“Taken together, we show that a defined class of compounds for RD treatment in combination with an innovative drug delivery method may enable a single type of treatment to address genetically divergent RD-type diseases.”
PTC124, now known as Ataluren, shows promise for the most common mutation that causes Usher 1C. Usher 1F is also caused by a nonsense mutation, and our researchers have begun testing the drug on our animal models.
“Three blind mice could be a thing of the past. Scientists have restored the sight of blind mice by implanting tiny gold prosthetic photoreceptors into their eyes. So far, this incredible technique has only been carried out on mice. However, the work holds some hope for people with degenerative eye diseases such as retinitis pigmentosa or macular degeneration….The beauty of this technique is that it doesn’t require additional micro-electronic gadgets to do its job, unlike most other current eye prosthetics.”
Treatment for Inherited Blindness – Exciting because it is not mutation specific
“Veterinary vision scientists at the University of Pennsylvania have safely and successfully used a viral vector in targeting a class of photoreceptors of the retina called rods, a critical first step in developing gene therapies for inherited blindness caused by rod degeneration.”
More exciting retinal gene therapy coming out of the University of Pennsylvania, this time not mutation specific and so relevant to all types of RP
“In what is promising to be a path-breaking work, the Japanese scientists led by Takashashi from the Laboratory for Retinal Regeneration, RIKEN Centre for Developmental Biology, Kobe have made progress in regenerating new neurons in damaged retina and transplanting new one’s from outside to tackle retinal problems.”An implant is in the works that could restore vision to those with degenerative retinal diseases. Unlike other implants seeking to do the same thing, this one could do so without the need for external hardware or complicated surgery and could potentially offer greater resolution for truly functional vision. The implant being developed by LambdaVision (Farmington, Connecticut), which is in preclinical stages, relies on a light-activated protein to bypass dysfunctional retinal cells.”
“In genome-editing, the challenge for CRISPR-wielding scientists is to edit only one of the two copies, or alleles, of every gene that people have, repairing the ever-so-slightly broken one and leaving the healthy one alone.
“Now, in one of the first research papers scheduled for publication in the first journal dedicated to research on CRISPR, scientists in Boston report “allele specific” editing of a gene that, when mutated, destroys the eye’s photoreceptors and causes the form of blindness called retinitis pigmentosa.”
“GenSight Biologics (Paris:SIGHT) (Euronext: SIGHT, ISIN: FR0013183985, PEA-PME eligible), a biopharma company focused on discovering and developing innovative gene therapies for retinal neurodegenerative diseases and central nervous system disorders, announced UK Medicines and Healthcare Regulatory Agency (MHRA) acceptance of the Company’s Clinical Trial Application (CTA) to initiate the PIONEER Phase I/II study of GS030 in patients with Retinitis Pigmentosa (RP).
“PIONEER is a first-in-man, multi-center, open label dose-escalation study to evaluate the safety and tolerability of GS030 in subjects with Retinitis Pigmentosa. GS030 is the combination of a gene therapy (GS030-DP) administered via a single intravitreal injection and a wearable optronic visual stimulation device (GS030-MD).”
“After 13 weeks of observation, the scientists noted that the rats having been transplanted with a patch showed the best visual performance, and over a longer time-frame, relative to the animals having received the suspended cells.
“On the strength of these results, in the coming weeks, the scientists will be submitting an authorization application for a phase I/II clinical trial in approximately twelve patients with retinitis pigmentosa, which is thus expected to start in about a year’s time, at Hôpital des Quinze-Vingts, under the supervision of Professor José-Alain Sahel. This will be the first cell therapy trial in the field of vision disorders, in France.”
“A new ‘checkpoint’ model which can be used to identify potential treatments for genetic disorders such as cystic fibrosis and Duchenne muscular dystrophy (DMD) has been proposed by a team of Bradford scientists. These disorders can be caused by a particular type of mutation in DNA, called a ‘nonsense mutation’. … The research team at the University of Bradford has come up with a new model that can be used to develop screening tests for both genes and chemical compounds, published in the journal Human Molecular Genetics. They believe this could help scientists more effectively spot promising targets for drug development work.”
The most common Usher 1F mutation is a nonsense mutation.
“According to the team led by French researcher Olivier Goureau from INSERM Paris, tissue-engineered cell sheets may improve the efficacy of cell therapy for tackling retinal degenerative diseases. Based on promising preclinical findings, the researchers are scaling up their protocol with the goal of launching a phase I/IIa clinical trial to prevent vision loss for patients with retinitis pigmentosa – a genetic disorder that leads to progressive deterioration of light-sensing cells in the eye.”
