Drug repurposing: old drugs, new tricks

What is drug repurposing?

Drug repurposing means taking an existing medicine which has shown to work for one condition and using it to treat a different condition.

This can even happen by accident – perhaps most famously with sildenafil, commonly known as Viagra. Originally studied for the treatment of high blood pressure and angina, by chance it was found to treat erectile dysfunction. Less accidentally (and less famously), BHF-funded work by Professors Martin Wilkins and Lan Zhao at Imperial College London discovered the benefits of using sildenafil to treat pulmonary hypertension, a condition causing high blood pressure in the lungs, which can be life-threatening.

Repurposed medicines have been important in the search for treatments for Covid-19. For example, an arthritis drug called tocilizumab was shown to support recovery from pneumonia associated with Covid-19.

On average, it costs over £1 billion to produce a new drug.

There are many benefits of repurposing drugs. Firstly, it can be cheaper to repurpose a drug compared to making it from scratch. On average, it costs over £1 billion to produce a new drug. Secondly, drug discovery takes time, because there are many steps that are needed before the drug ends up on the shelf. It typically takes 12 years to develop a new drug from discovery to approval for use in people. Repurposing drugs that have already been studied, and in some cases already approved, could potentially save the NHS billions of pounds every year (because lower development costs should mean lower prices to customers such as the NHS).

The BHF is funding scientists to investigate which drugs can be repurposed to treat people with heart and circulatory diseases.

What drugs could treat dementia?

Vascular dementia is the second most common type of dementia (after Alzheimer’s disease) and is caused by reduced blood flow to the brain. There’s currently no cure. High blood pressure is known to be a major risk factor in developing the condition. 

Research part-funded by the BHF found that amlodipine, a drug used to treat high blood pressure, could help treat vascular dementia or stop it in the early stages. The study, a collaboration between BHF-funded researchers at the University of Manchester and scientists in the USA, looked at what happened when mice with high blood pressure and vascular damage in the brain were given amlodipine.

They found that the treated mice had better blood flow to the brain. Their blood vessels widened, which allowed more oxygen and nutrients to reach parts of the brain that needed it most. The team also found that amlodipine can restore the activity of a protein called Kir2.1, which increases blood flow to active areas of the brain, protecting the brain from the harmful effects of high blood pressure. They now hope to trial amlodipine as an effective treatment for vascular dementia in humans.

Can cancer drugs help heart patients?

When a heart attack happens, the body’s immune cells rush to the damaged heart. But rather than repairing the damage, this immune response can cause further harm to the heart and increase the risk of future heart attack or stroke. 

A study part-funded by the BHF discovered that a cancer drug called aldesleukin could offer a potential solution, by boosting anti-inflammatory cells in patients’ immune systems.

Aldesleukin is used to treat kidney cancer. It works by encouraging the immune system to attack cancer cells. A trial in patients at Addenbrooke’s Hospital in Cambridge has shown that low doses of aldesleukin, when injected under the skin of people who have had a heart attack, increased the activation of immune cells that calm inflammation. This could help to protect the heart. If proven to be effective in larger trials, the researchers hope it could be used to treat patients within the next five years.

BHF-funded research has helped develop treatments to give people with heart failure (a condition where the heart is not pumping blood as well as it should) longer, healthier lives. But there’s currently no cure other than a heart transplant.

With BHF funding, Professor Kairbaan Hodivala-Dilke and her team at Queen Mary University of London are investigating the potential of another cancer drug, cilengitide. Previous work by this team suggested that a low dose of the cancer treatment could be effective at tackling the effects of heart failure. The next steps for the team will be testing this drug further by studying whether it can help stimulate the growth of new blood vessels in injured mouse hearts, with the hope that this can help prevent other changes in the heart’s structure and function linked to heart failure. If this research shows cilengitide holds promise for this condition, it could be tested in a clinical trial to find out if it could help to reduce symptoms for people living with heart failure.

How can we prevent sudden cardiac death?

Every week in the UK, 12 people aged under 35 die unexpectedly from an undiagnosed heart condition, so there is a pressing need to develop treatments targeting the underlying genetic causes. BHF-funded research led by Dr Angeliki Asimaki at St George’s, University of London hopes to uncover existing drugs that could be used to treat arrhythmogenic cardiomyopathy  (also called ACM or ARVC), an inherited heart muscle disorder that can cause sudden cardiac death.

Previous research from the group identified an existing drug that could completely stop the disease – but it was found to be too toxic for use in humans. The drug was shown to reduce the action of a protein called GSK3-beta that plays a role in the development of arrhythmogenic cardiomyopathy.

Every week in the UK, 12 people aged under 35 die unexpectedly from an undiagnosed heart condition

So with BHF support, Dr Asimaki’s team will try different drugs that target the same protein. The researchers have also discovered that inflammation could play a role in the development of ACM. Using this new knowledge, they have identified another potential target for treatment and will be studying the effects of widely used anti-inflammatory drugs, which are known to be safe, with the hope of preventing and reversing this disease.

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