Past research projects
Can increasing rates of mitochondrial recycling help reduce the risk of cardiomyopathy in mitochondrial disease? Professor Jo Poulton’s lab-based research uses cells to test whether increasing mitochondrial recycling could help reduce the risk of cardiomyopathy (enlargement of the heart muscle) in patients with m.4300A>G mutations.
Background
Mitochondrial diseases can affect any part of the body but tend to affect organs that require a lot of energy to function. Patients with mitochondrial disease caused by the genetic mutation ‘m.4300A>G’ often develop serious problems with their heart muscle (cardiomyopathy), which can be fatal unless they have a heart transplant. Previous studies have shown that increasing the rate of mitochondrial recycling through a process called mitophagy could potentially benefit cells with mitochondrial DNA mutations.
Aims of this study
This study aims to test whether a drug known to increase mitophagy could benefit this group of patients by reducing the risk of developing cardiomyopathy. The study will also test whether increasing mitophagy rates could be beneficial in other types of mitochondrial disease thus broadening the scope of the research.
Potential benefit to patients
This drug is already widely used for another medical condition so if successful, could be a candidate for fast track to mitochondrial patients and has the potential to treat individuals before symptoms present which would greatly reduce disease burden.
Grant information
Official study title – An investigation into a driver of mitophagy in personalised treatment for mitochondrial disease
Lead Investigator – Professor Jo Poulton
Medical Institute – Oxford University
Year grant funding awarded – 2021/2022
Project duration – 12 months
Cost – £63,143
Improving understanding of POLG disease Dr Nicola Lax’s project is jointly funded by The POLG Foundation and The Lily Foundation, and aims to perform an extensive literature review to develop greater understanding of POLG-related mitochondrial disease.
Background
Genetic mistakes in a gene called ‘POLG’ are associated with mitochondrial diseases in which people typically have a reduced amount or quality of mitochondrial DNA (mtDNA). This depletion of mtDNA can affect energy generation in affected tissues and can cause a spectrum of POLG-related mitochondrial disorders which present with a wide range of debilitating symptoms.
Aims of this study
The aim of the project is to perform an extensive review of the published literature to provide a deeper understanding of particular aspects of POLG-related disease.
Potential benefit to patients
Developing a greater understanding of POLG disease will lead to benefits for patients, including the identification of potential therapies and the generation of consensus guidelines for the clinical management of POLG disease.
Grant information
Official study title – A Systematic Review of Animal and Cell Models of PolG Disease
Lead Investigator – Dr Nicola Lax, Professor Gráinne Gorman & Professor Robert McFarland
Medical Institute – Wellcome Centre for Mitochondrial Research, Newcastle University
Year grant funding awarded – 2020-2021
Project duration – 12 months
Cost – £36,000
Status – Complete awaiting publication
Part funded by the POLG foundation
Using animal models to test new treatments for Mitochondrial DNA Depletion Syndrome Professor Rita Horváth and the team at Cambridge University are developing new Zebrafish models to test potential treatments for MDDS.
Background
Mitochondrial DNA Depletion Syndrome (MDDS) is a mitochondrial disease that is characterised by low levels of mitochondrial DNA (mtDNA) in tissues that require lots of energy, such as the skeletal tissue, liver and central nervous system.
Aims of this study
This study aims to develop animal (Zebrafish) models which have the same disease features as humans, and then use these to test potential new treatments for MDDS. One particular treatment is nucleoside supplementation, which aims to rebalance levels of mtDNA in affected tissues by providing the chemical ‘building blocks’ needed to allow the mtDNA to work effectively.
Potential benefit to patients
There is currently no cure for MDDS, and this research could be an important step in developing a treatment in humans that improves some of the clinical symptoms associated with the condition.
Grant information
Official study title – Testing new treatment options in zebrafish models of mitochondrial DNA depletion syndromes
Lead Investigator – Professor Rita Horváth
Medical Institute – Cambridge University
Year grant funding awarded – 2018/2019
Project duration – 24 months
Cost – £62,432
Status – Complete
Developing guidelines for the assessment of balance disturbances in mitochondrial disease Dr Rob Pitceathly’s team at UCL will test new guidelines for the assessment of balance disorders in people with mitochondrial disease.
Background
The diagnosis of the cause of dizziness or unsteadiness can be complicated in people with mitochondrial disease. Different parts of the body can affect how well we balance, and mitochondrial disease can affect these different parts. It can therefore be difficult for medical professionals to identify the cause of these balance problems for each person.
