Brain Research UK - Royal College of Surgeons of England joint research fellowship
Neurosurgical trainee Milo Hollingworth was awarded this joint research fellowship in 2022, to take forward research aimed ultimately at improving the way in which drugs are delivered to the site of brain tumours.
The treatment of brain tumours is complicated by the difficulty of getting chemotherapy drugs into the brain at a high enough concentration. The blood-brain barrier is a vital protective mechanism, protecting the brain from toxins in the blood, however it also hampers the passage of drugs. It has been an important aspect of failed therapies in the past, not just for brain tumours but other neurological conditions.
Milo’s research is helping to address this problem by developing new drugs that are effective in the treatment of brain cancer AND can be seen on MRI, enabling location, concentration and activity to be tracked in real-time.
When administering drugs for the treatment of brain diseases it is important to know where the drugs are going and in what concentration. For a drug to work, it must be available at the site of action in its active form at the correct concentration and for an appropriate amount of time.
However the brain is a black box when it comes to drug therapy: we can put drugs in and we can measure outcomes (such as changes to the tumour, and length of survival), but we can't see what is happening within the brain. If there is no effect, we don't know why. Is it that the drug itself isn't effective? Is it because the drug isn't getting to the right target, in a high enough concentration?
Not being able to answer these questions limits our ability to develop effective treatments for brain disease and has limited progress for patients with many neurological conditions, including brain tumours. Not being able to understand why treatments fail makes failure very expensive.
Milo and colleagues have begun to address these questions by developing drugs that are magnetic resonance imaging (MRI) active – that is, drugs that are modified with molecules that are visible using MRI. When injected into the brain, therefore, their location, concentration and activity (‘pharmocokinetics’) can be visualised and monitored.
In particular, the team has developed an MRI-active version of Olaparib, a targeted drug used in the treatment of some cancers, and which has shown some effectiveness against the brain tumour medulloblastoma in laboratory testing.
They will now take this work forward in a translational project that modifies existing drugs into MRI-active forms and studies their effect in vitro. They will then use a specially developed anatomically accurate surgical simulator to study how we can monitor and deliver them during brain surgery.
Milo is based in the Children’s Brain Tumour Research Centre at the University of Nottingham, one of the UK’s leading centres for research into childhood brain tumours.
Taking a break from neurosurgical training to work towards a PhD, he has a particular interest in drug delivery to the brain – including the measurement and monitoring of drug location and activity - as he believes that this holds the key to the successful treatment of neurological disease.
In this multi-disciplinary and ambitious project, Milo is working with Dr Ruman Rahman, who leads programmes in neuro-surgically applied drug delivery at the University of Nottingham; Dr Pete Harvey, an MRI chemist, and Rhian Griffiths, an expert in analytical chemistry.
This work has potential wide-ranging impact including the development of new families of drugs for brain tumours, as well as other diseases of the brain, and improving efficiency of pre-clinical testing of new drugs by identifying drug-delivery failure earlier in translation. In the future, this technology could potentially help optimise dosing schedules for patients, helping to improve efficacy and reduce toxicity.
"This project will test new drugs that can both be seen on MRI and treat brain cancer. This will help us see what we are doing, optimise chemotherapy, improve effectiveness and reduce side-effects for patients with brain cancers and other neurological conditions." Milo Hollingworth
Find out about our other research in this area:
