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Heidelberg Engineering: Enhancing the Patient Journey

Clinical

1rem

Study results, including data from approximately 42,000 eyes, found diabetic retinopathy severity is a risk factor for diabetic eye disease progression. Other findings support the idea that genetic factors may influence the development of proliferative diabetic retinopathy versus diabetic macular oedema. 

Investigators find genetic factors may influence diabetic eye disease

Results of a study analysing cytokine levels in the aqueous humour and serum of patients with nonproliferative diabetic retinopathy with and without diabetic macular oedema support further research investigating transforming growth factor-β-induced Gene Human Clone 30 (BIGH3) as a potential biomarker for DMO.

Investigators explore pathogenic cytokines as biomarkers for DMO

In this roundtable, members of the Ophthalmology Times Europe® Editorial Advisory Board consider the top challenges and opportunities that they anticipate will affect ophthalmology in Europe in 2021.

Ophthalmic challenges in 2021: What to expect in the coming year

AMD treatment may become unrecognisable as gene therapies evolve

Starting from scratch on neovascular age-related macular degeneration

In a press release, the National Institute for Health and Care Excellence announced the first-ever approval for a mitochondrial disease treatment

NICE announces UK approval of idebenone for treatment of Leber hereditary optic neuropathy 

The Global RDH12 Alliance unites inherited retinal disease advocacy groups including UK-based Eyes on the Future and the US-based RDH12 Fund for Sight

Opus Genetics, Global RDH12 Alliance announce new collaboration

The platform, developed by University College London and Heidelberg Engineering, demonstrated accuracy and precision in early tests

AI-powered Eye2Gene uses multimodal imaging to diagnose inherited retinal disease

Insights from a genome-wide association study identify novel genetic loci

Unveiling genetic distinctions between reticular pseudodrusen and drusen

Omer Trivizki, MD, MBA, a retina specialist from Tel Aviv Medical Center, speaks about VOY-101, a Novel, Complement-Modulating Gene Therapy for Geographic Atrophy

Clinicians and industry partners continue the race to find the most efficacious therapy for 

. A new gene therapy may solve the puzzle for patients with non-neovascular AMD, and more information is coming soon from a Phase 2 trial, according to one retina researcher. Omer Trivizki, MD, MBA, a retina specialist from Tel Aviv Medical Center in Israel, shared details about VOY-101, a novel, 

complement-modulating gene therapy for geographic atrophy (GA).

The Eye Care Network caught up with Dr Trivizki at the 

American Society of Retina Specialists (ASRS)

 Annual Meeting in Long Beach, California. He explained the mechanisms beyind VOY-101( Perceive Biotherapeutics, Inc.) and the Phase 1 Beyond study (NCT06087458). 

"In our talk, we showed that VOY-101 is safe and tolerable," Dr Trivizki recounted. A 12-month survey of 24 enrolled patients showed there was no dose limiting toxicity, no systemic adverse effects and no ocular adverse effects, he said. "There was a really mild, transient intraocular cell effect that we observed during the study, which passed with topical steroids only, and eventually all patients were off steroids with no recurrence," Dr Trivizki said. "That led us to the conclusion that we can move ahead to the Phase 2 [trial] which...[dosed the first patient in late June]."

Dr Trivizki went on to explain the mechanism of the treatment, which is designed to provide patients with Complement Factor H gene (CFH) protection. "CFH protection is a protein that was found to 

," Dr Trivizki said. "The idea here is to provide, with one intravitreal injection, the protection effect of CFH...[and] to be able to use the eye as a production for this specific protein, so with a single injection, you can treat the patient for the long term."

Dr Trivizki explained that the Phase 1 trial had six sites across three countries, with most of the patients in Tel Aviv. The follow-up, Phase 2 trial, Journey, has started enrollment and dosing, and will follow patients to a 12-month primary endpoint, he added.