A recent study found problems with the inner ear system were a common cause of dizziness and unsteadiness. This is the first time this has been shown in a large group of people with mitochondrial disease. Patients with mitochondrial disease could therefore have an important opportunity to access targeted physiotherapy to improve symptoms and quality of life.
Aims of this study
The study will support the validation of assessment guidelines that help understand the cause of balance disturbance, which will allow for earlier identification and improved management of these disabling symptoms. The guidelines will be tested with 100 patients to ensure it is reliable, with the overall aim to be used more widely to help people with mitochondrial disease.
Potential benefit to patients
This framework could help doctors and physiotherapists identify the cause of balance problems and allow quick access to rehabilitation. By developing and testing this framework it is hoped that people with dizziness and balance problems will be able to access targeted therapy intervention more easily, which will help to reduce symptoms, improve balance and safety, reduce falls and improve quality of life.
Grant information
Official study title – Validation of an assessment framework to improve the diagnosis and management of vestibular dysfunction in mitochondrial disease
Lead Investigator – Dr Rob Pitceathly
Medical Institute – University College London
Year grant funding awarded – 2018/2019
Project duration – 24 months
Cost – £84,742
Status – Complete
Treatments for RRM2B Depletion Syndrome & Natural History Study Dr Gorman and the team at Newcastle University aim to develop a greater understanding of RRM2B-related mitochondrial disease whilst also developing new drugs for the condition.
Background
Clinical trials for any kind of mitochondrial disease can be greatly improved by ensuring that patients are ‘trial ready’. Part of this process involves studying the clinical features of patients in detail, which allows the development of meaningful outcome measures that can be used to determine if a treatment is having a clinical benefit.
Aims of this study
The Lily Foundation is funding a study that aims to collect this information for patients with mitochondrial disease caused by a genetic fault in the gene RRM2B. This research project also aims to develop new drugs that could potentially be used to treat patients with this type of mitochondrial disease and to test these drugs in cell models derived from patient skin cells.
Potential benefit to patients
Gathering this patient data will be vital in developing new natural history data for this rare genetic disorder and could serve as a comparator for future drug trials. Having a greater knowledge about the most burdensome symptoms and difficulties faced by patients with mutations in the RRM2B gene will also help future service provisions prioritise areas of care for these patients.
Grant information
Official study title – Towards devising a therapeutic strategy for patients with recessive RRM2B-related mitochondrial disease
Lead Investigator – Grainne Gorman
Medical Institute – Newcastle University
Year grant funding awarded – 2017/2018
Project duration – 18 months
Cost – £144,166
Co-funded by Mito Foundation
Enzyme Replacement Therapy for MNGIE Lily funding aims to contribute to Dr Bax’s research into a new therapy for MNGIE, by finding markers in the blood that can help measure the effectiveness of treatment.
Background
Mitochondrial neurogastrointestinal encephalopathy (MNGIE) is a rare mitochondrial condition that is caused when a gene fault affects the enzyme responsible for removing certain biological molecules from the body. When the enzyme doesn’t work properly, the molecules begin to build up which causes damage to the mitochondria.
A team based at University of London are due to begin a clinical trial to test a therapy for MNGIE where the missing enzyme is added to the patient’s own red blood cells, resulting in the unwanted biological molecules being removed from the blood.
Aims of this study
As part of the clinical trial, The Lily Foundation is funding research to test whether a biomarker found in the blood can accurately measure the effectiveness of the new treatment.
Potential benefit to patients
This study will help improve overall understanding about the clinical course of MNGIE, leading to improved diagnosis and management. In addition, finding biomarkers that can accurately measure the effectiveness of new therapies will be vital in getting new drugs for mitochondrial diseases approved.
Grant information
Official study title – Enzyme Replacement Therapy for MNGIE (Mitochondrial Neurogastrointestinal Encephalomyopathy) – Biomarker Development
Lead Investigator – Dr Bridget Bax
Medical Institute – St George’s, University of London
Year grant funding awarded – 2017/2018
Project duration – 24 months
Cost – £36,796
Status – Complete
Preventing Mitochondrial Cardiomyopathy Dr Chris Carroll at St George’s is using a mouse model to test a treatment for enlargement of the heart, a common symptom in mitochondrial diseases.
Background
An unhealthy enlargement of the heart (known medically as hypertrophic cardiomyopathy) is a common symptom in mitochondrial diseases that can eventually lead to heart failure and premature death. Previous research has identified a specific set of chemical reactions (known as a metabolic pathway) that may be more active in patients with mitochondrial disease and are driving the enlargement of the heart.
