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Key Milestones
A project of this scope and scale has different elements and approaches which will progress in parallel - just like a river, which has streams joining it at different points.
Here are some of the workstreams the CureHeart team will be working on over the next few years. It is hoped that the discoveries and outputs from these will result in at least one of the most promising therapies entering early-stage testing in people living with inherited heart muscle diseases in four to five years’ time.
There are also answers to some of the questions you may have about the project, which can be found lower down the page.
Key Workstreams
1. Patient-facing work
Patients and their family members are central to the CureHeart project, and they are involved as research partners at every stage. Effective patient involvement from the outset and throughout the programme is essential for developing new and effective therapies.
Some of the ways in which patients will be involved include:
- Sharing their experience to help the team prioritise the biggest problems for patients
- Providing patient voices on attitudes to different types of treatment
- Helping the team understand the needs of patients, and what information is important to them
- Helping to recruit participants for trials, and deciding what represents a successful outcome from the patient perspective
Patients also sit on two groups related to CureHeart: the British Heart Foundation (BHF) Oversight Panel, and the Ethics Advisory Group. A patient, and patient representative Joel Rose of Cardiomyopathy UK, also sit on a Scientific Steering Committee. This makes sure patient voices are always part of discussions about the direction of the project as it develops.
Another important focus of this workstream will be to identify and prioritise those groups of patients that are most in need of new genetic treatments.
Combining expertise across a range of areas, including genetic research and advanced heart imaging, the CureHeart team will build a comprehensive picture of disease burden. This information will be used to guide the team and help them decide which groups of patients to target first.
2. Develop genetic therapies
Complex tools are needed for genetic therapies and these tools must be designed specifically for each faulty gene the team wish to treat. Designing the most effective tools is a challenging process which takes time and substantial testing to ensure the therapies are safe and effective.
Two different approaches are being explored.
Antisense silencing is already being used to treat certain other conditions. It doesn’t change the faulty DNA code but stops it producing faulty proteins. Repeated treatments could stop symptoms and disease from developing or progressing.
Gene editing, on the other hand, does alter the DNA in the cells of the heart. It could be used to correct mistakes in a faulty gene, switch a faulty gene off altogether, or boost production from a healthy copy of a gene to compensate for lack of production by a faulty one.
It is crucial to make sure these gene edits act precisely on the mistake being targeted within heart muscle cells, and do not affect other cells of the body. The team will rigorously test editing tools in the laboratory ahead of any trials.
Advancing antisense silencing and/or gene editing therapies to early clinical trials would be a major success in the battle against inherited heart muscle diseases.
3. Target therapies to the site of disease
Many delivery strategies are being developed in parallel, to directly target treatments to the diseased heart muscle. Different delivery strategies will be required depending on the genetic therapy being used, and the team will pair each therapy with the most suitable delivery technique.
Both therapies could be delivered by a simple injection, like many other treatments we already receive. While our knowledge of the best delivery methods for antisense silencing therapies is more advanced, less is currently known about how to effectively deliver gene editing therapies to the heart muscle. The team will consider:
- The best packaging to get therapies to the heart
- Which cells to target, and how many of them need to receive editing to halt symptoms
- The effectiveness and potential side-effects of different delivery approaches
4. Give therapies the greatest chance of success
New genetic therapies could be transformative for some groups of patients living with inherited heart muscle diseases. For those living with more established or advanced cardiomyopathy, new treatments could be less effective because of years of accumulated injury to the heart.
This could make disease more difficult to reverse and could even prevent new therapies from reaching heart muscle cells. To ensure that any new therapy has the best chance of being effective, the team are testing approaches to reduce or reverse existing damage and scarring in the heart to improve the effectiveness of the new genetic therapies.
The power of industry partners
At the right time, pharmaceutical companies will become involved to bring a therapy to the clinic. This is because they have the resources and facilities to manufacture and test the therapies developed to ensure they meet the highest standards required to administer to patients.
What will success look like?
The goal of CureHeart is to develop cures for inherited heart muscle diseases.
Along the way, the team will innovate to develop new gene silencing and editing tools and better packaging systems to deliver those tools to exactly where they are needed most.