Videos

A 12-month follow-up indicated no dose limiting toxicity and no ocular or systemic adverse effects

First clinical results demonstrate efficacy of VOY-101, a novel gene therapy for GA

João Pedro Marques, MD, MSc, PhD discusses a retrospective study of 800 patients with inherited retinal diseases 

Gene therapies were a popular part of the programme during the American Society of Retina Specialists (ASRS) annual meeting. But even as clinicians understand more about genetics and inherited conditions, unsolved mysteries prevent patients from receiving vision-saving care.

At this year's ASRS meeting in Long Beach, California, the Eye Care Network spoke with João Pedro Marques, MD, MSc, PhD, about his presentation. He is affiliated with Centro Hospitalar e Universitário de Coimbra in Coimbra, Portugal. Prof Marques spoke about inherited retinal diseases (IRD) and common challenges in genetic testing. He explained that genetic testing can be a pain point for clinicians and patients, and obstacles to accurate testing can have a major impact on the care patients receive.

"Even if you use state-of-the-art genetic testing, up to 30% of patients will remain genetically unsolved," he said. These inconclusive outcomes can be highly frustrating, Prof Marques explained. As such, his team conducted a retrospective, single centre study. Its goal was to identify baseline determinants which might predict ifi a patient's IRD can be genetically "solved" and attributed to a specific gene function.

In the study, over 800 patients with IRDs were classified into predetermined phenotypes.

"We found that the age of onset [being] before 18 years of age, the presence of familial consanguinity and the presence of a family history are actually significant determinants to obtain a positive genetic testing result," Prof Marques recounted. "If you put these factors all together, the likelihood of obtaining a positive test is even higher. However, if none of these factors are present, you'll get only a 30% chance of having a positive genetic testing result."

"Our main highlight is actually how real-world data can impact your daily clinical practice," he continued. "This is very important because of access to clinical trials and access to new gene therapies. If you don't have a genetic diagnosis, you won't be able to be enrolled in these kinds of treatments."

Watch the video to hear the complete findings in this new IRD research.

Helping patients navigate the unsolved mysteries of genetic testing

At the Retina World Congress, we spoke with Siegfried Priglinger, MD, about ensuring the best outcomes for preschool-aged patients

At the Retina World Congress (RWC) in Fort Lauderdale, Florida, the Eye Care Network spoke with Siegfried Priglinger, MD. Prof Priglinger is director and chairman of the University Eye Hospital of the Ludwig-Maximilians-Universität, in Munich, Germany. The research he presented at the RWC focused on paediatric patients with inherited retinal diseases (IRDs), with an emphasis on studies into the RPE65 gene.

Prof Priglinger said that early intervention is key for ensuring the best outcomes for preschool-aged patients. One common IRD among this patient group is a defect of the RPE65 gene, which is responsible for activating photoreceptors in the retina. According to Prof Priglinger, it's up to general ophthalmologists to act fast when they suspect a patient may have a retinal disorder that requires specialist intervention.

"[General ophthalmologists] should always think of an IRD, and send patients to a specialist, to make sure these kids are recognised very soon," he urged. He went on to say that developing visual acuity is vital, and feasible for many young patients, who could experience protection or restoration of vision early on in their academic careers—a key indicator of long-term positive outcomes. "They can read and go to school, and just have a normal life," Prof Priglinger said.

He also noted that the world of gene therapy is expanding at an extraordinary rate, which could lead to an exponential increase in the number of therapies available. "What I would love is to have a treatment for every gene defect. It took more than 20 years for RPE65," he said. "Hopefully it's not going to take 25 years for each gene defect, but I'm pretty sure that researchers are going to solve this problem."

Early intervention is crucial for long-term outcomes in paediatric gene therapy

Alfredo Sadun, MD, PhD, chief of Ophthalmology at the Doheny Eye Institute, University of California Los Angeles, shared exciting new research with the Eye Care Network during the Association for Research in Vision and Ophthalmology (ARVO) meeting on the subject of Leber hereditary optic neuropathy (LHON).

