UCL to work with UK and international partners to make rare genetic disorders treatable

The two new Centres will build on the huge progress that has been made in genomics – allowing the genetic basis of many diseases and processes to be identified – and advances in genome editing and other gene therapies, which have 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 Huntingdon’s disease, genetic causes of blindness, and many rare genetic diseases that affect children, including those that cause severe infant seizures. 

Researchers from the UCL Queen Square Institute of Neurology will be working with UK and international partners on the MRC Centre of Research Excellence in Therapeutic Genomics, which aims to make rare genetic disorders treatable by enabling the mass production of affordable cutting-edge gene therapies. 

The other centre, called the MRC/BHF Centre of Research Excellence 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 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.  

Professor Sarah Tabrizi, UCL Queen Square Institute of Neurology, Co-investigator for the MRC Centre of Research Excellence in Therapeutic Genomics said: “This new Centre represents a real step forward in the field of genomics. Our aim is to use AI to analyse a vast amount of data. We can use this information to take successful genetic therapies and reprogramme them to treat new disorders. This will accelerate the development of treatments and ultimately help countless families affected by genetic diseases. 

Dr Jasmine Donaldson, UCL Queen Square Institute of Neurology, Co-investigator for the MRC Centre of Research Excellence in Therapeutic Genomics said: “Rare diseases impact around 300 million people globally, but only a fraction of these diseases have approved treatments. Reprogramming genetic therapies has the potential to treat thousands of genetic disorders, leading to safe and effective patient-customised therapies for many.” 

Professor Patrick Chinnery, Executive Chair of the Medical Research Council, 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.” 

More about the MRC Centre of Research Excellence 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, and severe neurological disorders such as Huntington’s Disease. 

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. 

The Centre will work with UK and international partners, including Newcastle University, University College London (UCL), the Karolinska Institute (Sweden), and the University of California (Innovative Genomics Institute at UC Berkeley and UC San Francisco in the USA). The CoRE 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, EveryONE Medicines), and UK infrastructure (Oxford-Harrington Rare Disease Centre, Rare Therapies Launch Pad, Genomics England, the Nucleic Acid Therapy Accelerator) to ensure that laboratory work translates into patient benefit. 

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 CoRE will focus on treating retinal blindness. 

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, for example, mutations in glutamate receptors (e.g. GRIN2A) or sodium channels (e.g. SCN2A) that can cause severe seizures in children. They will also develop new approaches to delivering genome-editing therapies to the brain. 

Related:

• Source: UKRI press release
• Professor Sarah Tabrizi's academic profile
• Dr Jasmine Donaldson's academic profile

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