Latest news with #AIPL1
Yahoo
05-03-2025
- Health
- Yahoo
Gene Therapy Partially Restores Sight in Legally Blind Children
A promising study out of the United Kingdom has partially restored the vision of multiple small children born legally blind. The experimental treatment uses gene therapy to resolve a retinal disorder called LCA4, which prevents the eye from distinguishing objects in a person's environment. Though limited, the study suggests that blindness caused by genetic defects could be curable. LCA4—short for leber congenital amaurosis-4—is caused by a series of mutations in the AIPL1 gene, which is responsible for the function and survival of the retina's photoreceptors. When AIPL1 is defective, the eye can't see; at best, a person can only see vague spots of light. People with LCA4 experience blindness from infancy, with some losing even the ability to perceive light as they age. Today, it appears gene therapy can help to restore at least some LCA4-related vision loss. In a study at University College London's Institute of Ophthalmology, researchers placed healthy copies of the AIPL1 gene within a virus engineered to target retinal cells without triggering actual illness. (This part isn't particularly new; engineered adeno-associated viruses have been used to deliver DNA to cellular targets for years now.) Once in the retinal cells, the "new" AIPL1 gene replaced the defective version, helping to slow the deterioration of the retina and even develop healthy photoreceptors. The study was published in the February issue of The Lancet. In an effort to protect and build upon LCA4 patients' extremely limited sight before it was too late, the researchers selected children ages 1 through 3, who experienced severe retinal dystrophy but could still perceive small amounts of light. Each of four children received an injection of healthy AIPL1 in one eye while under anesthesia. Then the team monitored the children's health and vision, conducting different light and color perception tests as the children aged. A child participant locates a small white object against a dark background after receiving gene therapy for LCA4. Credit: Michaelides et al, The Lancet/DOI 10.1016/S0140-6736(24)02812-5 All four children showed "meaningful responses" to the therapy—in fact, while vision improved remarkably in every treated eye, each untreated eye lost its ability to perceive light entirely. The children gained the ability to sort different-colored crayons into cups, follow a pen light, locate tiny white objects on a dark background, navigate a normally lit corridor, identify doors, and even draw. According to the researchers, the children have each moved from "legally blind" status to "low vision" status, amounting to a massive quality-of-life upgrade. Since the completion of this study, the researchers have begun working with a second cohort of seven children who have received treatment in both eyes. Results of this trial aren't quite ready yet, but they must be encouraging, as the team notes they are "exploring the feasibility of making the [treatment] more widely available."
Yahoo
24-02-2025
- Health
- Yahoo
MeiraGTx seeks UK approval after gene therapy restores sight in children born blind
MeiraGTx is advancing its investigational gene therapy toward expedited approval in the UK after 11 children who were born blind from birth gained significant vision improvements following treatment. The AAV-AIPL1 therapy is designed to address severe sight impairment caused by mutations in the AIPL1 gene. This condition is a form of retinal dystrophy that leads to severe visual impairment from birth, with affected individuals typically only able to distinguish between light and dark. The gene therapy involves injecting functional copies of the AIPL1 gene into the retina using an adeno-associated viral (AAV) vector, aiming to restore retinal cell function and prevent degeneration. Results from four of the 11 children were published in The Lancet on 21 February. The first four children treated were aged one to three years with severe retinal dystrophy linked to mutations in the AIPL1 gene. Each child received the therapy in one eye through subretinal injection. Outcome measures included visual acuity assessments, functional vision evaluations, visual evoked potentials, and retinal structure imaging. Before treatment, the children's visual acuity was limited to light perception. At an average follow-up of three and a half years post-treatment, the treated eyes showed significant improvement, with visual acuity improving. In contrast, the untreated eyes' visual acuity deteriorated to unmeasurable levels. Additionally, objective tests confirmed enhanced visual function and electrophysiological assessments indicated increased visual cortex activity specific to the treated eyes. Imaging revealed better preservation of retinal structure in treated eyes compared to untreated ones. MeiraGTx's CEO Alexandria Forbes said: 'These improvements extended outside the meaningful effects on vision and result in life-changing benefits in all areas of development including communication, behaviour, schooling, mood, psychological benefits and social integration.' Following these positive outcomes, a second cohort of seven children received treatment in both eyes. All 11 children treated with AAV-AIPL1 have so far exhibited meaningful visual improvements. One child experienced cystoid macular oedema in the treated eye, which partially improved over time and did not hinder the overall visual gains. No other significant safety concerns have been reported. In light of these findings, MeiraGTx has engaged in discussions with the UK's Medicines and Healthcare products Regulatory Agency (MHRA) and plans to submit AAV-AIPL1 for expedited approval. The company is also in talks with the US Food and Drug Administration (FDA) to explore accelerated approval pathways in the US. If approved, AAV-AIPL1 would be eligible for a priority review voucher (PRV). While gene therapies hold promise for rare diseases, commercialisation remains a challenge. High development costs, complex