Alfredo Sadun, MD, PhD, chief of Ophthalmology at the Doheny Eye Institute, University of California Los Angeles, shared some exciting new research with the Eye Care Network during the Association for Research in Vision and Ophthalmology (ARVO) meeting.

In Salt Lake City, Utah, Prof Sadun detailed a recent project examining Leber hereditary optic neuropathy (LHON). When the research produced an unexpected result, Prof Sadun said, it opened new possibilities for adeno-associated virus (AAV) delivery of gene therapies.

Editor's note: The below transcript has been lightly edited for clarity.

I'm a neuro-ophthalmologist with a great interest in one particular disease, which is Leber hereditary optic neuropathy. This is a genetic disease where you do just fine until you turn 20 or so, and then you suddenly go blind, first in one and then the other eye, very dramatically and very unfortunately. So we've been doing research together with GeneSight from Paris, France, for gene therapy for this disease. In doing so, we have found out that, at least in some patients, an injection of the gene via AAV2 intravitreally can lead to some improvement. 

This trial both succeeded and failed, enormously, because of the same phenomena. An injection in one eye somehow mysteriously caused improvement of vision in both eyes. This was a failure in the sense that, the FDA said, "You get approval if you can show the injected eye does much better than the other eye," but they both got much better. So they are not on the way for approval, as of right now. 

But the amazing thing is that they got more bang for the buck. Both eyes got better. The agency, GeneSight, thought this is because the virus went into the brain and came back down via the other optic nerve. I have a PhD in ocular anatomy, and said that didn't sound very likely. 

So we've been doing these investigations where—fortunately for us, but very unfortunately for the families—not one, but two patients who had undergone gene therapy died. And we had an opportunity of analysing the eye. In looking for products of the of the virus and of the transfer gene, we were able to find that it 

 in the other eye. So in this sense, the company was correct. 

But the concentrations of the virus did not get weaker. As you went back from the uninvolved eye, they got greater; meaning it got to the eye and then diffused back to the brain, not that it got to the injected eye, to the brain, and diffused forward into the eye. So we're still not sure how it got from one eye to the other, but it does not seem to be via the brain. 

Point number one is that we have misunderstood the directions of these vectors and how the infection leads to transfer. And so clearly, in [LHON], not only does this tell us a lot about treatment of that disease, but it tells us about AAV2 virus being a different story than we thought, which will apply to [Leber congenital amaurosis, LCA] and other diseases that might be using gene therapy for treatment. 

The other thing...it's going to be a fantastic opportunity when we finally understand how it works, but there are a lot of limitations. In LCA, they found out that it works really well in the short-term, but there's some decay of the effect, perhaps because we're putting in a good variant of the gene, but the old variant is still around, and they're in competition with each other. Somehow, when you have competition, usually the native protein wins. 

There are a lot of other issues at play here. [LHON] tends to affect people in their late teens and mid-20s. It's very sad, because people who expected to have their plans in their lives that have been interrupted enormously and shockingly and quickly. Most of our patients for the gene therapy trial were, therefore, in their early 20s. We only looked at patients who had lost vision within the last year, hoping that it was still salvageable, because the longer you wait after that, the optic atrophy would have put a ceiling on how much improvement we could have gotten. That's the nature of the disease. That's the nature of our experiments, the nature of when the gene therapy would work. But there is something that comes out of that which is unexpected, also. 

We initially started with 2 different groups: 0 to 6 months after loss of vision and 6 to 12 months. The 6 to 12 month group was plan B. [Our team was] thinking we're going to miss some of these patients because the diagnosis doesn't occur that quickly, since there are not too many neuro-ophalmologists around.

We expected the results to be much better in the 0 to 6 months [since diagnosis] group, because the optic atrophy had not really developed. There were more salvageable cells. 

To our shock, the 6 to 12 months patients did better than 0 to 6. Furthermore, when we did a subgroup analysis, amongst the 0 to 6, the only ones who did well were those who lost vision 5 or 6 months before the injection. And amongst the 6 to 12, the ones who did best were the ones around 11 to 12 months. 

