New translational award programme provides a boost for promising dementia projects

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We are delighted to announce the first recipients of the brand-new UK DRI Translation Award programme, an initiative to kick-start promising ideas and projects that have the potential to transform the lives of those affected by dementia.

At the UK DRI, we undertake groundbreaking research, uncover new scientific discoveries and turn this knowledge into new technologies and treatments. When it comes to translating research from bench to bedside, external investment can be difficult to secure without pre-clinical analysis, feasibility studies or proof-of-concept. To address this need, we launched the UK DRI Translation Award programme, giving our researchers the opportunity to secure funds for pre-clinical analysis, drug target validation or other work directly related to finding treatments. Successful researchers can then use the data they acquire to apply for larger scale funding such as a translational grant or seed venture capital funding.

UK DRI Director of Business and Innovation, Dr Kay Penicud, said:

“We’re delighted by the enthusiastic response from our Group Leaders to the call which has been matched by high-quality project submissions. External experts from industry, academia and investment organisations have kindly lent their knowledge and experience to reviewing these applications and have selected four fantastic awardees. I’m looking forward to seeing where these projects lead and their positive impact for people living with dementia.” 

The four awardees of the UK DRI Translation Award Programme are:

Non-invasive brain stimulation intervention to treat sleep impairment in dementia

Dr Nir Grossman (UK DRI at Imperial)
A proposal made in collaboration with Prof Derk-Jan Dijk and Dr Ines Violante (UK DRI Care Research and Technology, based at the University of Surrey).

People living with dementia experience sleep disruptions including frequent waking during the night. The severity of these disruptions is linked to cognitive impairment and recent research suggests a causal effect on the progression of Alzheimer’s disease pathology.

In this study Dr Grossman and colleagues will develop a non-pharmacological intervention for sleep disturbances in dementia that aims to slow or reverse the progression of the disease by rescuing the protective benefits of sleep. Their approach is based on a novel sensory stimulation that augments the brain activity governing sleep. This project aims to provide critical evidence in older adults during night sleep to guide future clinical trials in people living with dementia.

Identification of new inhibitors of inflammation for treatment of neurodegenerative diseases 

Prof Paul Morgan (UK DRI at Cardiff)
A proposal submitted together with Prof John Davis (ARUK Oxford DDI) and Dr Wioleta Zelek (Cardiff University).

Dysregulation of a part of the immune system known as the complement system has been implicated as a driver of inflammation in neurodegenerative disease. However, it remains unclear whether a particular complement activation pathway is predominant in neurodegeneration, with evidence pointing to the alternative activation pathway.

This project will develop high-throughput screening methods to identify inhibitors of the alternative complement pathway. The assays developed will then be used to screen existing libraries to identify promising candidate drug compounds. Following tests for efficacy and stability in cells, compounds will then be verified in animal models that mimic aspects of diseases such as Alzheimer’s. If successful, this project will provide the foundation for further testing with the ultimate aim of developing treatments that target harmful inflammation in neurodegenerative disease.  

Optimisation of CRISPR-Cas9 technology for delivery and gene editing in animal models of diseases such as Huntington’s

Prof Vincent Dion (UK DRI at Cardiff)
Subject to co-funding - To be undertaken in collaboration with Dr Georgina Menzies and Dr Mariah Lelos (Cardiff University) and Prof Annalisa Pastore (UK DRI at King’s)

CRISPR-Cas9 technology has revolutionised modern science, allowing researchers to edit genomes using relatively simple, inexpensive and rapid methods. For a disease that is caused by a genetic mutation, such as Huntington’s disease, application of this technology could prove groundbreaking. However, there are key hurdles to overcome such as gene editing efficiency which are currently a barrier to getting treatments to the clinic.

In this study, Prof Dion and colleagues propose to overcome these problems using new variants of the CRISPR-Cas9 technology. They’ll develop variants with better delivery and greater target efficiency, and then test these in both cellular and animal models of Huntington’s. Lastly, they will investigate whether these variants can be used for classical gene editing and epigenome editing. If successful, this would provide a technology platform for gene and epigenome editing approaches in animal models.

Targeting DNA repair for treatment of Huntington’s disease

Dr Gabriel Balmus (UK DRI at Cambridge)
Subject to co-funding - In collaboration with Prof Sarah Tabrizi (UK DRI at UCL)

In recent years genetic studies have shown that a subset of genes involved in DNA repair are important in the onset and progression of Huntington’s disease. Evidence from both humans and Huntington’s disease animal models suggests that inhibiting just one gene from the DNA-mismatch repair (MMR) pathway, MSH3, can delay the onset of the disease. In this study, Dr Balmus and Prof Tabrizi plan to validate a method that can differentiate specific MMR inhibitors and then screen a range of potential candidates.

There are currently no disease-modifying treatments approved for people with Huntington’s or similar diseases known as the nucleotide expansion disorders. If successful, the discovery of new drug compounds targeting MSH3 would represent a significant departure from other strategies in development but may be a viable treatment method which could be used alongside therapies that target the symptoms of Huntington’s.

If you interested in hearing more about these projects, please get in touch with Director of Business and Innovation, Dr Kay Penicud. UK DRI researchers can find updates on further calls and translation via our dedicated Portal area.

Article published: 30 March 2021