“Ocugen has obtained an exclusive worldwide license to develop and commercialize future ophthalmology products based on groundbreaking technology from the Schepens Eye Research Institute of Massachusetts Eye and Ear. The novel modifier gene therapy platform has the potential to be broadly effective in restoring retinal integrity and function across a range of genetically diverse IRDs and other degenerative retinal diseases, leading to multiple potential product opportunities.”
The FDA has approved Spark Therapeutics’ gene therapy for LCA, a major milestone in the quest for gene therapy for other inherited retinal diseases like Usher 1F.
“Another CDI project aims to restore vision to people with age-related macular degeneration or a disease called retinitis pigmentosa.
“Opsis Therapeutics, a joint venture started last year between CDI and Dr. David Gamm, director of UW-Madison’s McPherson Eye Research Institute, hopes to start a clinical trial within three years.”
“A Spanish research team, based at the Instituto de Investigación Sanitaria La Fe (IIS La Fe), Valencia, have published data showing preliminary proof-of-principle for the use of a new gene editing technology aimed at correcting gene mutations that cause Usher’s syndrome. The technology, known as “CRISPR”, was used to correct mutations in the USH2A gene in cells isolated from patients with the disorder.”
“The idea was a new twist on gene therapy, which typically aims to replace a patient’s own defective version of a gene. Optogenetic gene therapy instead uses a protein from an entirely different species as a workaround. In this case, for people with degenerative diseases such as retinitis pigmentosa, in which the retina’s naturally photosensitive cells die, Pan thought those cells could be bypassed if the retinal ganglion cells that help relay retinal signals to the brain were themselves made light-sensitive.
“In 2006, he and his collaborators published a study showing that the strategy worked in mouse models; the animals ended up with a blue light–sensitive channelrhodopsin in the inner retinal cells, which began transmitting light signals to the visual cortex.”
“These concepts are no longer the stuff of science fiction, but rather real-life science where cells and tissues can be engineered to grow healthy, functional organs to replace diseased ones; where new genes can be introduced into the body to combat disease; and where adult stem cells can generate replacements for cells that are lost to injury or illness,” FDA Commissioner Scott Gottlieb said in a statement. “The promise of this technology is why the FDA is so committed to encouraging and supporting innovation in this field.”
“Awarded a grant of up to $1.6 million from the Small Business Innovation Research program of the National Institutes of Health. The grant provides funding to further develop BioTime’s innovative, next generation vision restoration program for more advanced retinal diseases and injuries, which severely impact the quality of life for millions of people with no treatment option. This initiative aims at improving vision in people affected by blindness, whether caused by retinal injuries, age-related macular degeneration, retinitis pigmentosa or other causes.”
“We are delighted that the Data Safety Monitoring Board has given its approval to progress our ongoing clinical trial in retinitis pigmentosa into its Phase II element,” said chief executive Olav Hellebø.
“Our hRPC cell therapy candidate offers the potential for an entirely new therapeutic option for patients suffering from diseases of the retina such as retinitis pigmentosa and cone-rod dystrophy, and represents a therapeutic platform technology with high commercial potential for ReNeuron.”
More on David Liu’s groundbreaking work on gene editing that he presented at our Usher 1F conference this past May:
“Talk about precision gene editing. Scientists from Harvard University have just unveiled a new gene editor that uses the revolutionary CRISPR-Cas9 technology to target and change a single letter in a string of DNA bases — no cutting necessary.”
“Inherited genetic diseases such as retinitis pigmentosa and nephrogenic diabetes may become treatable if the initial results achieved by a team of researchers led by Prof. Arun Shukla from the Department of Biological Sciences and Bioengineering at the Indian Institute of Technology (IIT), Kanpur, are reproducible in animal models and humans.”
“Previous attempts focused on correcting the genetic mutations which cause blindness by killing off the cells we need to detect light.
“However the new technique provides a single fix, by drafting in completely different cells to do their job. It could be available for patients in five to 10 years.”
“Reactivating lost cone photoreceptor vision might be a breakthrough in addressing retinitis pigmentosa (RP). …The key to the breakthrough was restoration of glucose trapped in the retinal pigment epithelium (RPE) that ultimately reactivated the dormant cones.”
“In vitro factories for producing replacement photoreceptors in eyes with retinal degenerative disorders are becoming an increasingly realistic possibility as stem cell technology continues to advance, according to presentations at the Retina 2016 meeting held in Dublin, Ireland. The potential of the new technologies extends to several aspects of retinal disease. Apart from a cell replacement therapy in the more distant future, in the shorter-term stem cells and stem cell-derived cultures may serve as a means of testing drugs and gene therapy in vitro, said David Gamm MD, PhD, Director of the McPherson Eye Research Institute at the University of Wisconsin, Madison, Wisconsin, USA.”