So later is better. That's such a shocking thing that we went back and looked at the literature...for a medical treatment with an agent called idibenone, amongst the same patients. And it's not published yet, but I'm working on a paper that's entitled, "Later is better."

What we're looking at [next] is other tissues. We're looking at vascular tissues, lymphatic tissues. I mean, it's just a wild guess. I don't mean to suggest that I have a deeper insight than anyone else, but I think that maybe the glymphatics, the fluid, the [cerebrospinal fluid, CSF] around the brain, not the brain itself, might have been the conduit for this. In which case, you would expect it to sort of mix throughout the brain, to concentrate in areas that are the cul-de-sac of the CSF flow. The biggest cul de sac is the optic nerve head, just at the juncture of the optic nerve in the retina. So, that gradient we saw, which was highest there and going down further back, would make sense.

At the 2025 ARVO annual meeting, Prof Sadun shared an exciting update in our understanding of Leber hereditary optic neuropathy

ARVO 2025: Alfredo Sadun, MD, PhD, says "later is better" for some LHON interventions

Arun Upadhyay, PhD, discusses new study findings from Ocugen’s OCU400 trials

We live in an era of unprecedented progress in novel ocular treatments, including gene and cell therapies. Groundbreaking treatments are giving patients hope about vision-threatening diseases. If you speak with Arun Upadhyay, PhD, though, you'll see that the last few decades of progress are just the beginning, especially in the area of retina care.

Dr Upadhyay, who is the Chief Scientific Officer at Ocugen, sat down with 

 to explain ongoing trials of OCU400, a modifier gene therapy product candidate targeting retinitis pigmentosa. Here, he speaks about a gene-agnostic approach to retinal disease, and explains why age-related macular degeneration, Stargardt disease and other conditions may not be as simple as we think.

Hi. My name is Hattie, and I'm the editor of Ophthalmology Times Europe. Joining me today, I have Dr Arun Upadhyay. Dr Upadhyay, thank you so much for sitting down with me. I'm so excited to talk to you about gene therapy and what's going on at Ocugen.

 Thank you so much. We attended the EURETINA 2024 meeting, and in that meeting we presented data related to the OCU400 Phase I/II study for retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA)disease. And also, we talked about our ongoing OCU400 Phase III study design. For OCU400, we started with the Phase I/II study for retinitis pigmentosa and Leber congenital amaurosis. In the retinitis pigmentosa part of the study, we enrolled a total of 18 subjects distributed into Phase I and Phase II…Phase I was a dose escalation study, 3+3 design, and Phase II was our expansion phase, where we enrolled additional [RP] subjects who received high doses of the product. During the Phase II portion of the study, we also expanded this trial into the Leber congenital amaurosis patients, and in that arm, we dosed adult patients as well as paediatric patients.

The Phase I/II study, basically, was the basis for us in advancing to the Phase III clinical study. In the Phase I/II, OCU400 was generally safe and well tolerated. We had a very good safety profile. In addition, we also looked at the exploratory efficacy data from those patients. In the RP patient population, we saw many patients responding [to] various functional vision parameters such as mobility, best corrected visual acuity, and low luminescence visual acuity [LLVA]. And the majority of patients responded either, you know, showing the stabilisation of the disease or improvement on those parameters.

So, our ongoing Phase III study is basically focused on the retinitis pigmentosa patient, and in this trial, we have total of 150 patients who will be taking part in this study, distributed [equally] into two arms, the rhodopsin arm and gene-agnostic arm. And in each arm, these 75 patients will be further randomised in a 2-to-1 ratio, to either receive the OCU400 product or remain as an untreated control. This phase of study will consist of only one dose level, so just a single-dose study, and it involves both paediatric as well as adult participants. And as you know, this is the subretinal procedure, so injection is in the subretinal route. The primary endpoint for this study is going to be mobility, what we call LDNA, luminance dependent navigation assessment. And in this primary endpoint, basically we are looking at change in the Lux level from the baseline, up to12 months of the follow-up visit. So the way we are defining “responders” on this primary endpoint is, any patient who received the treatment and showed the improvement of two Lux or more on this mobility course will be defined as a responder. The criteria for meeting the primary endpoint [is] comparing the responders in the treatment arm versus the untreated controls.

