The University of Manchester (UoM) bid for phase 6 of MRC Confidence in Concept (CiC) funding
Lead Research Organisation:
University of Manchester
Abstract
Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
Technical Summary
The Confidence in Concept scheme is a key part of MRC’s translational research strategy and provides annual awards to institutions, to be used flexibly to support the earliest stages of multiple translational research projects. The award can be used by the institution to support a number of preliminary-stage translational projects. The projects supported should aim to provide sufficient preliminary data to establish the viability of an approach –– before seeking more substantive funding. It is intended to accelerate the transition from discovery research to translational development projects by supporting preliminary work or feasibility studies to establish the viability of an approach.
Publications
Ali SM
(2021)
Engagement with consumer smartwatches for tracking symptoms of individuals living with multiple long-term conditions (multimorbidity): A longitudinal observational study.
in Journal of multimorbidity and comorbidity
Beukenhorst AL
(2020)
Engagement and Participant Experiences With Consumer Smartwatches for Health Research: Longitudinal, Observational Feasibility Study.
in JMIR mHealth and uHealth
Dickie B
(2022)
Quantitative kinetic modelling and mapping of cerebral glucose transport and metabolism using glucoCESL MRI
in Journal of Cerebral Blood Flow & Metabolism
Dickie BR
(2020)
Measuring water exchange across the blood-brain barrier using MRI.
in Progress in nuclear magnetic resonance spectroscopy
Harris W
(2022)
In vivo methods for imaging blood-brain barrier function and dysfunction
in European Journal of Nuclear Medicine and Molecular Imaging
Kazi K
(2023)
Examining the variability of multiple daily symptoms over time among individuals with multiple long-term conditions (MLTC-M/multimorbidity): An exploratory analysis of a longitudinal smartwatch feasibility study.
in Journal of multimorbidity and comorbidity
Kyrtata N
(2021)
A Systematic Review of Glucose Transport Alterations in Alzheimer's Disease
in Frontiers in Neuroscience
Swanton T
(2020)
Selective inhibition of the K+ efflux sensitive NLRP3 pathway by Cl- channel modulation.
in Chemical science
| Description | Imaging early blood-brain barrier dysfunction in dementia |
| Amount | £800,509 (GBP) |
| Funding ID | 2453618 |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 08/2020 |
| End | 03/2024 |
| Description | Water exchange in the vasculature of the brain (WEX-BRAIN) |
| Amount | £800,509 (GBP) |
| Funding ID | EP/S031510/1 |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 11/2019 |
| End | 11/2022 |
| Description | Novel treatment for age-related macular degeneration |
| Organisation | Gyroscope Therapeutics |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | Title "Development of a novel treatment for age-related macular degeneration" PI: Prof Paul Bishop Co-I: Dr Simon Clark, Dr Richard Unwin This CiC award funded in vitro experiments with a novel therapeutic, called Coalexin, which we are developing to treat geographic atrophy (GA), also called 'dry' age-related macular degeneration. We plan to deliver this treatment by gene therapy whereby the retinal pigment epithelium (RPE) is transduced and the RPE then secretes Coalexin (a complement inhibitor) and prevents progression of GA. Using the CiC6 funding we undertook successful biochemical and biophysical studies with recombinant Coalexin protein. Importantly, we demonstrated a strong interaction with C3b, and that Coalexin when acting as a cofactor for Factor I, is able to break down C3b as far as C3dg (an advantage over competing therapeutics in development). In addition, we undertook some key ex-vivo experiments which showed that the Coalexin protein can pass through human Bruch's membrane allowing it to reach the choroid, the main site of complement over-activation in AMD, after secretion by the RPE (another key advantage over some competing therapeutic approaches). Part of the CiC6 project involved inserting Coalexin cDNA into an AAV2 expression vector (which was done commercially) and then investigating expression in retinal pigment epithelial (RPE) cells. These experiments provided proof-of-concept that Coalexin can be produced and secreted by RPE cells following Coalexin-AAV2 transduction, however the amount of Coalexin protein produced was low. Following on from this work we entered into a research agreement with Gyroscope Therapeutics (http://gyroscopetx.com/) to undertake in vivo proof-of-concept experiments. As part of this research the Coalexin-AAV2 preparation we had been using was evaluated and was found to be of poor quality, containing a lot of empty vector; this explained the low-level of expression we were obtaining in our in-vitro experiments with RPER cells. Therefore, a new preparation of Coalexin-AAV2 was made which showed improved (but still sub-optimal) expression. This was then used in in vivo experiments using a rodent laser injury CNV model which produced encouraging results. Discussions then took place with Gyroscope Therapeutics around them licensing the technology. However, we were unable to reach agreement over the terms; consequently, this did not progress and our research agreement with Gyroscope Therapeutics was terminated. Instead, we opted to form a University of Manchester spinout company which is called Complement Therapeutics (https://complementtx.com); this is now incorporated. Complement Therapeutics has several assets, but our lead therapeutic, now called CTx001, is Coalexin-AAV. Therefore, the work funded by this CiC award contributed towards the formation of this new company. Complement Therapeutics has now raised EUR 5 Million seed funding. |
| Collaborator Contribution | please see previous |
| Impact | The aim is to develop a treatment for 'dry' age-related macular degeneration, as currently there are no treatments. This is a common cause of visual loss so the societal and economic impact would be vast is we are successful. It is of note that Gyroscope Therapeutics are a UK company, so the economy of the UK would benefit directly. Patent application submitted before project started, filed 15/01/2018 (no. GB1709222.2). A follow on international patent application was subsequently filed. |
| Start Year | 2018 |
| Description | 15th International Workshop on Breast Imaging 2020 |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Squires S, Ionescu G, Harkness E F et al Automatic density prediction in low dose mammography Proc. SPIE 11513, 15th International Workshop on Breast Imaging 2020 |
| Year(s) Of Engagement Activity | 2020 |
| URL | https://spie.org/Publications/Proceedings/Volume/11513?SSO=1 |