select search filters
briefings
roundups & rapid reactions
Fiona fox's blog
Scientists comment on top line results from a phase I/II trial of a gene therapy to slow the progression of Huntington’s disease.
Comment below from Professor William Gray who performed the gene therapy surgeries in the UK (not a third-party comment):
Professor William Gray, Professor of Neurosurgery and Director of the Advanced Neurotherapies Centre at Cardiff University, said:
“This is a landmark result for patients with this terrible disease and their families. We are delighted to have worked with Prof Rosser, here in Cardiff, and Profs Tabrizi and Wild in London to operate on their patients, delivering the gene therapy directly into the brain. Cardiff is the only UK centre – and only one of a few centres worldwide – performing these gene therapy surgeries. We wish to acknowledge the courage of our patients undergoing these experimental clinical trials, the work of Uniqure, and the fantastic clinical and research teams here in Cardiff making these therapies a reality.”
Prof Zosia Miedzybrodzka, Honorary Consultant Clinical Geneticist & Service Clinical Director- Genetics, NHS Grampian, and Co-chair at the Scottish Clinical Genomics Forum, and Professor of Medical Genetics, University of Aberdeen, said:
“This a very exciting and important breakthrough. However, it is still early days and a lot more testing is needed to see if there are side-effects of this new gene therapy, how long the benefits last and how well it works in the long term.
“The FDA is considering an accelerated testing programme, but I will take at least 5 years, and it will be much longer before long-term benefits and any side-effects can be fully assessed. Other drugs that reduce the effects of the HD protein are also being assessed.
“But this is a groundbreaking first step and a day to celebrate! “
Prof Siddharthan Chandran, Director of the UK Dementia Research Institute, said:
“This is incredible news for everyone affected by Huntington’s, a cruel and devastating disease. For the first time, we have a drug that slows down Huntington’s progression, with people on the treatment showing 75% slower disease progression over the 36-month study.
We’ll need to wait for the full peer-reviewed results to come out, but this is promising and gives real hope to families dealing with this disease. The next step is getting this drug into larger, late-stage trials.
I want to give my congratulations to the research team – this comes from decades of dedicated work by Professors Tabrizi, Wild and the whole team, not to mention the pivotal role of the families who have taken part in the research. Sarah, a Group Leader here at the UK Dementia Research Institute, has been instrumental in this breakthrough, and we’re very proud of her progress and contribution to this life-changing research.”
Prof David Rubinsztein, Professor of Molecular Neurogenetics and Deputy Director, Cambridge Institute for Medical Research, said:
“This is very promising news. Huntington’s disease is caused by a mutation that makes the huntingtin protein toxic to cells. Hence, reducing the levels of mutant huntingtin is a rational therapeutic strategy. uniQure have developed a way to accomplish this using a virus expresses an artificial microRNA that lowers huntingtin expression. The virus is administered into the brain. The early stage trial that they have reported involves a modest number of patients and much of the control data were not from placebo-controlled patients but from existing natural history data of Huntington’s disease patients. The results that were reported are from the high-dose group which comprised 17 patients, 12 who were followed up for 36 months. No data were reported from the low-dose group but the impression from the press release was that no significant benefits were seen with the low dose (which is fine if the high dose works and is well-tolerated). The analyses that have been reported are exciting as they suggest a clear slowing of disease progression measured with a range of tools along with a suggestion amelioration of neurodegeneration. While these headline results are from a press release and not from a publication where all the data and analyses can be seen, this provides real hope for this devastating disease. Importantly, this treatment strategy was generally well tolerated. This approach, if successfully validated has much broader implications as it may have potential to reducing the levels of other toxic proteins causing other dementias, forms of Parkinson’s disease and forms of motor neuron disease. This could be a major breakthrough.”
Prof Roger Barker, Professor of Clinical Neuroscience and Honorary Consultant Neurologist, University of Cambridge, said:
“The results are encouraging but it is early days and we have been here before with other similar therapies for Huntington’s disease [1]
“The trial involves injecting the therapy directly into the brain using a special technique into the striatum on each side of the brain- so its widespread adoption across neurological centres will not be straightforward if it is shown to truly work.
