Analysis of healthy and leukodystrophic developing brain - v.1
Research type
Research Study
Full title
Analysis of tissue samples from healthy and leukodystrophic developing brains to determine the transferability potential of an experimental treatment.
IRAS ID
197685
Contact name
Freyja K McClenahan
Contact email
Sponsor organisation
University of Cambridge
Duration of Study in the UK
1 years, 9 months, 1 days
Research summary
The analysis of human brain tissue lies within a larger project, in which we seek to develop a new treatment for children with hypomyelinating leukodystrophies (HLDs). HLDs result from a series of genetic mutations that affect the ability of oligodendrocytes, the myelinating cells of the central nervous system, to effectively wrap nerve fibres. Defective myelination leads to motor and cognitive deficits, language problems, and often to early lethality. Cell transplantation is an attractive candidate for the treatment of these disorders, but existing approaches come with caveats that may limit their application. For example, the reprogramming of patient skin cells to neural stem cells (NSCs) may produce cells that behave abnormally after transplant, and the use of NSCs from donated embryos suffers from limited availability of cells and the requirement for lifelong immunosuppression. Therefore, our aim is to develop a method to isolate a patient’s own neural stem cells, correct leukodystrophic mutations, and transplant these cells back into the patient to restore proper myelination.
The major neural stem cell niche in the mammalian forebrain is the subventricular zone (SVZ), located adjacent to the lateral ventricles. Here, NSCs reside beneath a layer of ependymal cells that line the ventricular surface. Our plan is to ablate the ependymal cell layer, allowing for the release of NSCs into the cerebrospinal fluid within the lateral ventricles. To achieve this we are injecting a cocktail consisting of neuraminidase, an enzyme that targets particular lectins on the surface of ependymal cells, and an antibody that blocks β1 integrins, which are integral components of the adhesions between SVZ cells, into the lateral ventricles of rats. To determine if this treatment is transferable to human patients, we will need to confirm the expression patterns of these targets in tissue from the developing brains of healthy and leukodystrophic infants.REC name
West of Scotland REC 5
REC reference
16/WS/0038
Date of REC Opinion
3 Feb 2016
REC opinion
Favourable Opinion