Aims of this study
This study will test whether a drug that is known to reduce the activity of this metabolic pathway can be used to prevent or slow down disease progression in a mouse model of mitochondrial heart disease.
Potential benefit to patients
This research could be of huge benefit to many patients with mitochondrial disease, which if successfully translated to humans has the potential to increase life-expectancy in those with the disease.
Grant information
Official study title – Investigating the pathways involved in mitochondrial cardiomyopathy
Lead Investigator – Dr Christopher Carroll
Medical Institute – St George’s, University of London
Year grant funding awarded – 2017/2018
Project duration – 18 months
Cost – £53,000
Status – Complete
Maximising the potential of Nicotinamide Riboside as a possible treatment for mitochondrial disease Dr Rob Pitceathly will investigate the potential to increase uptake of Nicotinamide Riboside (vitamin B3) in the bloodstream of patients with mitochondrial disease, increasing the number of healthy mitochondria and reducing symptoms.
Background
Nicotinamide Riboside (NR) is a form of vitamin B3 that has been shown to increase the number of healthy mitochondria in animal models of Mitochondrial Disease. This could benefit patients by reducing some of the symptoms of Mitochondrial Disease. However, when taken in its current form, only low levels of NR reach the bloodstream meaning that its effects are limited.
Aims of this study
This Lily-funded research aims to improve the uptake of Nicotinamide Riboside into the bloodstream and maximise the positive effects on mitochondria.
Potential benefit to patients
If successful, this research could lead to clinical trials of NR as a potential treatment for patients affected by mitochondrial disease.
Grant information
Official study title – Development of Novel Nicotinamide Ribosome Formulations to treat Mitochondrial Diseases
Lead Investigator – Dr Rob Pitceathly
Medical Institute – University College London
Year grant funding awarded – 2016/2017
Project duration – 15 months
Cost – £83,686
Status – Complete
TRID therapy for mitochondrial diseases Professor Rahman will investigate whether a novel treatment, called ‘Translational Read-through Therapy’, has the potential to become an effective therapy for mitochondrial diseases.
Background
Mitochondrial diseases are caused by mutations in the genetic code found within our cells. Some of these mutations change the genetic code in such a way that the cell is unable to produce the protein it needs for mitochondria to work. A certain type of drug, known as ‘translational read-through inducing drugs’ (TRIDs) may enable the cells to ignore the gene mutation so that protein production can still occur.
Aims of this study
The Lily Foundation is funding research to test the effectiveness of TRIDs on cells taken from patients with mitochondrial disease caused by various gene mutations.
Potential benefit to patients
If effective, these drugs could potentially be used to treat a wide range of mitochondrial diseases and benefit many patients.
Grant information
Official study title – Translational Read-Through Therapy: A Novel Pharmacological Strategy for Mitochondrial Disease
Lead Investigator – Prof Shamima Rahman
Medical Institute – UCL Great Ormond Street Institute of Child Health (ICH)
Year grant funding awarded – 2016/2017
Project duration – 24 months
Cost – £50,000
Status – Complete
Can a low residue diet improve gut symptoms in patients with mitochondrial disease? Dr Gorman and the team at Newcastle University will test the effectiveness and acceptability of a low residue diet in reducing gut symptoms in patients with mitochondrial disease.
Background
More than 60% of patients with mitochondrial disease experience gut symptoms that can have a significant impact on their health and quality of life. These symptoms include abdominal pain, bloating and severe constipation, and result from the slow movement of food and stool through the gut due to malfunctioning mitochondria.
Aims of this study
This study aims to assess whether a low residue diet (LRD) is well tolerated and able to improve gut symptoms in patients with mitochondrial disease. A low residue diet involves limiting fibre intake and certain foods that stimulate bowel contractions, making it easier for the gut to digest food and easing the passage of stools through the bowel.
Potential benefit to patients
This study will provide useful information as to whether a low residue diet is acceptable and improves gut symptoms in patients with mitochondrial disease. If successful, we hope the findings will support funding a larger trial to investigate the benefits of the diet.
Grant information
Official study title – Phase II feasibility study of the efficacy and acceptability of a low residue diet in adult patients with mitochondrial disease
Lead Investigator – Grainne Gorman
Medical Institute – Newcastle University
Year grant funding awarded – 2016/2017
Project duration – 12 months
Cost – £78,783
Status – Complete
You can read the results from this study here.