Current research projects

Background

Mitochondrial disease is a genetic condition that is caused by a ‘spelling mistake’ in one of our genes. This is sometimes referred to as a ‘variant’ or a ‘mutation’. The diagnosis of mitochondrial disease involves testing a patient’s DNA to try to find the mutation that causes the disease.

The problem is that within a person’s genetic material there can be thousands of spelling mistakes. They are what sets us apart from each other and makes each of us unique. Most are not harmful, but some have the potential to cause disease.

To make things even more complicated, mitochondrial disease can be caused by faults in hundreds of different genes. Finding the gene fault that is responsible for causing a person to have mitochondrial disease can be like looking for a needle in a haystack, or a single spelling mistake in a whole dictionary.

Though DNA testing is available via the NHS, a lack of access to cutting-edge genetic techniques and specialist doctors has led to a backlog of patient data. Many complex cases remain in limbo, leaving patients stuck without a diagnosis for their mitochondrial disease.

Aims of this study

This project will allow scientists and researchers to look closely at the genetic information of patients who are thought to have mitochondrial disease but who haven’t yet received a diagnosis. The project will fund a dedicated team who will look closely at the data that has been gathered so far, re-analysing the genetic spelling mistakes of these patients and using the latest technologies to understand if these faults are responsible for causing mitochondrial disease.

Potential benefit to patients

A genetic diagnosis of mitochondrial disease is essential for patients and families. For families who want to have a subsequent pregnancy, genetic diagnosis is essential to be able to access reproductive options such as prenatal testing during pregnancy and IVF procedures. A genetic diagnosis of mitochondrial disease can also bring closure, as well as allowing access to clinical trials and potential new treatments and helping to guide care and patient management.

There is much to be gained from funding the technology and expertise to improve diagnostic rates. Lily Precision Medicine Diagnostics will benefit those waiting for a diagnosis now, offering affected families a diagnostic service that might not be available through the NHS for several years.

If successful, it’s hoped that this new pipeline will also be adopted by the NHS and form part of the standard genetic testing process for patients in the future. The project has the potential to further increase rates of diagnosis of mitochondrial disease as well as add to our wider understanding of mitochondrial diseases and bring us closer to eventual treatments or even a cure.

Further information

The team have begun processing new cases at sites in London and Cambridge. More cases are expected to be processed as and when other new sites are established across the country. Sites are currently being established at Manchester, Oxford, Moorfields and Guys & Evelina. Later in the year sites are due to expand to include Bristol, Newcastle, QE Birmingham, Birmingham Women & Children’s, St Mary’s Manchester and Sheffield.

Grant information

Official study title – A Lily Precision Diagnostic Service – accelerating introduction of advanced diagnostics for mitochondrial patients in the NHS

Lead investigator – Professor Robert Pitceathly

Medical Institute – University College London (UCL)

Year grant funding awarded – 2022/2023

Project duration – 4 years

Cost - £821,731

Status – Currently recruiting in London and Cambridge, with more sites to follow

Find out more

Background

Mitochondrial disease can result in restricted mobility including ptosis, an inability to fully open the eye. Mitochondrial function is improved by red light and there is evidence that this improves ptosis.

Aims of this study

This pilot study will use red light and measure its ability to improve eye opening in children with mitochondrial disease. Families will be given a specially designed, safe-to-use torch to shine a red light through the closed eyelid for three minutes a day and will visit the hospital for assessments throughout the duration of the study. The results will provide important data about whether this treatment helps to strengthen the muscles in the eyelid and help make it easier to open the eyes.

Potential benefit to patients

This is a safe and relatively simple technology with the potential to improve ptosis in children with mitochondrial disease. The application time for the technology is short and can easily be carried out at home, with potential benefits including increased self-esteem in children. This pilot study may also provide a gateway for further research into red light therapy, with the potential to improve other potential mobility issues that these children face.

Further information

If you would like to find out more about this study please click here.

Grant information

Official study title – Can red light lift droopy eyelids in mitochondrial disease?