By the end of the research programme (late 2027), we hope to be ready to start a first trial in patients.
Frequently asked questions
All forms of cardiomyopathy where a single genetic mutation is known to cause the disease. This includes hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), and arrhythmogenic cardiomyopathy (ACM), where the person has a positive genetic test. The team will identify and prioritise subgroups of those patients most in need of new genetic therapies.
If one of your first-degree relatives has been diagnosed with an inherited heart muscle disease you should be offered clinical and genetic testing to see if you have it as well. This is called ‘cascade testing’ and is vital to make sure people with these conditions receive appropriate treatments. If you are concerned you can speak to a specialist nurse by contacting the BHF Genetic Information Service.
Current treatments for the conditions can help to relieve symptoms or protect against the dangerous heart rhythms that can cause sudden death. They don’t treat the underlying cause or stop the condition progressing, and the heart can become more damaged over time.
Genes are the blueprints that build proteins that we need for our body to function properly. We inherit one copy of each gene from each parent. In some forms of cardiomyopathy, one copy is faulty because of mistakes in the DNA that make up that gene.
The action of the treatment will depend on what problem the DNA mistakes cause. The treatment may boost production of proteins from the healthy copy, or prevent faulty genes from having an effect. Other gene-editing treatments may correct the DNA mistake by rewriting or replacing that section of the gene.
The team aims to develop treatments that are both effective and safe, but it is possible that there will be short and longer term adverse effects. For this reason, the CureHeart team will first test the treatments fully in the laboratory, following established ethical principles.
The CureHeart team will set up clinical trials and work with regulatory bodies to measure safety and effectiveness in patients over a number of years.
Yes, because the gene therapies that CureHeart will develop will only affect the genes in the heart muscle and not reproductive cells, which means that these changes can’t be passed onto future generations.
If successful, where genetic testing reveals that a child has inherited a cardiomyopathy, they could receive a CureHeart treatment to prevent symptoms ever starting.
Before taking part in any clinical trial, you should discuss it extensively with your cardiomyopathy specialist, and there are a number of criteria that you will need to meet to be accepted on to a trial. You should also choose to enter a trial that you and your specialist believe may benefit you, whether that be based on CureHeart treatments or any other.
Some clinical trials make use of an adeno-associated virus (AAV) to deliver the therapy. These are the shells of viruses that scientists can use to transport cargo into cells and allow medication to be transported to the area of the body where it is needed most. Taking part in a trial using AAVs to treat any condition may mean you cannot take part in CureHeart trials that also use them. This is because your body may develop an immune defence against AAVs, which may make any further treatments using AAVs ineffective.
CureHeart is developing several therapeutic approaches to maximise the chances of changing the lives of people living with inherited cardiomyopathies. Depending on the precise technology used for each of them, some therapies would be a one-time treatment whereas others might require repeat treatment to effectively protect the heart.
Gene editing therapies have recently been introduced to treat a small number of other conditions, with several others currently in clinical trials. So far, however, researchers have not been able to provide this for heart muscle conditions.
It is difficult to get gene editing technologies into heart muscle cells, and to change enough of these cells to restore normal heart function. This is part of the challenge that CureHeart aims to overcome.
Depending on which technology appears most promising, the team may have everything they need to start early-stage clinical testing of their most promising technologies within the lifetime of the BHF-funded research programme. The final progress review of the CureHeart project will be in early 2028. This will also depend on which type of cardiomyopathy, and which problem in which gene, is targeted first.
A clinical trial typically takes several years to complete. If successful, the next step is getting regulatory approval. This is because all new medical treatments and their component parts need to be carefully regulated to ensure that they perform to high standards.
In the UK, approval and decisions on which patients might benefit are decided by the Medicines and Healthcare products Regulatory Agency (MHRA). In the US this is by the Food and Drug Administration (FDA), and in the EU by the European Medicines Agency (EMA).
Once a new therapy receives regulatory approval in the UK, the National Institute for Health and Care Excellence (NICE) then evaluate it for NHS use, considering clinical effectiveness and value for money. We would hope that any therapy developed by CureHeart would be made available in the NHS. Treatment availability in other countries will depend on their own regulatory bodies.