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AADCd Induced Pluripotent Stem Cell (iPSC) Research


Professor Manju Kurian

The AADC enzyme is found inside brain cells that are called “neurons”. Neurons act as wires to move information around the brain. We know that in AADC deficiency some neurons do not work as they should do. This is because they do not make the neurotransmitters dopamine and serotonin. However we need a greater understanding of how AADC deficiency affects these neurons and how they respond to treatment.

One of the major challenges of investigating neurons in any disease is first obtaining the neurons to work with. As neurons are located within the brain they cannot be directly donated by patients. However there are many different types of cells and some of these such as skin cells can be more readily donated and used for medical research. Several AADCd families have very kindly donated skin cells for use in this project and we sincerely thank them for this.

Dr Manju Kurian and her team are using pioneering technology to turn AADCd patient skin cells called “fibroblasts” into neurons to use to investigate AADC deficiency. This complex process has two main stages. In the first stage, the skin cells will be reprogrammed into stem cells (technically known as induced pluripotent stem cells or iPSCs for short). Stem cells have the ability to become any cell type in the body through a process known as differentiation. In the second stage, neurons will be produced by differentiation of the stem cells using a defined chemical protocol. Throughout the process the cells will be rigorously checked to make sure they closely match those that would be found in the brain. The neurons produced in this way from AADCd patient skin cells will have AADC deficiency and so will be an exceptional resource for investigating the disease.

The Kurian laboratory will measure the amount and location of different proteins and chemicals involved in dopamine function including AADC; dopamine and metabolites; vitamin B6; and dopamine receptors that are the targets of dopamine agonist treatment in AADC deficiency. They will also undertake precise measurement of the amount of dopamine released from individual neurons following electrical stimulation. To look for new potential treatments the project will screen for chemicals that can improve the function of the AADC deficiency neurons.  Hopefully, this will lead to the discovery of candidate drugs or new drug targets that could drive forward novel treatment development. As well as this, the project will test gene therapy (see AADC gene therapy trials) in the neurons to gain an insight into the effects of this potential new treatment on individual cells. All together this project will provide fundamental knowledge of the subtle effects of AADC deficiency on individual neurons and hopefully provide new targets for treatment research.

The AADC Research Trust awarded 36,000 GBP towards this PhD Studentship supervised by Dr Manju Kurian at the UCL Institute of Child Health in London with the remaining costs met by a University College London (UCL) IMPACT Award. The project is due to be completed in 2018.

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A Patient Derived Dopaminergic Cell Model of AADCd Recapitulates Disease Phenotype and Reveals Key Mediators of Dopamine Dysregulation.

Poster created by Karolin Kramer

Utility of Induced Pluripotent Stem Cells for the Study and Treatment of Genetic Diseases : Focus on Childhood Neurological Disorders.

Authors : Prof. Manju Kurian & Serena Bassal (Research Associate) 2016

A word from the Founder & Managing Director, Lisa Flint, about the iSPCs project…

"It is not only a monumental moment when you can explain how a skin cell can be converted into a neuronal

cell, but more ground-breaking is, it actually may allow us to understand this disease at a far deeper-rooted

level than ever before.  Dr Manju Kurian, of Great Ormond Street Children’s Hospital in London, has an

unwavering interest in our disease and an absolute belief that we can create a stronger and healthier future,

with improved treatment strategies, for our children.  

We love working with Dr Kurian who is as passionate about AADC deficiency as we are.  We look forward to

a long continued relationship in this project and other future projects, including the impending Gene Therapy


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