Dr Sara Benedetti wants to maximise the potential of a new stem cell treatment that could stop the toxic build-up of a molecule in the brains of children with Krabbe disease, reducing symptoms and improving life expectancy.
Why this research is vital
Lysosomal Storage Disorders (LSDs), such as Krabbe disease, are caused when the body is unable to breakdown certain molecules the way it should. This leads to a toxic build-up of material, including in the brain, where it can affect the way children think and develop. There are no cures for any LSDs.
Krabbe disease is rare, affecting only 2-3 children a year in the UK, but with around 50 LSDs in total, many more children suffer from related conditions. Many are fatal and in cases where they are not, can still lead to developmental delay, movement disorders, seizures, dementia, deafness, and/or blindness.
Research has recently shown that special cells in the blood stream, known as blood stem cells, could offer hope of a new treatment to reduce the effects of LSDs, including Krabbe disease, on the brain.
Stem cells have the unique ability to turn into almost any cell in the body. Rich sources of stem cells include our bone marrow and our blood. Researchers have recently shown that specially selected blood stem cells are able to enter the brain where they turn into cells called microglial cells, which in turn helped to prevent the build-up of the toxic molecules and prevent nerve damage.
For this treatment to achieve its maximum potential, as many blood stem cells as possible need to able to enter the brain. Because our brain is so precious, the body has a way of carefully managing all the molecules that can get in and out, through a ‘gateway’ known as the blood-brain barrier. (BBB)
Dr Sara Benedetti wants to try and maximise the number of stem cells that can get to the brain by altering the structure of the BBB. They have identified a molecule they know plays a key role. Their aim is to modify its function to see if it helps more of the stem cells reach the brain.
Impact of this project
This work could help relieve some of the most debilitating symptoms of Krabbe disease, which arise from the effect on the brain. Importantly, this work might also help in some of the other LSDs and in other brain conditions.
This project is funded by Sparks, Great Ormond Street Hospital Children’s Charity and Krabbe UK through their national research funding call.