MRC launches two £50m centres for cutting-edge gene therapies

The new Medical Research Council Centres of Research Excellence (MRC CoRE) will receive up to £50 million each over 14 years.

The centres will build on the huge progress made in genomics, allowing the genetic basis of many diseases and processes to be identified. Advances in genome editing and other gene therapies have also made it possible to develop treatments for previously incurable conditions.

The centres will take different approaches to translating the advances in genomics into therapies to treat many diseases, such as:

• heart disease
• neurodegenerative conditions like Huntington's disease
• genetic causes of blindness
• many rare genetic diseases that affect children, including those that cause severe infant seizures

One centre, called the MRC/BHF CoRE in Advanced Cardiac Therapies, will be co-funded with the British Heart Foundation (BHF) and will focus on developing gene therapies for heart disease.

The other centre, called the MRC CoRE in Therapeutic Genomics, aims to make rare genetic disorders treatable by enabling the mass production of affordable cutting-edge gene therapies.

The MRC's new CoRE funding model aims to transform biomedical and health research by revolutionising approaches to prevention, early detection, diagnosis, and treatment of diseases by bringing together the very best researchers to tackle the challenge, wherever they are based.

In addition, the centres will be beacons of excellence driving positive changes in research culture, and in training the next generation of pioneers in the field.

A new way of funding bold and ambitious science

Professor Patrick Chinnery, Executive Chair of MRC, said:

The MRC CoREs are a new way of funding bold and ambitious science that seeks to advance our ability to understand diseases, diagnose them at an early stage, intervene with new treatments and prevent diseases of the future.

They will focus on bringing together the brightest scientists to tackle diseases of major medical importance, so that they will really change the landscape and improve the health of the nation.

I am excited to see how the first two centres announced today will transform approaches in advanced therapeutics. We have seen the first green shoots of how advanced gene therapies could transform medicine, such as the mRNA Covid vaccines, or the recent announcement of the NHS approving a gene-editing therapy that could cure blood disorder thalassaemia.

These two CoREs aim to bring these burgeoning technologies to mass fruition to treat many devastating diseases which will also lead to economic growth.

Bring us closer to a cure for heart failure

Professor James Leiper, Director of Research at BHF said:

We are delighted to be funding this centre, which will undertake cutting edge research into gene therapies for heart disease.

There is currently no cure for heart failure, and this centre's vital work focusing on heart repair and regeneration promises to bring us closer to a cure for this debilitating disease.

MRC/BHF CoRE in Advanced Cardiac Therapies

The MRC/BHF CoRE in Advanced Cardiac Therapies aims to develop the first therapies to stimulate heart repair and regeneration in patients following a heart attack and in those with established heart failure, for which there are currently limited effective treatments.

Heart failure affects almost one million people in the UK and more than 65 million people around the world. Heart attacks are the main cause of heart failure because they cause loss of the heart muscle due to an interruption of the heart's blood supply.

To treat heart failure, we need to develop innovative therapies that stimulate formation of new heart tissue to compensate for what is damaged or lost.

Target key processes with the heart tissue

The researchers aim to discover and target key processes within the heart tissue, which can stimulate the proliferation of heart muscle cells, encourage the growth of new blood vessels, and counteract the formation of scars.

Many of these regenerative processes have been identified as occurring naturally in the hearts of other animals, including salamanders and fish, and even in human infants.

The centre aims to develop the first therapies that can reawaken these regenerative processes within the cells of damaged human hearts.

They plan to do this using therapies based on nucleic acids, the building blocks of our genetic material DNA and ribonucleic acid (RNA). These will include messenger RNA (mRNA), similar to the cutting-edge techniques in the COVID-19 vaccines, and small regulatory RNAs. These will be identified through systematic, high throughput genetic screening.

Use viral and non-viral based technologies

The project will use viral and non-viral based technologies to deliver these therapeutic DNAs and RNAs into the cells of the heart. There they will alter the cell's functions, for example to switch a function on or off, or to make a protein.

The researchers will work closely with the Cell and Gene Therapy Catapult and with industry, including AstraZeneca, AskBio and Batavia Biosciences. They will collaborate on tasks, such as screening libraries for therapy targets and accessing gene therapy delivery technologies and with Syncona, a large venture capital firm in London, to drive further investment and progress toward application in patients.

Transformational for heart disease treatment

Professor Mauro Giacca, the Director of the MRC/BHF CoRE in Advanced Cardiac Therapies, from King's College London, said:

There is a tremendous need for new therapies for heart failure and we're now at an exciting moment when the technologies have really progressed to an extent where we can realistically start to develop gene therapies. This could be transformational for heart disease treatment.

Professor Andrew Baker, a Co-director of the MRC/BHF CoRE in Advanced Cardiac Therapies, from the University of Edinburgh, added:

We're building an advance therapy ecosystem to drive translation from pre-clinical into clinical trials all in one place. Working with industry and venture capital we will also train the next generation of scientists in how to get therapies out of the lab and into clinical practice.

