Searching for a cure: Hunter syndrome and gene therapy

by YPU Admin on October 24, 2016. Tags: Gene Therapy, Health, Hunter Syndrome, medicine, PhD, Research, and UoM

Introduction

My name is Helene Gleitz and I am a 2nd year PhD student in Medicine. After getting my international baccalaureate in Switzerland, I studied Biomedical Materials Science in Manchester and graduated in 2013. I then applied for a research master’s degree (MRes) in Tissue Engineering for Regenerative Medicine, where I spent 8 months working in a gene therapy lab. In fact, I enjoyed my master’s project so much that I applied for a PhD in the same lab to study gene therapy.

My PhD investigates a rare paediatric genetic disease called mucopolysaccharidosis type II, or Hunter syndrome, that occurs almost exclusively in males. I am looking to develop a gene therapy through the use of haematopoietic stem cells, which are cells involved in the immune and blood systems.


In Depth

Hunter syndrome is caused by mutations in the IDS gene present on the X-chromosome and different mutations affect the severity of the disease. Mutations in the IDS gene affect the IDS enzyme, which is involved in the degradation of complex sugars called glycosaminoglycans (GAGs). When degradation and recycling of large molecules are altered, complex sugars accumulate in every organ in the body and things start to go haywire.

In the most severe form, young children show signs of neurodegeneration, behavioural problems and cardiorespiratory complications amongst many other symptoms. Lifespan is also significantly reduced, with most patients dying in teenage years. Unfortunately, there is currently no cure for the severe form and replacing the missing enzyme (known as enzyme replacement therapy) has no impact on the brain.

The goal of my PhD is to design a therapy that will replace the missing enzyme through a single procedure and provide a long-term cure for the brain. We currently do this by modifying the patient’s own haematopoietic stem cells, which are the cells that differentiate into your blood and immune systems. Haematopoietic stem cells are extracted from the patient’s bone marrow, modified in the lab and re-infused into the patients. This process is known as a bone marrow transplant. 



During the first year of my PhD, I developed a lentiviral vector, which is a therapeutic virus derived from HIV-1, to carry the correct ‘version’ of the IDS gene. The lentivirus can be added to the haematopoietic stem cells in the lab, where the virus integrates into the genome and delivers the correct gene. This method allows haematopoietic stem cells to produce the right enzyme.

By correcting the cells and infusing them back into patients, we expect blood cells to be able to reduce the amount of complex sugar molecules that are stored throughout the body. Most importantly, we know that certain blood cells called monocytes can cross into the brain and have an impact there.

The rest of my PhD will involve evaluating this therapy in the mouse model of severe Hunter, where I analyse enzyme levels in the brain, sugar accumulation, neurodegeneration and behaviour 6 months after the transplant. Ultimately, we are hoping to put this through to clinical trials and get the therapy to Hunter patients as quickly as possible!

Going Further

If you’d like to know more about our research lab and the work that we do, visit our page: http://www.manchester.ac.uk/research/brian.bigger/research

If you are keen to know more about gene therapy in general, visit: http://www.bsgct.org/ or http://www.asgct.org/

For updates on MPS disorders in the UK, please visit: http://www.mpssociety.org.uk/en/

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