What did the project achieve?
“Encouraging results from our laboratory experiments suggest the possibility that an existing drug used to treat iron overload could help boys with Pelizaeus-Merzbacher disease,” says Professor David Rowitch of the University of Cambridge. “Although it’s still early days, repurposing this medicine offers hope for affected families of a potentially effective new treatment that could help slow down or stop the progression of this devastating disease.”
Pelizaeus-Merzbacher disease (PMD) is an extremely rare, inherited condition that affects the myelin sheath that protects nerve cells in the brain and spinal cord and helps with the transmission of nerve impulses. Affected boys can experience a range of symptoms – including movement difficulties, balance and speech problems and learning delays – that vary in severity but usually get worse over time. Sadly, with no effective treatments, children with the most severe form are unlikely to live beyond their 15th birthday.
“We used cutting-edge stem cell technologies to generate myelin-producing nerve cells using skin cells from boys affected with PMD,” says Professor Rowitch. “In our experiments, we found that these cells unexpectedly die due to the effects of iron exposure – and because of this, they don’t produce myelin as they should.”
The team then tested the effects of an existing drug that works by reducing iron levels – both on these patient-derived nerve cells and another laboratory model of PMD.
“We found that treatment with this iron-depleting drug helps the faulty nerve cells to function properly – and importantly, they can then produce myelin,” says Professor Rowitch. “We are now hoping to set up a clinical trial in Europe to explore whether this medicine could be a safe and effective treatment for children with PMD.”
A major advantage of repurposing an existing medicine, compared to developing an entirely new drug from scratch, is that effective treatments should get to patients faster.
This research was completed on
Pelizaeus-Merzbacher disease (PMD) is an inherited condition that affects a child’s brain and spinal cord. Although extremely rare – with estimates suggesting it affects between two and five of every million male babies born – it can be devastating.1 Children can experience a range of symptoms, including difficulties with movement, balance and speech and delayed learning. Sadly, with no cure, children with the most severe form are unlikely to live beyond the age of 15 years. Professor David Rowitch at the University of Cambridge is investigating whether existing drugs used to treat other diseases could also be effective new therapies for PMD. He hopes these could offer a brighter future for children affected by this devastating condition.
How are children’s lives affected now?
Pelizaeus-Merzacher disease (PMD) usually affects baby boys and is caused by gene faults that affect the myelin sheath, which protects nerve cells in the brain and spinal cord and helps with the transmission of nerve impulses.
Myelin is a vital component of our nervous system – so when something goes wrong, this has devastating consequences. PMD is one of a group of rare, progressive diseases called leukodystrophies, which are all caused by problems with the myelin sheath.
Children with PMD experience a range of symptoms – including muscle stiffness or spasms, movement difficulties, balance and speech problems, and learning delays – that can vary in severity but usually slowly worsen over time.
Tragically, children with the most severe forms of the disease often lose their lives before their tenth birthday. But others will grow up to live into their sixties.
“Sadly, there is currently no cure for PMD – doctors can only prescribe medications to help alleviate a child’s symptoms, such as seizures and muscle spasticity,” says Professor Rowitch. “New treatments are desperately needed that can slow down or stop the disease from progressing.”
How could this research help?
“We are aiming to use existing drugs to treat PMD, offering new hope for children affected by this devastating condition and their families,” says Professor Rowitch.
The team has previously developed new cutting-edge stem cell technologies to create myelin-forming nerve cells from PMD patient skin samples. They are using this experimental cell model to develop and test potential new treatments.
“We have previously discovered that existing drugs already used to treat other conditions, can correct what’s going wrong in these patient cells,” says Professor Rowitch.
His team will now investigate whether these drugs are also effective at restoring myelin production in cells from other PMD patients with different genetic faults. They will also carry out experiments to find out more about how the biological mechanisms targeted by these drugs are involved in the disease.
“If our results are promising, our next step will be to test the most promising drug in a clinical trial involving patients with PMD,” says Professor Rowitch. “We also hope it could help children with other leukodystrophies.”
- NIH U.S. National Library of Medicine: Genetics Home Reference: Pelizaeus-Merzbacher disease: https://ghr.nlm.nih.gov/condition/pelizaeus-merzbacher-disease#statistics [Website accessed 29 December 2017]
|Project Leader||Professor David H Rowitch, MD PhD ScD|
|Project Location||Wellcome-MRC Cambridge Stem Cell Institute, Department of Paediatrics, University of Cambridge|
|Project duration||One year|
|Date awarded||14 December 2017|
|Project start date||2 January 2018|
|Project end date||1 January 2019|