LifeArc and GOSH Charity support a joint funding scheme focused on helping GOSH researchers drive their discoveries towards new tests and treatments for childhood rare diseases.
The 2021 funding round is now closed to new applications
About the LifeArc & GOSH Charity Fund
Researchers based at Great Ormond Street Hospital (GOSH) and the UCL Great Ormond Street Institute of Child Health generate potentially life-changing ideas through lab-based science. The hospital also has world-leading clinical expertise and a unique patient group. Through this funding collaboration, we can deploy our additional expertise in translational research so that more discoveries are ready for the next stage, bringing treatments and cures one step closer to the children that need them.
“LifeArc’s philanthropic activity has a particular focus on rare diseases. GOSH, with its unique patient population, wealth of expertise and aligned goals, is our ideal partner for this project.”
Dr Catriona Crombie, Associate Director Technology Transfer and Philanthropic Fund Manager
The scheme provides funding for translational, milestone-driven projects led by research-active professionals based at GOSH or the UCL Great Ormond Street Institute of Child Health. Qualifying projects should already be on the translational pathway and focused on improving the prevention, diagnosis, prognosis or treatment of rare disease. Projects aimed at developing research tools to improve the efficiency of creating interventions in rare disease are also eligible.
We expect that researchers will continue to develop their intervention by securing further funding from external translational schemes or partnering with industry. We encourage collaborations with industry and other academic partners where these are relevant to the project. Lead applicants may only submit one application per round.
Applications in 2021 needed to:
- address a rare disease medical need
- have a strong scientific rationale
- be a target-driven project with a credible delivery plan and clear milestones
- have a clear route to patient
- make the most of the unique patient populations at GOSH
The following activities are eligible for support:
- developing candidate therapeutic entities (e.g. drug discovery)
- pre-clinical testing of novel therapeutic entities in vitro or in vivo
- pre-clinical validation for repurposed therapeutics
- early-phase clinical trials of novel therapeutic entities (phases 1/2)
- clinical trials of existing therapeutics repurposed for a new indication
- developing and testing novel devices
- developing and testing diagnostics (including biomarker validation)
All modalities of intervention are eligible for support from the scheme, including small molecules, peptides, antibodies, vaccines, regenerative medicine, cell and gene therapy, devices, surgical techniques and psychological approaches.
Application and review process
- The deadline for submission of outline applications was 16th April 2021.
- Applicants successful at outline stage have been invited to submit full proposals.
- Funding decisions are expected in November 2021.
If you have any questions about the programme, please contact firstname.lastname@example.org.
Title: IL13RA2-targeted T-cell therapy for paediatric high-grade gliomas
Principal investigator: Dr Karin Straathof, Child Health Excellence Fellow, Developmental Biology & Cancer Dept, UCL GOS Institute of Child Health and honorary consultant oncology, Great Ormond Street Hospital
Co-investigators: Dr Thomas Jacques, Prof Juan Pedro Martinez-Barbera, Dr Martin Pule, Dr Claire Roddie and Prof Darren Hargrave
Location: UCL GOS Institute of Child Health
Amount funded: £273,702
High-grade gliomas (HGG), referred to as Diffuse Midline Gliomas (DMG), are childhood central nervous system tumours that are very difficult to treat. DMG is the second most common type of primary, high grade brain tumour in children and, sadly, fewer than 10% of children live more than two years after diagnosis.
With this project, Dr Karin Straathof’s team is developing a type of immunotherapy for DMG using immune cells called T cells. T-cells play a vital role in our immune system, recognising and eliminating cells infected with, for example, a virus. However, unlike infected cells, cancer cells often go unnoticed by T cells as they appear similar to the healthy cells from which the cancer has developed. To get around this, and use the power of T cells as cancer therapy, T cells can be engineered to recognise cancer cells using an artificial receptor called a chimeric antigen receptor, or CAR for short.
