Research
for the future of medicine
Fragile X
Click here to find our more about Fragile X syndrome
Leading Research
Part of Gene Works mission is to gain insight and understanding into genetic medical conditions. Our expertise is within intellectual disabilities but as it is believed that knowledge in one area of genetics will have useful application in others, we do not limit our research by condition but to follow where the science and discovery takes us!
At Gene Works we have a world class research team who bring together years of experience with the goal of helping to attenuate the symptoms of affected people with the ultimate goal of improving quality of life and striving towards as much independence in adulthood as possible. Not everything needs to be “cured” or being blinded by a one track mindset, which is why our team spend time with the people affected by the condition they are studying so they can see first-hand the challenges, behaviours and needs that their research looks to support. At Gene Works, we pride ourselves on a patient first approach to our holistic care solutions.
Why Fragile X?
To address the elephant in the room, our founder Chris McQuade has 2 sons who have Fragile X syndrome. This led to him being immersed in the world of intellectual disability, which in turn lead to hours of research into the condition, gaining understanding for the genetics and realising the huge lack of research, support and ultimately funding for Fragile X and wider to Neurodevelopmental conditions. This is where the drive to create Gene Works came from and some of the hypothesises, we work on today came from his research into Fragile X.
However, setting that elephant aside. Fragile X is really a perfect place to start as it is the number one cause of inherited intellectual disability in the world and affects all nationalities and races equally. Fragile X is also relatively simple, in medical terms, as it is one mutation on one chromosome that impact one gene (FRM1) which stops the production on one protein (FMRP). This gives us a detailed and focused place to target as well as a large community to work with and support.
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Our Research
CGG Repeats – A deep look
We wish to understand the relationship in CGG repeats in “Neurotypical”, Pre Mutation and Fragile X people. We will search for commonality in the sequence. Do we all have the same start, middle and end for example.
FMRP – But how quiet is it?
People with Fragile X Syndrome (FXS) are thought to have a silence of the FMR Protein. However Fragile X is a spectrum, as we see in autism, so is it not more logical that FRMP levels reduce with extended repeats rather than simple “on” before 200 CGG repeats and “off” after 200?
We will determine the level of FRMP present at different CGG repeats and if either specific CGG sequences stimulate FMRP or if the reduction of CGG repeats alters levels of FMRP.
To Activate or Deactivate – That is the question!
Two thirds of females with full Fragile X extension (FXS) show no symptoms where 100% of boys do. This is because females have two X chromosomes, one from Mum and one from Dad. Researchers from the University of California Los Angeles (UCLA) have observed higher levels of father to daughter X inactivation in autoimmune diseases. Our interest is in this relationship between mums X and dads X chromosomes and if we can find methylation regulators which will activate or deactivate one over the other. We will target these differences, if present, and therefore we may be able to activate the inactive X in stages and therefore unlock new treatment strategies.
FMRP, ASD and the Gene Works Project
Using our expertise and knowledge of the relationship with FMRP, we will look at the development of neural pathway and accumulate evidence for an association with Autism Spectrum Disorder (ASD) it has not yet been confirmed using common variants from genome-wide association studies but using our Gene Works Project, we hypothesis this will change as we look at the broadest ever spectrum of people with both methylated and unmethylated levels of FMRP.
One small edit for man…
Using cutting edge techniques such as Prime Editing using CRISPR and CAS variants we are exploring the possibilities of editing the FMR1 Gene to reduce the number of CGG repeats with a positive and manageable change effect. As Fragile X is a mutation and extension in the CGG repeats, understanding the CGG relationship in our “deep look” research will help us to understand if removing a repeat is necessary or if trimming the extension to introduce low levels of FMRP is possible. Our Gene Works Project is absolutely crucial and will allow us to compare Neurotypical and FXS FMR1 genes and the CGG repeat.
Nano Containers – Can they deliver a life-changing payload?
Investigating the use of nanosize containers that can slip inside cells and deliver protein-based medicines and gene therapies which are attached to CRISPR is an exciting and novel approach being developed by scientists at John Hopkins Medicine. We would like to investigate the potential of delivering FRMP via nano containers.
Fragile X seems well-suited for CRISPR gene therapy because it targets a specific type of cell. Other inherited diseases such as cystic fibrosis and muscular dystrophy may be more difficult to treat because they affect different cell types in different organs. Our research is not about discovering the editing techniques but about putting them into a practical and safe application using our extensive knowledge gained from the research you help to fund.
We are still a very early stage startup organisation.
Please feel free to get in touch and ask us anything.