manufacturing processes, and limited patient populations often deter investment. Earlier this month, Italian charity Telethon Foundation submitted a marketing authorisation application (MAA) to the European Medicines Agency (EMA) for a gene therapy targeting Wiskott-Aldrich syndrome after the withdrawal of its commercial partner. This marks the second time the foundation has stepped in to support an abandoned gene therapy, following its efforts with simoladagene autotemcel for ADA-SCID. The foundation claims to be the first charity worldwide to take responsibility for drug production and distribution, highlighting the financial and logistical hurdles in bringing gene therapies to market. The incidence of AIPL1-associated severe retinal dystrophy is estimated to be around one in every million live births. During a call with investors, Forbes stated that the company is exploring all options to ensure global access to AAV-AIPL1, noting 'strategic interest' in the therapy. "MeiraGTx seeks UK approval after gene therapy restores sight in children born blind" was originally created and published by Pharmaceutical Technology, a GlobalData owned brand. The information on this site has been included in good faith for general informational purposes only. It is not intended to amount to advice on which you should rely, and we give no representation, warranty or guarantee, whether express or implied as to its accuracy or completeness. You must obtain professional or specialist advice before taking, or refraining from, any action on the basis of the content on our site. Sign in to access your portfolio
Telegraph
21-02-2025
- Health
- Telegraph
Watch: Blind children see for first time after British medical breakthrough
Children who were blind at birth can now see after British doctors successfully administered pioneering gene therapy in a world first. The 'spectacular' breakthrough at Moorfields Eye Hospital is the first effective treatment for the most severe form of childhood blindness. The children, who suffer from an extremely rare genetic condition, can now see shapes, find toys, recognise faces, and in some cases, can even read and write. The procedure, which takes around an hour, involves injecting healthy copies of the affected gene into the back of one eye to 'kick-start' sensitivity. Specialists hope the procedure can be made more widely available in the UK and elsewhere as a licensed treatment. The four children were picked by specialists from Moorfields and UCL Institute of Ophthalmology in 2020. All had severe retinal dystrophy known as leber congenital amaurosis (LCA), an inherited condition that causes vision loss due to a defect in the AIPL1 gene. This gene is important for the function of photoreceptors, light-sensing cells in the retina that convert light into electrical signals that the brain interprets as vision. 'Power of gene therapy to change lives' Prof Michel Michaelides, a consultant retinal specialist at Moorfields and professor of ophthalmology at the UCL Institute of Ophthalmology, said: 'We have, for the first time, an effective treatment for the most severe form of childhood blindness, and a potential paradigm shift to treatment at the earliest stages of the disease. 'The outcomes for these children are hugely impressive and show the power of gene therapy to change lives.' A research paper published in the Lancet has outlined the findings from the trial. Prof James Bainbridge, consultant retinal surgeon at Moorfields and professor of retinal studies at the UCL Institute of Ophthalmology, said those born with the condition could barely see from birth. 'Typically, they can only distinguish light and dark, and that little sight they will lose within the first few years of life. So what we found is that by providing the gene to their eyes that's otherwise lacking, we can substantially improve their sight, and this appears to have a positive impact on their general development.' The operations were carried out at Great Ormond Street Hospital in London, with medics performing keyhole surgery on patients aged between one and two to access the eye. Healthy copies of the AIPL1 gene, contained in a harmless virus, were then injected into the retina, the light-sensitive layer of tissue at the back of the eye. 'The effect of that is to kick-start, if you like, the sensitivity of the retina,' Prof Bainbridge said. 'The expectation is that that might have some benefit to their sight within a few weeks or months, and indeed we were delighted to see that that was indeed the case.' The gene therapy was only administered into one eye per patient to overcome any potential safety issues. Given the rarity of LCA, patients had to be found outside the UK, with families travelling to London from the US, Turkey and Tunisia. 'This particular condition is really very rare,' Prof Bainbridge said. 'And so we were able to extend the possibility of treatment globally, and the first families who approached us with children eligible happened to be from outside the UK.' The children were followed up over the next four years to determine the long-term effect of the therapy. Researchers used a number of ways to assess the children's sight, including reading letters and using scans of the eye to judge the preservation of cells in the retina. 'The parents were delighted, frankly, to see that the sight of the treated eye improved so substantially,' Prof Bainbridge said. 'They were very relieved and very positive about the findings. 'The parents describe the children gaining confidence in terms of their mobility, their independence, their ability to find their way around, also in terms of their recognition of shapes and faces and images. 'Some children are even able to read and write following the intervention which is something that one would absolutely not expect in this condition, untreated.' Brendan and DJ, who did not wish to share their surname, travelled from Connecticut in the US so their son, Jace, could have the treatment in September 2020. Jace was around two when he had the procedure. Jace's mother DJ said: 'After the operation, [he] was immediately spinning, dancing and making the nurses laugh. He started to respond to the TV and phone within a few weeks of surgery and, within six months, he could recognise and name his favourite cars from several metres away; it took his brain time, though, to process what he could now see. 