Professor Paul Riley, a Co-director of the MRC/BHF CoRE in Advanced Cardiac Therapies, from the University of Oxford, said:

To tackle heart disease, it's critical that any therapy we develop needs to be globally applicable and affordable, so it can be rolled out at cost and imbedded in healthcare systems. Our goal is to bring one or more novel advanced therapies for heart failure to be ready for clinical trials in the first seven years of the programme.

MRC CoRE in Therapeutic Genomics

The new MRC CoRE in Therapeutic Genomics aims to transform the diagnosis and treatment of genetic disorders by enabling the mass development of cutting-edge genetic therapies.

They aim to develop therapies for many devastating genetic disorders that are currently untreatable, such as:

• rare disorders that cause severe seizures in infants and neurodevelopmental delay
• certain types of blindness and immune disorders
• severe neurological disorders such as Huntington's disease

Reprogramme genetic therapies to treat new disorders

Recent breakthroughs in genomics and the first generation of genetic therapies have begun to revolutionise the treatment of a few genetic disorders. However, the process to create, test, and approve each new therapy is too slow and expensive to enable treatments to be developed for the thousands of genetic disorders being diagnosed.

To overcome this, the centre aims to develop processes to take successful genetic therapies and reprogramme them to treat new disorders.

The new centre will also use artificial intelligence approaches to enable scientists to process huge amounts of genetic data from patients at previously unimaginable depth.

Potential to treat thousands of genetic disorders

Professor Stephan Sanders, Director of the new MRC CoRE in Therapeutic Genomics, from the University of Oxford, said:

Reprogramming genetic therapies has the potential to treat thousands of genetic disorders. The new Centre will help create a paradigm shift in the knowledge, infrastructure, technology, and industry regulation so that we can make safe and effective patient-customised therapies en masse."

Professor Jennifer Doudna, founder of the Innovative Genomics Institute, where the University of California team is based, and winner of the Nobel Prize in Chemistry for her role in the discovery of CRISPR gene editing said:

As soon as we discover which genetic mutation is causing a disease, we need established techniques to quickly create a targeted and accessible treatment. Right now, getting each gene therapy approved is a multimillion-dollar exercise that starts from square one each time even when many of the steps are the same.

This isn't economical for rare diseases and isn't necessary in most cases. We need to find a way to develop genetic therapies at affordable prices, and we need to work with regulators and industry to make this happen.

Professor Deborah Gill, Co-Director of the MRC CoRE in Therapeutic Genomics, from the University of Oxford said:

We will also prioritize innovation in research culture, ensuring that science is conducted in an ethical and responsible manner, incorporating feedback from patients and the public, so that the findings are distributed to benefit society.

To achieve our vision, we will recruit talented researchers and students and teach them to consider every step of the way from lab to clinic.

Working with UK and international partners

The centre will work with UK and international partners, including:

• Newcastle University
• University College London (UCL)
• Karolinska Institute (Sweden)
• University of California (Innovative Genomics Institute at UC Berkeley and UC San Francisco in the US)

To ensure that laboratory work translates into patient benefit, the MRC CoRE in Therapeutic Genomics will also work in partnership with:

• patient groups
• clinicians
• international consortia (N=1 Collaborative)
• industry (Danaher, Molecular Devices, IDT, Intellia, Bexorg, La Jolla Labs, the Jackson Laboratory and EveryONE Medicines)
• UK infrastructure (Oxford-Harrington Rare Disease Centre, Rare Therapies Launch Pad, Genomics England and the Nucleic Acid Therapy Accelerator)

Knowledge gained will be shared widely

The researchers will initially focus on developing genetic therapies for disorders of the blood, eye, and brain. The knowledge gained from treating these disorders will be shared widely, enabling these approaches to be extended to increasingly large numbers of disorders and organs by multiple research groups.

Delivering genetic therapies to the blood and eye has already led to clinical success. Blood cells can be extracted, edited, checked, and returned to the body where the 'fixed' cells can replicate, making blood-based immunity disorders a good initial target for genetic therapies.

In the eye, the retina is small, easily accessible by injection, and simple to examine, making it low-hanging fruit for treating cells without removing them from the body. The MRC CoRE in Therapeutic Genomics will focus on treating retinal blindness.

Delivering therapies to the brain remains a challenge

In contrast, while the brain is the organ most frequently affected by rare genetic disorders, delivering most therapies to the brain remains a challenge.

The CoRE will initially focus on antisense oligonucleotides, which can already be delivered to cells in the brain, to treat severe neurological and neurodevelopmental disorders. This includes mutations in glutamate receptors (for example, GRIN2A) or sodium channels (for example, SCN2A) that can cause severe seizures in children.

They will also develop new approaches to delivering genome-editing therapies to the brain.

Top image: Credit: Dimensions, E+ via Getty Images

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