Lead Investigator – Prof Glen Jeffery and Dr Annegret Dahlman-Noor

Medical Institute – UCL Institute of Opthalmology

Year grant funding awarded – 2022/2023

Project duration – 24 months

Cost – £54,003

Status – Open to recruitment

Background

Mutations in mitochondrial genes that mainly affect the muscles are known as Primary Mitochondrial Myopathies (PMMs), and can cause symptoms including exercise intolerance, muscle pain (myalgia), fatigue and muscle wasting. A significant obstacle in diagnosing and monitoring progression of PMMs is the ability to accurately assess muscle involvement. Current methods, such as MRI, have been unable to generate robust data, meaning that improved methods to capture changes in muscle are needed. In addition, due to their severity and impact on patient's lives, muscle symptoms are often the target of drug trials - however, the sensitivity of current measures is impacting trial outcomes because they are unable to capture modest drug effects on muscle throughout a trial's lifetime.

Aims of this study

This study will use a special MRI technique to test whether measuring the efficiency of oxygen utilisation by the muscle tissue (the “oxygen extraction fraction”), could be a valid method to identify muscle changes even at the early stages of disease.

Potential benefit to patients

If proven to be effective, this MRI method has the potential to be a new, non-invasive technique to measure the severity of muscle involvement in patients with Primary Mitochondrial Myopathies. This new marker could be used to measure the effectiveness of new drugs being developed for the disease, as well as being used in clinical practice to help support diagnosis and assess disease progression. Importantly, it could also be used as a new outcome measure in clinical trials, potentially replacing exercise testing for patients who are unable to exercise. 

Grant information

Official study title – Measurement of muscle oxygen extraction fraction using MRI as a disease biomarker in primary mitochondrial myopathies

Lead Investigator – Dr Chiara Pizzamiglio and Professor Rob Pitceathly

Medical Institute – University College London

Year grant funding awarded – 2022/2023

Project duration – 24 months

Cost – £92,980

Status – Not yet open to recruitment

Background

The consortium is managed by a Governance Committee comprising international patient advocacy groups including The Lily Foundation (UK), Mito Foundation (Australia), Mitocon Onlus (Italy), People Against Leigh Syndrome (USA) and the United Mitochondrial Disease Foundation (USA).

The Governance Committee works in tandem with international scientific and medical steering committees drawn from the world’s top mito experts.

Aims of this study

The consortium has three areas of focus:

1. Natural history: to improve the understanding of the typical course and development of Leigh Syndrome through a global prospective natural history study
2. Clinical trial endpoints: to define meaningful outcomes that can be measured objectively (physical endurance, relief of symptoms etc.) to determine whether the intervention being studied is beneficial
3. Pre-clinical research: to undertake studies in test tubes or animals that yield preliminary efficacy, toxicity and safety information before moving to the human trial phase.

Potential benefit to patients

Global collaboration of this kind backed by dedicated project grant funding will improve the lives of patients with Leigh Syndrome around the world. A better understanding of Leigh’s disease through building and sharing of natural history data and funding research that is necessary to ensure Leigh Syndrome is ‘trial ready’ will ensure potential treatments are available to patients faster.

Further information

https://leighsyndrome.org/

Grant information

Official study title – Leigh Syndrome Roadmap Study

Lead site – United Mitochondrial Disease Foundation (UMDF)

Medical institute – International collaboration

Year grant funding awarded – 2018/2019

Project duration – 5 years+

Total project funding – $1,000,000; Lily funding £84,000 supported by £3,000 from Leigh Network

Status – Ongoing

Background

The Lily Foundation is providing additional funding to support a pilot study funded by Muscular Dystrophy UK, to test a chemical that could improve muscle weakness in some patients with mitochondrial disease caused by mutations in the mitochondrial DNA (mtDNA). Most patients with mtDNA mutations have a mixture of both normal and mutated mtDNA in the cells of their body, and it is only when the amount of mutated mtDNA exceeds a certain level that disease symptoms appear. A chemical has been identified that is able to promote normal mtDNA but not mutated mtDNA in cells grown in the laboratory, leading to an increase in the amount of healthy mitochondria.

Aims of this study

This study aims to test a drug called 2DG in people with the most common form of mitochondrial disease, caused by a specific mutation, m.3243A>G. Researchers will investigate whether the drug can find its way to human muscle and once there, whether it has the same effect in the body as it does on cells grown in the laboratory.