“The striatum is the area that has the greatest pathology in HD, which is why it was targeted in this trial and is known to mediate many but not all the features of HD and the data as reported shows improvements across a number of measures including a proxy marker of nerve cell loss called neurofilament light.
“Whether injections restricted to specific brain sites can slow down the disease across the whole brain is still unclear but the data from this trial is much better than anything we have seen before so this looks good- but currently does depend on brain surgery for delivery which is not without risk.”
Prof Paresh Malhotra, Professor of Clinical Neurology, Imperial College London, said:
“This announcement represents a potential major step in the treatment of Huntington’s Disease and Neurodegeneration more broadly. The treatment consists of a highly advanced approach involving neurosurgery and gene therapy, and it appears to have significant effects on disease slowing when treated patients were compared to a control group from another cohort of people with Huntington’s. This is a company announcement and the results have not yet been presented at a scientific conference or published in a journal, but they will bring hope to people affected by this devastating disease, and provide further evidence that better understanding of disease mechanisms will bring us closer to effective treatments.”
Prof Christopher Shaw, Professor of Neurology at King’s College London and Chief Scientific and Clinical Advisor for AviadoBio, said:
“UniQure’s gene therapy is the first to slow disease progression in Huntington’s disease. This is a fantastic result that exceeds expectations. A one-time brain injection of a safe virus engineered to carry a gene-silencing mini-gene prevents mutant HTT protein from poisoning brain cells. This is a world-first for viral gene-silencing in the brain and could be a treatment for life. If it is safe in the long-term and affordable then it could prevent people carrying the Huntington’s gene mutation from developing symptoms. This breakthrough opens the door to use viral vectors to treat other developmental and degenerative brain diseases.”
Declared interests
Prof David Rubinsztein: “David Rubinsztein is a consultant for Drishti Discoveries, PAQ Therapeutics, MindRank AI, Retro Biosciences, Alexion Pharma International Operations Limited, Carlyle Investment Management LLC, Aladdin Healthcare Technologies Ltd, Nido Biosciences, ProtosBio and is cofounder and Chief Biology officer of Acuity Technologies Ltd.”
Prof Paresh Malhotra: “I receive research funding from NIHR, MRC, Dementia Platforms UK, Alzheimer’s Research UK, the Football Association, British Heart Foundation and Alzheimer’s Society. I am a Trustee for Alzheimer’s Society, Group leader of the UK Dementia Research Institute, and am the National Specialty Lead for Dementia and Neurodegeneration in the NIHR Research Delivery Network. I have sat on on two NHS England policy working groups looking at diagnostic pathways and delivery issues relating to lecanemab treatment for Alzheimer’s Disease. I practise clinically at Imperial College Healthcare NHS Trust and also carry out a fortnightly private clinic at Cleveland Clinic London.”
Prof Christopher Shaw: “I have no connection to Uniqure. Consultancies and commercial funding to Shaw lab: AviadoBio, Avexis/Novartis, Biogen, Ionis, Eli Lilly, Quralis, Glaxo Smith Kline, Wave life Sciences. Employment compensation & stock: AviadoBio, Co-founder and Chief Scientific & Clinic Advisor”
Siddharthan Chandran: “Siddharthan is the academic lead of Neurii, a £5M partnership to deliver patient focused digital health solutions for dementia, part funded by Eisai. The UK Dementia Research Institute holds partnerships with charities (BHF, Alzheimer’s Research UK, Alzheimer’s Society, Parkinson’s UK and LifeArc), and industry (Lilly, Eisai, Astex, SPARC and Ono).”
Prof Roger Barker: No COIs
Professor William Gray “Professor of Neurosurgery and Director of the Advanced Neurotherapies Centre at Cardiff University, performed the gene therapy surgeries in the UK. The Advanced Neurotherapeutics Centre (ANTC), in close collaboration with the Cardiff and Vale University Health Board, is the only centre in the UK that can perform the surgeries included in the trial – directly delivering the gene therapy to the brain. “
For all other experts no reply to our request for DOIs was received.