'Sleep can be difficult for children with sight loss, but he falls asleep much more easily now, making bedtimes an enjoyable experience.' Jace's father, Brendan, said that the results were 'nothing short of spectacular'. Since the initial treatments were administered, a further seven patients have been treated at Evelina London Children's Hospital by specialists from St Thomas' Hospital, Great Ormond Street and Moorfields. They include Harvey Haines who struggled to interact with other children, before surgery, when he was three. His parents Jess and Brad said the operations had transformed his life – the previously withdrawn little boy now happily plays with his older sister and other children. His mother Jess, from Australia, said: 'That's really exciting to see, to see him building those friendships.' UCL developed the treatment using a manufacturer's special licence, granted by the Medicines and Healthcare Regulatory Agency (MHRA), which allows the production of unlicensed medicines for special clinical needs. It was supported by clinical stage gene therapy company MeiraGTx. Researchers said the new findings offer hope that children affected by both rare and more common forms of genetic blindness may in time also benefit from genetic medicine. The team is now exploring the means to make this new treatment more widely available. Prof Bainbridge said: 'The findings provide confidence that this particular approach can be helpful in even a severe condition. 'And of course, the hope is that the same approach might be helpful for children with more common conditions in the future. 'A similar gene therapy has been available for a similar form of genetic blindness on the NHS in the UK for some five years, but the findings of this particular treatment indicate that the same approach can work for a condition which is even more severe. 'The expectation and the hope is that that will be available to children for treatment in both eyes.'
The Guardian
20-02-2025
- Health
- The Guardian
Doctors in London cure blindness in children with rare condition
Doctors in London have become the first in the world to cure blindness in children born with a rare genetic condition using a pioneering gene therapy. The children had leber congenital amaurosis (LCA), a severe form of retinal dystrophy that causes vision loss due to a defect in the AIPL1 gene. Those affected are legally certified as blind from birth. But after doctors injected healthy copies of the gene into their eyes with keyhole surgery that took just 60 minutes, four children can now see shapes, find toys, recognise their parents' faces, and in some cases, even read and write. 'The outcomes for these children are hugely impressive and show the power of gene therapy to change lives,' said Prof Michel Michaelides, a consultant retinal specialist at Moorfields Eye hospital and professor of ophthalmology at the UCL Institute of Ophthalmology. 'We have, for the first time, an effective treatment for the most severe form of childhood blindness, and a potential paradigm shift to treatment at the earliest stages of the disease.' Four children aged between one and two from the US, Turkey and Tunisia were selected by specialists from Moorfields and UCL in 2020. The operations were carried out at London's Great Ormond Street hospital. Healthy copies of the AIPL1 gene, contained in a harmless virus, were injected into the retina, the light-sensitive layer of tissue at the back of the eye. The gene is vital for the function of photoreceptors, light-sensing cells in the retina that convert light into electrical signals that the brain interprets as vision. The therapy was only administered into one eye per patient to overcome any potential safety issues. The children were then followed up for five years. The results were published in the Lancet journal. Prof James Bainbridge, consultant retinal surgeon at Moorfields and professor of retinal studies at UCL Institute of Ophthalmology, said children born with LCA can distinguish only light and dark, and what little sight they do have they will lose within a few years. 'Some children are even able to read and write following the intervention which is something that one would absolutely not expect in this condition, untreated.' The parents of one of the children described the results as 'pretty amazing' and said they felt 'lucky' to have benefited. Their six-year-old son Jace, who was two when he was treated, can now pick tiny things up off the floor and identify toys at a distance. Brendan and DJ, who did not wish to share their surname, travelled from Connecticut in the US for the treatment in September 2020. 'Pre-surgery, at around two years old, you could have held up any object, even a couple of inches away from Jace's face, and he would not be able to track it,' said DJ. 'It didn't matter how bright it was, what colour it was, what shape it was. 'And now we get calls and notes home from school that he's stealing phones out of teachers' back pockets, which is hysterical to us.' Brendan said he noticed a difference within the first month when his son reacted to the sun shining through a window. 'He kind of pulled himself back. It wasn't just even an eye shut, it was more of a physical reaction. 'And I remember welling up and getting really emotional because that was the first time that Jace ever had any reaction to any sort of light stimulus or anything of the sort. From there, it's been pretty amazing.' UCL developed the treatment using a special licence granted by the Medicines and Healthcare Regulatory Agency (MHRA) and backed by gene therapy company MeiraGTx. Since the four children received the therapy, a further seven have been treated at Evelina London Children's Hospital by specialists from St Thomas' hospital, Great Ormond Street and Moorfields.