 What's the philosophy behind a gene-agnostic therapeutic approach, for those who aren't as familiar?

 Very good question. So, if you look at the inherited retinal disease space as such, as you know, there are now more than 300 genes known to cause inherited retinal disorders. If you look at RP, there are close to 100 genes involved [which contribute] to this disease condition. So, from a disease perspective, retinitis pigmentosa has highly heterogeneous stages, when you look at whether a clinical or genetic cause. And one of the biggest challenges in this space is that there are some mutations which are rare in nature, but there are many mutations which are 

-rare in nature, and the patient population is not that large.

So, when we look at the traditional gene therapy approach, which is either gene augmentation or gene editing, though they have potential to fix certain gene genetic defects, when you look at the overall clinical development landscape so far, after Luxturna [voretigene neparvovec-rzyl, Spark Therapeutics], we don't have any products approved in this space. Not only that, if you look at the kind of pipeline we have in this space, it is still targeting only few sets of mutation using those approaches. And still, we are not seeing much success, and the reason for that is that when you look at the disease pathophysiology, these diseases are not as simple as we have been thinking. It is very complex in nature…Even though they are genetic disease, [genetics are] not the only factor which really determines the onset of disease, severity of disease or progression of the disease. There are other factors which contribute to the overall pathogenesis, clinical symptoms, manifestation and how disease is going to impact a patient. It is not just genetic mutation.

What we’ve learned that there is something more going on, and, what, exactly, happens? What 

 happens in this disease which leads to the vision loss? It is basically degeneration of the photoreceptors. So if we can find a way to preserve the photoreceptors, and enhance the function of existing photoreceptors, then there is a way that we may be able to provide benefit to the larger group of patients in this space. That is where our gene-agnostic, modifier gene therapy concept comes into the picture.

So in our pre-clinical development and early discovery studies by our inventor, Dr Neena Haider, we learned that there are groups of genes which belong to the nuclear hormone receptor class. They are nothing but a transcription factor. They are a regulatory molecule. They regulate various pathways in the retina which are crucial for maintaining the health of the retina, as well as the function of retina. What we noticed is that, in the animal models, irrespective of their genetic mutations…there was suppression of some key transcription factors or key regulators. Some of those key regulators were nuclear hormone receptor genes, and 

, or OCU400, was one of them. So when these animals were given OCU400, what we observed is that it brought back the level of all those suppressed, downregulated, master regulator genes to the normal physiological level. That is what mechanism of action is around.

Our gene agnostic approach is more like, you know, delivering a molecule, OCU400, which can bring homeostasis in the altered cellular and molecular pathway within the retina, which are crucial to preserve the function and structure of the photoreceptors. And by doing so, we will be able to…halt the progression of disease, or maybe even in some situations, [see] reversal in the functional part, based on what we are seeing in our Phase I/II study. Visual acuity gain in LLVA, and an improvement in vision on the mobility course. So that's what our larger gene agnostic approach is, and it has potential to provide benefit to the broader group of RP patients, irrespective of patients’ genetic backgrounds.

 Speaking really broadly about gene therapy, what are some of the biggest opportunities and what are some of the biggest challenges?

 So first I'll just look at the developmental challenges, and then the potential of this gene therapy approach. If you look at the developmental challenges, of course, gene therapy products are complex biologics, you know. So if you look at the evolution of the different classes of medicine, we started with a small molecule, then biologics, and then we have a gene therapy product. And this evolution…from a development perspective, you know, the Chemistry, Manufacturing, and Controls [CMC] quality, controlling the critical quality attributes, targeting and formulation stability, all those things are the areas which challenge [investigators], because if we are addressing only the rare disease space, then we don't see that as a bigger challenge. But still, that is a significant challenge when we start diversifying this gene therapy technology to other disease areas, or larger disease areas, where the product demand is very high. Those could be developmental challenges we may face.