This small-scale study involving a small number of participants will provide important information on optimal dosing and safety and is essential for establishing the potential benefits of the drug in preparation for a larger clinical trial.

Potential benefit to patients

It is estimated that currently there are around 5,000 patients in the UK with m.3243A>G. and if this pilot study is successful, full clinical trials can commence with more patients. As well as being a potentially effective treatment for people with the m.3243A>G mutation, this treatment also has the potential to benefit those with other mitochondrial diseases caused by mutations in the mtDNA.

Grant information

Official study title – An Experimental Medicine Study To Assess The Safety And Efficacy Of 2-Deoxyglucose In Patients With m.3243G Mutant Mitochondrial DNA

Lead Investigator – Professor Antonella Spinazzola

Medical Institute – University College London

Year grant funding awarded – 2019/2020

Project duration – 24 months

Cost – £ 30,000

Status – Ongoing

Background

Hearing loss is a common problem related to mitochondrial disease, affecting up to one in eight patients. Problems with hearing can have a major impact on communication, social participation and wellbeing. The standard treatment for mild to moderate hearing loss in patients with mitochondrial disease is hearing aids; however, these are often ineffective as they make sounds louder, but not clearer. This can lead to patients feeling dissatisfied with traditional hearing aids, and they may choose not to wear them.

Aims of this study

The EMERALD study will test a new type of technology, called a remote microphone Assistive Listening Device (ALD) which can enhance the use of traditional hearing aids by making it easier to understand speech, especially where there is a lot of background noise. The study will test whether using an ALD can improve hearing and communication and improve well-being and social participation. The study will also assess levels of patient satisfaction and whether the new device is well-tolerated by patients.

Potential benefit to patients

If shown to be of benefit, this new ALD technology has the potential to improve symptoms of hearing loss in patients with mito, resulting in easier communication and improved quality of life.

Further information

If you would like to find out more about this trial click here.

Grant information

Official study title – EMERALD Pilot study: Evaluating the Tolerability and Efficacy of a Remote Microphone (Assisted Listening Device) in Adult Patients with Mitochondrial Disease

Lead Investigator – Professor Gráinne Gorman and Dr Renae Stefanetti

Medical Institute – Newcastle University

Year grant funding awarded – 2021/2022

Project duration – 21 months

Cost – £79,563

Status – Open to recruitment

Supported by a generous donation by My Mito Mission

Background

Mitochondrial DNA depletion and deletion syndromes (MDDSs) are characterised by low levels of mitochondrial DNA (mtDNA) as well as by the build-up of damaged mtDNA molecules in affected tissues.

Often these abnormalities in mitochondrial DNA are caused by a shortage or imbalance of the building blocks of the DNA, which are known as nucleotides. Scientists believe that supplementation of these building blocks could be a promising option for treatment.

Aims of this study

This study will focus on a particular type of MDDS that is caused by mutations in the MPV17 gene. This mutation causes severe liver disease and neuromuscular damage in humans. Researchers will use a MPV17 mouse model, which has the same features of the disease as humans, to test whether nucleoside supplementation is effective in the long-term at restoring mtDNA numbers, preventing the accumulation of damaged molecules in liver and muscle and preventing and reversing the loss of mitochondrial and organ function.

Potential benefit to patients

If successful, this could lead to future trials in human patients with MPV17 mutations, as well as potentially also being extended to treat other mitochondrial DNA disorders in the future.

Grant information

Official study title – Deoxynucleoside-based treatment for mitochondrial DNA disorders

Lead Investigator – Professor Antonella Spinazzola

Medical Institute – University College London

Year grant funding awarded – 2021/2022

Project duration – 14 months

Cost – £ 98,747.31

Status – Ongoing

Supported by a generous donation by My Mito Mission

Background

Epileptic seizures can be a prominent and debilitating symptom of mitochondrial disorders, especially in children. These seizures are often ongoing and very difficult to control. Currently the only way to manage the seizures is with multiple medications, each of which may have unpleasant side effects.

Aims of this study

Transcranial direct current stimulation is a treatment that delivers a very low current and has been shown to calm seizure activity. The technique has been used successfully in a small number of patients under special circumstances. This new study, called TRANSFORM, aims to establish whether this treatment improves seizure control enough to be offered as a new treatment option for a larger number of patients with mitochondrial disease and epilepsy.

