In this interview as part of the Early Career Innovators series, recognising the amazing translational work being done by postdocs and non-tenured researchers at University College London (UCL), Dr Annalucia Darbey and Dr Charlotte Spicer highlight their joint Cell and Gene Therapy Therapeutic Innovation Network (TIN) Pilot Data Fund awarded project, investigating the comparison of novel gene therapies to treat an inherited neurodegenerative disorder.
What is the title of your project and what does it involve?
Our project is entitled “Comparing novel AAV gene therapies for the treatment of Kennedy’s disease”.
Kennedy’s disease is a debilitating, inherited neurodegenerative disorder that primarily affects men, and is caused by a mutation in the androgen receptor gene. Patients initially develop painful muscle cramps and twitching which then progresses to weakness and wasting of muscles in the arms and legs. Muscles in the facial and bulbar region are also affected which can cause problems with swallowing and speech.
The goal of our research is to develop an adeno-associated virus (AAV)-based gene therapy that is capable of reducing levels of the toxic mutant androgen receptor protein, specifically in muscle. We are comparing three different technologies in vitro, which will allow us to determine the most effective and safest way of silencing the androgen receptor.
What is the motivation behind your project/therapeutic?
There remains no effective disease-modifying treatment for Kennedy’s disease, despite affecting up to 1 in 40,000 men, so there is a huge unmet clinical need. There has been substantial progress in the development of gene therapies in recent years and similar approaches have already shown success in preclinical trials of other neurological disorders. As all cases of Kennedy’s disease are caused by the same mutation, a successful gene therapy approach, targeting the androgen receptor would have a beneficial impact for all patients.
Can you highlight any challenges have you experienced as an early career researcher in the Cell and Gene Therapy/translational research space?
Annalucia Darbey: Relocating to a new university, particularly during a pandemic, was a challenge. It takes time to settle in a new research environment and build new relationships and collaborations.
Charlotte Spicer: Likewise, although I have been at UCL for a number of years now, I had limited experience in the gene therapy field when I started my current postdoc position, so there were many new things to learn!
We both feel very fortunate to be surrounded by such a strong network of scientists working on gene therapies and have fantastic support from our mentors Prof Pietro Fratta and Dr John Counsell. It’s also a great opportunity for us as basic scientists to gain a better understanding of downstream steps of the translational development pathway, such as the regulatory pathways and commercialisation.
Why did you want to apply to the Cell and Gene Therapy TIN Pilot Data Scheme?
The Cell and Gene Therapy TIN Pilot Data Scheme was the perfect funding opportunity for us. We are both early career researchers, working together on an innovative and highly translatable gene therapy project. As some parts of the project had already been funded, the Cell & Gene Therapy TIN Pilot Data Scheme has allowed us to independently explore an otherwise unfunded avenue of the project that, if successful, will allow us to apply for larger grants in the future.
How did you find the process for the TIN Pilot Data Scheme? What did you learn?
The overall process was very straightforward. The application for the TIN Pilot Data Scheme differed from other pilot data grant applications in that it was focused on the translational outcome of the project. By asking questions concerning the background IP and relating our idea to a product, we began to learn a lot more about what hurdles may need to be overcome further down the line when it comes to trying to get our therapy to patients.
We were both able to attend the ACCELERATE Pitching Skills training workshop prior to the Cell and Gene Therapy TIN Dragons’ Den panel. We found this incredibly useful and would advise any future candidates to take part in this training if possible.
What do you hope to achieve in the 6 months duration of your project?
In the 6-month duration of the project, we hope to generate enough pilot data to allow us to move our studies in vivo. Our ambitious long-term goal is to get our therapeutics into clinic, to provide the first disease-targeting treatment for people with Kennedy’s disease and possibly apply this technology to treat other similar genetic disorders in the future.
About Dr Annalucia Darbey
Dr Annalucia Darbey studied an undergraduate degree in Biology in Liverpool, before moving to Edinburgh to complete her PhD in Tissue Repair focusing on the development of gene therapy for the treatment of Endocrine Disorders. After a short postdoc continuing this research in Australia, Dr Darbey returned to the UK in 2021 to start her current postdoctoral position at UCL, investigating Gene Therapies for Motor Neuron and Neuromuscular Diseases.
Despite her initial training being in endocrine and reproductive biology, Dr Darbey’s keen interest in gene therapy has allowed her to move into the Neuromuscular field which she has found to be a new and exciting challenge!
About Dr Charlotte Spicer
Dr Charlotte Spicer is a postdoctoral researcher in Prof Linda Greensmith’s lab at the UCL Queen Square Institute of Neurology. Charlotte received a degree in Neuroscience from the University of Leeds in 2013, which included a year’s industrial experience with the London Pain Consortium at Imperial College London.
She then undertook her PhD, funded by the MRC Centre for Neuromuscular Diseases at UCL, which she was awarded in 2018. Her current research focus is on the development of muscle-specific therapies for the treatment of the Kennedy’s disease.