Following trials to assess their safety and efficacy, drugs are usually approved for use in the clinic by the regulatory authorities for the treatment of a specific disease. This is referred to as the drug “license” – the condition for which it can be prescribed. However, an increasing number of studies have shown that drugs which have been approved for one condition may be effective in the treatment of others. This is referred to as drug repurposing. The advantage of this approach is that the drugs will have passed the initial safety stage of drug development so that they can immediately go into clinical trials.
How can we identify these drugs?
A drug acts by influencing certain chemical reactions, or pathways, within a cell. This usually influences how the cell works. In the brain, for example, it may cause nerve cells to produce chemicals that are associated with the transmission of electrical activities between cells. However, in certain circumstances, modification of these pathways may damage or even kill cells. This is what we want to harness in order to destroy the cells within brain tumours. In addition to drugs that are in use for other conditions, there may be others which had been tested in trials for another condition, but failed to show any significant clinical benefit for that specific illness. It is worthwhile testing some of these based on our knowledge of how they work. Brain tumour cells grown in a dish in the laboratory can be used to carry out initial tests to determine whether the drug will kill the cells. We can also grow normal nerve cells in the lab. This is important because we want the drug to target tumour cells without harming the other brain cells.
Are there other factors that we should consider?
One of the challenges associated with treating brain tumours is the ability of the drug to get into the brain. The blood brain barrier – which is a membrane that surrounds the brain – prevents many drugs from entering the brain. But Prof Geoff Pilkington at the Brain Tumour Research centre at the University of Portsmouth has developed a model of the barrier. So as well as being able to test whether the drugs may be effective to treat tumours, we can also assess their potential ability to enter into the brain.
Is there any evidence of this for the treatment of brain tumours?
Research funded by Brain Tumour Research has demonstrated that a specific formulation of aspirin may enter into the brain and could be effective for the treatment of glioblastoma . This research is still at an early stage, and will need further studies before clinical trials can begin. However, the results to date are promising. Our research centre at Portsmouth have also demonstrated that an anti-depressant drug, clomipramine, may also be able to kill tumours. However, this drug may have harmful side effects so the researchers are trying to understand the mechanisms by which it may kill cells and whether there may be other drugs which can have the same effect on the cells without the side effects. Studies have also been carried out on the anti-epileptic drug sodium valproate with mixed results. While there is no indication that people who take the drug over a long period of time have a lower incidence of brain tumours, there is some evidence that it may act to increase the efficacy of temozolomide, which is the primary drug use to treat brain tumours.
So, what is the next stage?
The UK Department of Health is leading a new initiative to develop guidelines for the repurposing of drugs. This is a key component of Brain Tumour Research’s manifesto and we will be working very closely with this group to develop guidelines to get potential repurposed drugs into clinical trials as quickly as possible. We will also be highlighting this as a priority for the research centres