this condition at this time and therefore new medicines are urgently needed that can deal and stabilise the condition. ALI is characterised by a vicious cycle of inflammation in the lung that leads to inappropriate infiltration of immune cells to the lung. We have developed a potential treatment for this condition that may have the ability to be nasally delivered to patients in intensive care that has potent anti-inflammatory effects. This treatment is a nano-sized formulation that binds specifically to immunosuppressive receptors found on the surface of immune cells such as macrophages, resulting in significant reduction of the production of inflammatory signaling molecules called cytokines.
Therefore in this proposal we aim to bring this treatment closer to clinical development by evaluating its effectiveness in a range of preclinical models of ALI. This work will inform us on its effectiveness, side effects and formulation and dosing of the therapeutic required to obtain a significant effect.
Therefore in this proposal we aim to bring this treatment closer to clinical development by evaluating its effectiveness in a range of preclinical models of ALI. This work will inform us on its effectiveness, side effects and formulation and dosing of the therapeutic required to obtain a significant effect.
Technical Summary
Acute Lung Injury (ALI) is a serious condition associated with significant morbidity, mortality and healthcare resource utilisation, for which no effective pharmacologic treatment is available. ALI is caused by the uncontrolled activation of immune cells, resulting in an unregulated cycle of inflammation that leads to damage to the alveolar epithelial-endothelial barrier, leading to acute respiratory failure and the need for mechanical ventilation. This is therefore an area of clear unmet clinical need for effective anti-inflammatory therapies.
We have developed a novel nanoparticle which has potent anti-inflammatory effects. Here we will investigate its application in ALI by examining effects in two clinically relevant murine models of ALI (intratracheal LPS and cecal ligation and puncture), ex vivo patient and volunteer alveolar macrophages and a human ex vivo lung perfusion model. This project will provide data on physiological outcomes and toxicity upon administration with our nanoparticle to determine if further development into preclinical trials is warranted.
We have developed a novel nanoparticle which has potent anti-inflammatory effects. Here we will investigate its application in ALI by examining effects in two clinically relevant murine models of ALI (intratracheal LPS and cecal ligation and puncture), ex vivo patient and volunteer alveolar macrophages and a human ex vivo lung perfusion model. This project will provide data on physiological outcomes and toxicity upon administration with our nanoparticle to determine if further development into preclinical trials is warranted.
Planned Impact
The primary goal of this research in terms of impact is that it will significantly help the outcomes to patients in intensive care that present with ALI. This will therefore no only impact them, but carers and also then resource allocation within the health service of the UK (and internationally).
In addition to this condition, the anti-inflammatory effects of the modality make it amenable to the treatment of other conditions underpinned by inappropriate inflammation, both in the lung and in other parts of the body. With this in mind, this research is likely to impact other researchers both academically and industrially in development of follow-on therapeutics and biomaterials that can exploit these effects. Therefore it is tangible that if successful, this project could lead on to the development of other daughter therapeutics that could not only help patients suffering other inflammatory diseases, but also generate new R & D jobs and revenue for the UK.
In addition to this condition, the anti-inflammatory effects of the modality make it amenable to the treatment of other conditions underpinned by inappropriate inflammation, both in the lung and in other parts of the body. With this in mind, this research is likely to impact other researchers both academically and industrially in development of follow-on therapeutics and biomaterials that can exploit these effects. Therefore it is tangible that if successful, this project could lead on to the development of other daughter therapeutics that could not only help patients suffering other inflammatory diseases, but also generate new R & D jobs and revenue for the UK.
Publications
Spence S
(2015)
Targeting Siglecs with a sialic acid-decorated nanoparticle abrogates inflammation.