Guglielmo Lanzani, director of Centre for Nanoscience and Technology at the Italian Institute of Technology, remarked:
“The use of this semiconductor organic material was crucial to address a number of issues. Being organic, this material is soft, light and flexible, provides an excellent biocompatibility also avoiding complications to surrounding tissues, thus ensuring long-term functioning.
“Researchers at the University of Louisville have discovered a way to revitalize cone receptors that have deteriorated as a result of retinitis pigmentosa. Working with animal models, Henry J. Kaplan, M.D., and a group of researchers in the UofL Department of Ophthalmology and Visual Sciences discovered that replenishing glucose under the retina and transplanting healthy rod stem cells into the retina restore function of the cones.”
“MELBOURNE researchers have designed a tiny implantable electrical device to sit unnoticed at the back of the eye and extend the years of useful vision in those most at risk of common causes of blindness.
“Based on a similar concept to the bionic eye but a quarter of the size, the device provides sporadic low-level electrical stimulation to trigger the release of naturally occurring chemicals that prevent retinal cells dying and protect sight.”
“Computer simulations of electrical charges sent to retinal implants based on fractal geometry have researchers moving forward with their eyes focused on biological testing.”
“Powerful new technology may lead to novel therapies to prevent vision loss, blindness in those with diseases of the retina.”
“4D Molecular Therapeutics (4DMT), a leader in adeno-associated virus (AAV) gene therapy vector discovery and product development, and the Foundation Fighting Blindness (FFB), the world’s largest non-governmental source of research funding for inherited retinal degenerations (IRD) and dry age-related macular degeneration (AMD), today announced a partnership to develop intravitreal gene therapeutics for patients with these blinding conditions using 4DMT-proprietary AAV vectors.”
“Our investigational therapy (jCell) uses adult retinal progenitor cells to rescue rods and cones from RP progression and possibly generate new retinal cells. The treatment requires a single intravitreal injection, which can be performed in an ophthalmologist’s office with topical anesthetic. The entire procedure takes less than 30 minutes.
“We have almost completed a phase 1/2a study to determine the therapy’s safety. Early results have been quite promising. So far, the treatment has been well-tolerated and has not generated a detectable immune response, a major concern when transplanting cells.”
“Researchers at Johns Hopkins Medicine report evidence that zebrafishes’ natural ability to regenerate their eyes’ retinal tissue can be accelerated by controlling the fishes’ immune systems. Because evolution likely conserved this mechanism of regenerative potential in other animals, the new findings may one day advance efforts to combat degenerative eye disease damage in humans.”
The National Eye Institute of the US National Institutes of Health (NIH) has launched an ambitious competition for researchers to build a working model of the human retina from stem cells. The initiative, termed the “3-D Retina Organoid Challenge” (see www.nei.nih.gov/3droc) seeks to “clarify the mechanisms of retinal disease, stimulate new technologies and develop more effective therapies.” The project is a component of the NEI’s Audacious Goals Initiative, aimed at restoring vision by “regenerating retinal neurons and their connections to the brain.”
“Peptide bioregulators promote restoration of the physiological activity of the retina in retinitis pigmentosa in older adults and in animal models. The molecular mechanism of the physiological activity of peptides is associated with their ability to epigenetically regulate the synthesis of protein markers of the differentiation of retinal neurons and pigment epithelium.”
“An organic retinal prosthesis has restored light perception in blind rats with retinitis RP, suggesting that restoring sight in humans may soon be possible without the complex hardware required for today’s devices.”
“We found in two separate mouse models of photoreceptor degeneration that tamoxifen, a selective estrogen receptor modulator and a drug previously linked with retinal toxicity, paradoxically provided potent neuroprotective effects. In a light-induced degeneration model, tamoxifen prevented onset of photoreceptor apoptosis and atrophy and maintained near-normal levels of electroretinographic responses.”
“Transplant doctors are stepping gingerly into a new world, one month after a Japanese woman received the first-ever tissue transplant using stem cells that came from her own skin, not an embryo.”
“The University of Pittsburgh is rebuilding its vision programs around a top doctor from France as recent discoveries fuel hopes that new treatments could restore sight to many people who are blind. Sahel aims to treat rare genetic disorders and common causes of blindness.”
“This week we saw encouraging signs that the FDA is serious when it granted Regenerative Medicine Advanced Therapy (RMAT) status to the CIRM-funded jCyte clinical trial for a rare form of blindness. This is a big deal because RMAT seeks to accelerate approval for stem cell therapies that demonstrate they can help patients with unmet medical needs. jCyte’s work is targeting retinitis pigmentosa.”