But when I look at the potential of the gene therapy…look at, traditionally, when we started gene therapy, the goal was to fix something which is defective, by supplying either the normal copy of that defective gene, or finding a way to fix the defective gene within the cell, tissue or organ which is affected. And that's great, but now we have started exploring whether we can use a gene therapy in the place of earlier biologics, like mAbs or other factors. Rather than delivering protein, can we use a gene therapy approach to deliver the same molecule, using our own system as a biological factory? One of the biggest challenges is regulation. How we are going to control the level of that molecule [inside cells]? How we are going to make sure that that those bio factories which are inside, 

 bio factories, how they are going to control the level of those molecules, when we are taking the gene therapy approach? So I see there is a lot of promise for gene therapy. It is not just addressing the individual genetic defect or mutation, but also utilising this technology to address more complex diseases. Where genes can be used to deliver a factor or molecule, which addresses the complex cellular, [and] molecular pathway within the body.

 This therapy product is, is based on, as you said, 

, and that is kind of associated with a lot of different functions in the retina. Is that something that broadens the scope of applications, outcomes or patients who could benefit from these gene therapy candidates?

 As we started learning about modifier genes within the retina, we realized it is not just 

, but there are other set of genes which play similar kinds of roles, but in different disease conditions.

One of the modifier genes which we identified is RORA. We have another product candidate based on that RORA modifier gene, and we have two programmes ongoing using that product. We have OCU410, which we are developing for geographic atrophy, and we have another programme, OCU410ST, that is for the treatment of Stargardt disease. When you look at geographic atrophy, I think briefly I touched about the complexity of these diseases. And similar [complexities] apply for this other retinal disease that is geographic atrophy. We have made significant progress in this space and are trying to find a therapy which may provide a benefit to these patients. But still, we are not able to find a therapeutic which really, really can provide, what you call good benefits to these geographic atrophy patients. One of the biggest hurdles has been the disease itself. This disease is also multifactorial in nature. It's a very complex disease which [involves] genetic factors, environmental factors, and aging, as we talk about age-related macular degeneration. Pinpointing a single target in this disease has become very challenging, and a lot of development, if you look [at geographic atrophy treatments industry-wide], has been primarily focused on targeting a single target. When you are trying to address a multifactorial disease, where you know causes are diverse in nature and complex in nature, targeting one single pathway may not be the efficient way to provide the optimal benefit to these patients.

So that is where this gene-agnostic, multifactorial modifier gene therapy RORA molecule provides hope. When we did the pre-clinical study using this RORA molecule in the macular degeneration animal model and other various in vitro cell culture-based models, we observed that it is not just only one pathway, but this molecule targets multiple pathways linked to the pathophysiology of geographic atrophy. For example, not only just complements which [we in the field] have been targeting, many companies have been in this space, targeting that particular pathway. But also, it regulates the proinflammatory pathways, which are basically inducers for the disease. Targeting oxidative pathways, and the pathways which are linked to lipid peroxidation and modification, which eventually lead to the lipid deposits in GA, what we call drusen. So RORA targets all three pathways at the same time, multiple pathways at the same time. We believe that taking this multifactorial approach for the multifactorial disease is the right way to go. Right now, with this [OCU410] programme, we are in Phase II. We completed Phase I portion of the study…We are hoping to provide some safety and efficacy updates to the market sometime in near future.

Coming back to Stargardt disease. It's an ABCA4 gene mutation disease, and there is no treatment available for Stargardt. So the same molecule, because Stargardt, if you look at the disease pathophysiology and degeneration pattern for Stargardt, is similar to GA. Of course…there are some differentiations, but again, lipid deposits, what we call lipofuscin, and complements also play a role in Stargardt disease. So, in that animal model, we saw good efficacy, for RORA, in controlling lesion growth and drusen deposits, and upregulating the anti-complement protein. This programme is also in Phase I/II clinical development. We completed the Phase I portion of that study as well, and we are hoping to provide updates to the market sometime soon about preliminary safety and efficacy data.