in Science translational medicine
Description | Royal Society Industrial Fellowship |
Amount | £90,000 (GBP) |
Organisation | The Royal Society |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 07/2012 |
End | 06/2015 |
Title | EVLP model |
Description | Human ex-vivo lung perfusion model of ARDS |
Type Of Material | Model of mechanisms or symptoms - human |
Provided To Others? | No |
Impact | Informed the design of subsequent clinical trials |
Description | Aviceda Therapeutics |
Organisation | Aviceda Therapeutics |
Country | United States |
Sector | Private |
PI Contribution | Aviceda have licenced the technology and IP portfolio |
Collaborator Contribution | We developed the technology that Aviceda will develop drug entities from |
Impact | Still underway |
Start Year | 2019 |
Description | Palleon Inc |
Organisation | Palleon Pharmaceuticals Inc |
Country | United States |
Sector | Private |
PI Contribution | Development of therapeutic strategies and evaluation of nanoparticle developed in this grant |
Collaborator Contribution | PAlleon have entered into official collaboration with the university and also taken an option on the nanoparticle technology developed |
Impact | Income for the university and payment for research undertaken by the university |
Start Year | 2017 |
Title | MODULATOR |
Description | There is provided a method for suppressing a pro-inflammatory immune response in a cell, comprising providing to a cell sialic acid or analogs thereof, wherein the sialic acid or analogs are presented by a substrate such that a pro-inflammatory immune response in a cell is suppressed or an anti-inflammatory immune response is increased in a cell. Further, there is provided a method of treatment of inflammatory disease in a subject in need thereof. There is also provided a drug delivery device and a biomaterial which can modulate the inflammatory response in a subject. |
IP Reference | WO2011073685 |
Protection | Patent application published |
Year Protection Granted | 2011 |
Licensed | No |
Impact | Demonstrated efficacy now in models of sepsis and acute respiratory distress syndrome |
Company Name | Avicedarx Inc |
Description | Development of new glycobiology inspired therapeutics for the treatment of a range of pathologies |
Year Established | 2019 |
Impact | Initial fund raising activities |
Website | http://www.avicedarx.com |
Description | Debating Matters, Northern Ireland |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | Yes |
Type Of Presentation | Workshop Facilitator |
Geographic Reach | Regional |
Primary Audience | Schools |
Results and Impact | Acted as judge for the session of three schhools - approx 20 pupils and teachers Have been asked to take part in a RCUK-led schools teacher training event |
Year(s) Of Engagement Activity | 2013 |
URL | http://www.debatingmatters.com/events/qr/northern_ireland_south_2013_14/ |
Description | ERS Talk |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Type Of Presentation | Keynote/Invited Speaker |
Geographic Reach | International |
Primary Audience | Participants in your research and patient groups |
Results and Impact | Invited speaker at the European Respiratory Society Meeting special section on nanotechnology. "Development of a novel nanomedicine for the treatment of Acute Lung Injury' speaker - Chris Scott; Spet 2013, Barcelona Potential industrial collaborator has come forward and initial talks on the technology have now been undertaken |
Year(s) Of Engagement Activity | 2013 |
URL | http://ersnet.org/ |
Description | Keynote lecture British Society of Nanomedicine |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | Keynote lecture at the young researchers meeting in Swansea |
Year(s) Of Engagement Activity | 2017 |
Description | MRS Boston |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Invited speech at the Fall MRS meeting in Boston 2016 |
Year(s) Of Engagement Activity | 2016 |
Description | Nanoparticle Press release |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Type Of Presentation | Paper Presentation |
Geographic Reach | International |
Primary Audience | Media (as a channel to the public) |
Results and Impact | International press release made by QUB in conjunction with MRC Several companies have now approached us about the innovation and patient groups. More engagement anticipated from this in the future 12 months |
Year(s) Of Engagement Activity | 2013 |
Description | RCUK teacher training |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | Yes |
Geographic Reach | Regional |
Primary Audience | Schools |
Results and Impact | Used the opportunity to refresh teachers knowledge of rapidly developing areas, highlighting our own research interests and education about the requirement for animal usage in research Invites to schools to talk about research ongoing at QUB |
Year(s) Of Engagement Activity | 2014 |
Description | School visit |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Type Of Presentation | Workshop Facilitator |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | 30 puils who are interested in undertaking careers with biology background in a career session invited to take part in session again |
Year(s) Of Engagement Activity | 2010,2011,2012,2013 |
Description | SialoGlyco meeting |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Gave a invited lecture at this meeting in California. Stimulated interest in our new drug modality from interested companies in USA, and Japan |
Year(s) Of Engagement Activity | 2017 |