Potential benefit to patients

If shown to be effective, this technology has the potential to become a recognised treatment for patients who experience seizures as part of their mitochondrial disease, offering an achievable, accessible option compared to more traditional methods. As well as becoming a mainstream treatment for mitochondrial patients with epilepsy, this treatment could also be expanded to help manage epilepsy in other conditions.

Further information

If you are interested in finding out more, or would like to participate, please click here or contact us:

Prof Robert McFarland at +44 191 2825225, Dr Albert Lim via [email protected] or Katrin Bangel via [email protected] or visit www.isrctn.com/ISRCTN18241112

Grant information

Official study title – TRANScranial direct current Stimulation for FOcal Refractory epilepsy in Mitochondrial disease (TRANSFORM): delayed-start, randomised, double-blinded, placebo-controlled trial

Lead Investigator – Professor Bobby McFarland and Dr Albert Lim

Medical Institute – Newcastle University

Year grant funding awarded – 2019/2020

Project duration – 24 months

Cost – £86,254

Status – Open to recruitment

Background

Involvement of the brain in mitochondrial disease is common. As well as seizures and stroke like episodes, neurological consequences can often include neuropsychiatric symptoms such as anxiety, agitation, emotional dysregulation, depression and/or altered sensory perception. There has been no systematic study of these clinical aspects of mitochondrial disease, which are often missed and can be greatly disabling and distressing for patients.

Aims of this study

This study is being jointly funded with Mito2i and aims to collect detailed information on neuropsychiatric symptoms and brain imaging biomarkers in adult patients with mitochondrial disease. It will also use MRI to look closely at brain images of people with mitochondrial disease.

Potential benefit to patients

Findings from this project will help to guide better clinical care for patients, and the data collected will be invaluable for future clinical trials of new drugs that are aimed at restoring mitochondrial function in the brain.

Further information

If you would like to be involved in this study, or find our more, please click here or contact: Amy Kartar ([email protected]) or Dr Alessandro Colasanti ([email protected]) 

Grant information

Official study title – Neuropsychiatric and Brain Imaging Phenotyping of primary Mitochondrial Diseases

Lead Investigator – Dr Alessandro Colasanti

Medical Institute – University of Sussex in collaboration with University College London

Year grant funding awarded – 2020/2021

Project duration – 18 months

Cost – £79,834

Status – Open to recruitment

Co-funded by Mito 2i and supported by a generous donation from My Mito Mission

Background

Mitochondrial gene editing is a promising therapeutic technology in the field of mitochondrial disease, with the potential to be used for a wide variety of diseases caused by mutations to the mitochondrial genome. The technology is currently being optimised by pre-clinical research at the Minczuk lab and in the future could lead to the development of cures for a wide variety of mitochondrial disease by altering the genetic makeup of dysfunctional mitochondria.

Aims of this study

The study aims to develop a gene therapy technique to remove faulty mitochondrial DNA (mtDNA) in an animal model of mitochondrial disease. The technique makes use of an engineered enzyme that is directed to the faulty mtDNA, where it acts like a pair of scissors to cut the mtDNA. This causes the faulty mtDNA to be removed from the cell, allowing the healthy mtDNA to take its place. The researchers have shown previously that this works in heart tissue in a mouse model of mitochondrial disease, so the next step is to test it in other tissues often affected in mitochondrial disease, including brain and muscle. 

Potential benefit to patients

Researchers believe that removing faulty mtDNA in this way could lead to an improvement in the symptoms seen in patients with mitochondrial disease. It is hoped that the study will provide the vital pre-clinical data on efficacy and safety required to take the next steps towards using this strategy to treat patients. 

Further information – you can read more about this study here and here.

Grant information

Official study title – In vivo mitochondrial genome editing for heteroplasmic mitochondrial disease

Lead Investigator – Dr Michal Minczuk

Medical Institute – Mitochondrial Clinical Genetics Group, Cambridge School of Clinical Medicine

Year grant funding awarded – 2018/2019

Project duration – 48 months

Cost – £ 90,281

Status – Ongoing

Supported by a generous donation from My Mito Mission