 It sounds like it's been a really big year for you, and [Ocugen] also hit some regulatory milestones. Do you want to talk a little bit more about what you've been celebrating?

 Yeah, that’s great, actually. I think this year has been very remarkable for us in terms of regulatory milestones, especially for our gene therapy programmes. So to start with, the two major things I consider we achieved, from a regulatory perspective, was getting the FDA approval to initiate our Phase III study. In addition, we received alignment from the EMA for a marketing authorisation application, so we [aren’t] required to do an additional Phase III study to get approval of this product in the European market. So that was a huge achievement.

In addition to that, OCU400 has also received orphan drug designation from both the FDA and EMA for broader RP and LCA disease, it's not mutation specific. And we also received the Regenerative Medicine Advanced Therapy [RMAT] designation from FDA. It's given to the company or product which has shown some clinical benefit to the patient.

We also received [FDA approval for] an Expanded Access programme for the treatment of RP patients with OCU400. A few things which it highlights about the product: This indicates that the product has shown sufficient evidence of the safety and efficacy, which gives regulators confidence to allow the use of this product outside the clinical study protocol. RP is [associated with] significant unmet medical needs. So there will be patients who may not be able to meet some of the inclusion/exclusion criteria [in the ongoing phase 3 study]. And if those patients are willing to take this product, they can get this product, through the Expanded Access Programme. In addition to that, I would like to update you that we are already in a Phase III study. We are planning to complete the Phase III enrollment by sometime early next year, and we are targeting to submit the Biological License Application (BLA) and marketing authorisation application in 2026.

Arun Upadhyay, PhD, discusses new study findings from trials of OCU400 (Ocugen)

How a gene-agnostic approach opens doors to new therapeutics

Hoda Shamsnajafabadi, MSc, PhD, presents at the 2024 EURETINA Congress

 was privileged to speak with Hoda Shamsnajafabadi, MSc, PhD, who presented research which received the second-place prize for best e-poster (August Deutman award). Shamsnajafabadi is a postdoctoral research scientist at the University of Oxford, Oxfordshire, England.

The poster, titled "CRISPR-Cas mediated base editing approaches for CRB1 related retinal dystrophy," presents three case studies of patients with CRB1-associated retinal dystrophy. According to Shamsnajafabadi and her colleagues

 three pathogenic CRB1 variants, including a novel c.2833G>A variant, were found to be associated with early-onset cone-rod dystrophy. These findings further suggest that adenine base editors could be a suitable therapeutic approach for all three variants, and the topic warrants further study. The full abstract is 

The below transcript has been condensed and lightly edited for clarity.

: Hi, I'm Hoda, a postdoctoral scientist from Oxford University. I'm very pleased to get invited to EURETINA 2024. I was awarded the August Deutman prize because of the presentation that I brought here. It was about the CRISPR approach for treatment of CRB1-related retinal dystrophy.

Overall, I presented three case reports of CRB1, with early-onset cone-rod dystrophy. We offer CRISPR-based editing as an approach for the treatment of CRB1 diseases for further study. The process of selection of the patients for CRISPR studies is time-consuming. We need to develop new tools to reduce that time, make it faster, and to find a way for editing the variants, making it easier, faster and possible on a larger scale. I hope that, from my presentation, people have a few of how CRISPR editing could edit variants in future studies.


One thing I will remember about this conference is that all of our research group are here. I have a very nice memory of this because all of us support each other, and when I presented, all of them were in my presentation, even my Professor, Robert MacLaren. It was very nice. I was very emotional that all found the time for me and supported me that much.

The e-poster came in 2nd place for the August Deutman award at the EURETINA Congress

EURETINA 2024: CRISPR-Cas mediated base editing approaches for CRB1 related retinal dystrophy

Rich Small, CEO of Neurotech Pharmaceuticals, at ASCRS 2024

At the 2024 ASCRS meeting in Boston, Massachusetts, the Ophthalmology Times Europe team caught up with Rich Small, CEO of Neurotech Pharmaceuticals. Here's what he had to share with us, including an exciting preview of upcoming developments for NT-501.