Early results with CAR T-cell therapy for adults with high-grade gliomas show that these engineered T-cells can attack the tumour. However, the responses are variable and relatively short-lived. This is probably because tumours such as DMG create an environment in which the CAR-T cells can only work for a short period of time. Therefore, in this project, patient T cells will not only be engineered with a CAR which enables the T cells to recognise the tumour, but also with other modules which provide the T cells with extra ‘powers’ to continue to work despite barriers put up by the tumour to avoid CAR-T cell attack.
The team aims to develop a CAR T-cell that responds specifically to a membrane protein, IL-13RA2, which most paediatric HGGs express.
In addition, the team aims to:
- engineer the CAR T-cells with functional modules to overcome challenges at the tumour site
- test different modules using relevant pre-clinical models
- select the most promising approach to translate into a clinical study.
Title: Pre-clinical studies for a stem cell gene editing platform to treat primary immunodeficiencies.
Principal investigator: Dr Alessia Cavazza, Non-Clinical Lecturer, Infection, Immunity & Inflammation Dept., UCL GOS Institute of Child Health
Location: UCL Great Ormond Street Institute of Child Health, Molecular and Cellular Immunology
Children born with severe Wiskott-Aldrich syndrome (WAS) experience wide-ranging symptoms and are at risk of early death without proper treatment. Symptoms of this immunodeficiency disease include easy bruising, bloody diarrhoea and prolonged bleeding following nose bleeds or minor trauma. They are more vulnerable to infection and at higher risk of developing certain cancers.
WAS is caused by errors written into a section of DNA, the X-chromosome. WAS affects almost exclusively boys – around three in every million worldwide – because females have two copies of the X-chromosome and males just one. This gives females an insurance against the errors in one X-chromosome that cause WAS.
As there is no effective treatment, many people born with WAS die before they are 20. The current standard treatment is a bone marrow transplant, but only around 20% of patients can find a suitable matching donor.
Last year Dr Alessia Cavazza’s team published encouraging results for an adapted gene therapy.
Using CRISPR-Cas9 technology – sometimes called ‘molecular scissors’ – they made a physical cut through DNA at the precise place where the WAS gene is usually found. This guided the gene delivery system to slot the corrected gene into the part of the sequence where it is found in a healthy person.
This precise placement of the WAS gene corrected around 60% of cells, while leaving them otherwise unaffected. These cells continued their normal life cycle of maturing into different types of immune system cells.
The team aims in this project to confirm the safety of this particular gene editing technique. If they do, they could start clinical trials at Great Ormond Street Hospital in 2-3 years. The hospital sees around 20-25 patients with WAS each year.
Title: A Phase II Study of a Novel Vitamin Metabolite (CoA-Z) for Pantothenate Kinase Associated Neurodegeneration (PKAN)
Principal investigator: Prof Manju Kurian, Professor of Neurogenetics, Developmental Neurosciences Dept, UCL GOS Institute of Child Health
Co-investigators: Dr Penelope Hogarth and Prof Susan Hayflick (The Spoonbill Foundation)
Location: Great Ormond Street Hospital, Neurosciences Unit at the Institute of Child Health, UCL
Amount funded: £414,842
People with pantothenate kinase-associated neurodegeneration (PKAN) experience a progressive degeneration of the nervous system (a neurodegenerative disorder). MRI scanning has also revealed a build-up of iron in the brain.
Following normal early neurodevelopment, patients increasingly experience problems with their cognitive and physical abilities. Eventually patients are wheelchair-bound, unable to speak and fully dependent for daily living activities.
The disease is caused by a mutation in the protein coding gene PANK2, which provides instructions for making an enzyme called pantothenate kinase 2. This enzyme is active in specialised cellular structures called mitochondria, which are the cell’s energy-producing centres. MRI scans show a build-up of iron in parts of the brain.
There are currently no treatments that significantly modify the condition.
The funding will support UK participation in a Phase 2 safety and tolerability trial of a drug developed by collaborators in the United States that has produced encouraging results in mice. The team’s US partners will conduct a trial with 48 patients. Given the disease rarity, the UK team’s simultaneous trial involving 24 patients will substantially strengthen the study conclusions.
The trial will take two years.