A clinical trial has been launched at the University of Cambridge that will explore the potential to repurpose the UK-licensed medicine deferiprone for patients with an ultra-rare genetic disease.
Neuroferritinopathy is a progressive and incurable brain disorder affecting about 100 people worldwide which is caused by changes in a gene that produces the ferritin light chain protein.
It leads to the build-up of iron in the brain and usually appears in middle-aged adults, causing severe symptoms and eventually resulting in the loss of speech and swallowing. There are no effective treatments today.
The new randomised placebo-controlled trial, called DefINe, is funded by LifeArca and led by Prof Patrick Chinnery from the Department of Clinical Neurosciences.
The hope is that deferiprone, an affordable oral tablet, will stop the progression of the disease by reducing the iron accumulation in the brain. The drug is already licensed for use in the UK to reduce iron levels in blood conditions like thalassemia.
Prof Chinnery said: “By funding this study, LifeArc has given the first hope of a treatment for affected families. If successful, the trial will open the possibility of using a similar approach for other neurodegenerative conditions linked to the build-up of iron in the brain, including Parkinson’s disease.”
The discovery of neuroferritinopathy came when a surprising number of individuals were found to live in the Lake District. They experienced similar symptoms, but had a series of incorrect diagnoses.
Research into the ancestry of these families by Prof John Burn, a clinical geneticist at Newcastle Hospitals NHS Foundation Trust, discovered a rare mutation caused the progression of the condition and learned that almost all the known cases were likely to be descended from the same ancestor.
He traced this back to the 18th century in Cockermouth in Cumbria and families with the surname Fletcher.
He suggested they may have shared common ancestry with Fletcher Christian - Fletcher being his surname - who was from the region and was known for leading the mutiny on the Bounty in April 1789.
Forty patients will be given the drug for a year and undergo 7T magnetic resonance imaging (MRI) scanning to monitor the iron levels in the brain throughout.
The evidence will be used to apply for licensing in the UK under ‘Exceptional Circumstances’ - an approach often used when the number of affected people is very low and enables the trial to benefit all people with the condition more quickly.
Samantha Denison, one patient hoping to participate in the trial, said: “It came as such a surprise to be informed of the trial and to learn that we have not been forgotten about. To have the chance to be involved in the trial gives me such hope. If it can help to slow or stop the condition progressing, that would be a huge relief. Just to know that by taking part we could also be helping future generations, is amazing.”
LifeArc has contributed £750,000 to the project, while Lipomed, a Swiss life sciences company, has offered to provide both a cost-effective generic form of deferiprone, Deferiprone Lipomed, and a placebo to the trial – a gift in kind worth £250,000.
Dr Catriona Crombie, head of LifeArc’s Rare Disease Translational Challenge, said: “Drug repurposing trials like this are an increasingly effective way of taking treatments that have already been approved and applying them to new conditions and diseases. This will help unlock new treatments for conditions that currently have few, if any, available."
Dr Chantal Manz, chief scientific officer at Lipomed AG, Switzerland, said: “Lipomed is very excited to support this promising study concept in patients with neuroferritinopathy, by providing deferiprone 500 mg film-coated tablets and matching placebo tablets. We recognise the unmet clinical need and the potentially significant benefit of this orally active iron chelator.
“Deferiprone is able to penetrate the blood-brain barrier and may reduce cerebral iron accumulation in patients with this extremely rare, but devastating genetic neurodegenerative disorder, for which no alternative treatments are available.”