Editor's note: This transcript has been lightly edited for clarity.

Hi, I'm Rich Small, CEO of Neurotech Pharmaceuticals. We already have a very novel technology we call encapsulated cell therapy [ECT], which consists of genetically-modified cells that are designed to release therapeutic factors over a sustained period of time into the back of the eye. Our most advanced ECT product is called NT-501, which releases a neurotrophic factor, CNTF. And we've been studying CNTF for an orphan disease called macular telangiectasia, or MacTel. 

We have completed our Phase III studies with very positive results, showing slowing down progression of disease over a 2-year period of time. Also at Neurotech, we've been putting our final touches on preparing to submit to the [US] FDA our biological license application. We are hopefully to submit it shortly. As well, we are creating and growing our infrastructure. So we recently have built out our commercial team. We've added to our clinical and medical affairs team. And we also are planning to manufacture our product for commercialisation, hopefully, once we get through approval. So all in all, a lot of exciting things going on in Neurotech. We're very excited and we will be keeping you updated as we make progress over the coming months. Thank you very much.

Rich Small, CEO of Neurotech Pharmaceuticals, provides an update on the months ahead for NT-501 encapsulated cell therapy

ASCRS 2024: New Phase III study results and near-future plans for Neurotech and NT-501 

Dr Carel Hoyng discusses his presentation at the Angiogenesis, Exudation and Degeneration meeting hosted by Basom Palmer. Entitled “Stargardt Disease, Towards Therapy,” Dr. Hoyng’s presentation explored the origins of Stargardt disease, proper diagnosis, current gene therapy trials and RNA therapy options.

Thank you for joining me today, Professor Hoyng, to discuss your presentation at the upcoming Angiogenesis meeting. Firstly, what are the main takeaway points from your upcoming presentation?

The main takeaway points from my presentation are that Stargardt's disease is the most common inherited retinal disease caused by a single gene. However, due to the difficulties of this gene—it's very large, it doesn't fit into an AAV virus—gene therapy until now, has not been undertaken at this moment. No trials in gene therapy.

There are a few trials that have a pharmacological approach by, for example, slowing down the visual cycle, which has a lot of times possible side effects. And we have undertaken now the efforts to make an RNA therapy, which is now called in United States ASO, antisense oligonucleotide, therapy to—with small molecules to repair the RNA. We are now in preclinical phase of research.

That's very interesting and how might the topics from your presentation be applied day to day?

One topic—subtopic—of my presentation, but very important, is that a lot of Stargardt's disease are not recognized properly.

So we know that the traditional picture of Stargardt's disease by a flecked retina and in children, but there is a part of Stargardt's disease that occurs in adults and is not recognized properly always. And is diagnosed mostly as dry AMD, which it is not. It's Stargardt's disease, and we have solved nearly all the genetic mutations in these patients.

So about 1/3 of patients with Stargardt’s disease are late-onset Stargardt's disease and should be recognized as that.

 What are the next steps for this research?

 In our research in where we try to repair the RNA mutations, the next step is that we will go into clinical Phase 1/2, and probably in about a year. And so that are the next steps at this moment. We are in talk studies. And the next step is to go to in-patients.

That's excellent. And finally, what are you most excited about in this field?

 In the total field of inherited disease, I am very excited that therapies are really coming on the market now. So all these kids that get blind by all different kinds of inherited retinal diseases. Now, in the near future, there will be therapies. And that's very exciting. I think one of the most exciting fields at this moment in ophthalmology.

 Indeed. Well thank you very much for that short interview. It was most interesting.

This transcript has been lightly edited for clarity.

Dr Carel Hoyng divulges the main takeaways from his Angiogenesis presentation, including the origins of Stargardt disease, correct diagnosis, ongoing gene therapy trials and the future of therapy.

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