Mona Eskandaripour meets Dr Sarah Tabrizi and discusses recent advances in gene therapy
We’ve all read it – or at least the BBC headline – “Huntington’s disease successfully treated for first time”. Coming from a neurosciences background, I was especially intrigued.
In my former degree(s), Huntington’s was usually lumped at the end of a neuro-degeneration lecture. Given its relatively well-understood aetiology, it didn’t occupy much lecture time or capture headlines like Alzheimer’s or Parkinson’s. This was why it was particularly exciting to read about how recent advancements are changing the way Huntington’s is talked about.
Dr. Sarah Tabrizi, Director of the UCL Huntington’s Disease Centre and a University of Edinburgh alumnus, is part of the research team that has accomplished this incredible feat. She spoke to me briefly about what this all means.
Huntington’s is genetic neurodegenerative disorder that typically presents at around 30 to 50 years of age with involuntary movements and is associated with dementia and psychiatric symptoms. With no disease-modifying therapies, its devastating impact on young adults was a significant driver for Dr. Tabrizi’s own personal interest and research into the condition. “It robbed young people of the ability to talk, swallow, communicate and walk,” she says.
New treatments
AMT-130 is a novel treatment injected into the brain over a 12-16 hour operation, silencing the mutant gene to prevent cell death. It is important to note that news outlets are not the most adept at accurately summarising medical research. However, these types of attention-grabbing medical headlines raise important questions for many stakeholders – patients, public, biotech industry, researchers, and especially, medical students. While the peer-reviewed findings are yet to be published, uniQure, the Dutch company responsible for producing this therapy, reports a 75% slowing of disease progression, as well as a significant slowing in motor and cognitive decline as compared to controls.
It was a result that surprised and excited Dr. Tabrizi, who understands the perseverance necessary in research. She says: “I’ve had to get used to seeing negative trial results and failures along the way. So when I saw these very positive results it was truly exciting!”
However, it will be some time before this treatment is readily available. There are currently only three gene therapies licensed for use in NHS England – Casgevy, Zolgensma, and Luxturna. Patients with ß-thalassemia or sickle cell, spinal muscular atrophy, and Leber congenital amaurosis, respectively, now have access to therapies that are close to or curative for these previously-incurable conditions.
Approval process
First, there is getting approval. Gene therapies generally come with risks like unintended immune activation and infections from viral vector-based therapies, as well as off-target changes to healthy cells, and errors in genes that precipitate cancer. While Casgevy has been approved by NHS England, it has been provisionally approved by NHS Scotland under the Ultra-Orphan Pathway, which allows for the use of novel medicines for rare diseases over a three-year period, contingent on further review that will dictate its routine use.
Then, there are the costs. Casgevy costs £1,651,000 per treatment, making it one of the most expensive therapies currently available. Biotech/pharma companies make deals with the NHS, providing undisclosed discounts on these medications that are funded through the Innovative Medicines Fund, but the cost-effectiveness analyses for these drugs will still preclude their immediate and widespread use.
So, incorporating new gene therapies into regular medical practice is a long, hurdled journey. As a student, gene therapies raise questions about the future of personalised medicine and how our practices will look one day. With a better understanding of what gene therapy could look like, now whenever I am reading up on some genetic condition (most recently Charcot-Marie-Tooth!), I can’t help but wonder whether one day soon, these too will be an “incurable” condition of the past – re-classified and taught like any other treatable disease. Perhaps every medical student once felt this way – seeing the technological advancements and medical achievements of their time put into practice just as they were on the cusp of joining the physician community.
It invokes a very fascinating and unpredictable future. Studies are being conducted looking at gene therapies for Alzheimer’s disease, Hunter syndrome, and paediatric hearing loss, to name a few. The disorders we learn about today, labelled idiopathic or incurable could very well be on the edge of new treatments. Could one of us be part of the research team that imagines, creates, and implements the next generation of gene therapies?
For Huntington’s disease and AMT-130, the clinical trial is still underway in the US, UK and Poland, as Dr. Tabrizi’s team works to gain MHRA approval for the therapy in the UK. But, as new techniques come into play, such as new viral vectors and small-molecule therapies, the costs, operation times and implementation hurdles could be overcome more quickly. Dr. Tabrizi’s team “are currently part way through a project with colleagues in the US which is looking at a viral vector with similar potency that can be delivered over just four hours of surgery.”
Remember, research is never over! This is the first step – a very important first step – into bringing relief to a significant population of individuals, and serves as a testament to the amazing research supporting a new wave of therapeutic approaches that will revolutionise medical practice in our lifetime. We just need to keep an eye on what the future holds!
Thanks to Dr. Tabrizi for sharing her valuable time, her expertise, and insight into this topic.