“Until now, all artificial retinal research has used only rigid, hard materials. The new research, by Vanessa Restrepo-Schild, a 24 year old Dphil student and researcher at the Oxford University, Department of Chemistry, is the first to successfully use biological, synthetic tissues, developed in a laboratory environment. The study could revolutionise the bionic implant industry and the development of new, less invasive technologies that more closely resemble human body tissues, helping to treat degenerative eye conditions such as retinitis pigmentosa.”
“The team, led by Kang Zhang from the University of California, San Diego, used the gene-editing tool, CRISPR, to change the genes that are expressed in rod photoreceptor cells. … There are two types of photoreceptors: rods and cones. Humans have approximately 6 million cones and about 120 million rods. Amazingly, the team observed that turning off these two genes in rods caused the cells to become cone photoreceptors. This “reprogramming” of rods into cones has powerful therapeutic potential, especially for retinitis pigmentosa (RP), which primarily involves the loss of rod photoreceptors.”
“Our approach demonstrates the feasibility of cellular reprogramming in preventing degeneration and preserving tissue and function, and points to a novel approach in treating human diseases in a gene and mutation independent manner,” the authors write.
“The further unraveling of the molecular details of DHA-NPD1-Iduna expression signaling may contribute to possible therapeutic interventions for retinal degenerations and ischemic stroke.” says Bazan.
“It can restore light sensitivity – all without requiring a power supply or any external components. This flexible silk-based iteration gets rid of the glass – and possibly the soft tissue damage and degradation issues of current retinal prosthesis designs.”
“Meanwhile, engineers at the University of California San Diego and the La Jolla-based startup, Nanovision Biosciences Inc. have taken a different approach: optoelectronic silicon nanowires (Figure 2) that can both sense light and stimulate the retina (3). They’re powered by a wireless inductive system that transfers energy with up to 90 percent efficiency,”
MANF has demonstrated positive pre-clinical data in a number of models of retinitis pigmentosa including, a chronic degenerative genetic disorder. The data demonstrates that MANF has the ability to protect rods and cones, as well as improve visual acuity via improvement in cellular electrical signaling.
- S334ter model (University of Miami)
- Rd1 model (Buck Institute on Aging)
- CRX model (Buck Institute on Aging)
- Light-induced damage model (EyeCRO)
“Here we report that BENAQ, an improved photoswitch, is 20-fold more potent than DENAQ and persists in restoring visual responses to the retina for almost 1 month after a single intraocular injection. Studies on mice and rabbits show that BENAQ is non-toxic at concentrations 10-fold higher than required to impart light-sensitivity. These favorable properties make BENAQ a potential drug candidate for vision restoration in patients with degenerative blinding diseases.”
A common pathway involved in photoreceptor death has been identified in retinitis pigmentosa, advanced dry age-related macular degeneration and other retinal diseases, with early evidence of a possible halt to vision loss related to treatment of the pathway.
Bionic Vision Technologies raised AU$23.5 million ($18 million), which will go toward the development and commercialization of its device to restore vision to the blind.
In what’s reported to be a world-first, last Tuesday, a Japanese man received a pioneering retinal cell transplant grown from donor stem cells instead of his own.
“The Foundation Fighting Blindness Clinical Research Institute (FFB-CRI) has announced an investment of up to $7.5 million to advance a promising, emerging drug treatment for retinitis pigmentosa (RP) into and through a Phase II clinical trial. Known as N-acetylcysteine-amide (NACA), the molecule is designed to slow vision loss by protecting retinal cells from oxidative stress. Oxidative stress is a process that accelerates and exacerbates degeneration in many inherited retinal conditions. In several in vitro and in vivo models, including previous FFB-funded lab studies of rodent models at Johns Hopkins University, NACA slowed retinal degeneration.”
A new Wynn Institute for Vision Research study shows that high-resolution 3D-printing can be used to create protective scaffolds that also align patient-specific retinal precursor cells for delivery to the sub-retinal space.
On March 23, 2017, the 2nd Annual Symposium of the CIRM Alpha Stem Cell Clinics Network highlighted the goals of the CIRM ASCC Network, focusing on what has been achieved to date, and discussed pathways toward commercialization and reimbursement of newly developed therapies.
The CIRM Alpha Stem Cell Clinics (ASCC) Network consists of three clinical centers of excellence committed to accelerating the delivery of stem cell therapies. Alpha Clinics are located at City of Hope, UC San Diego, and UCLA in collaboration with UC Irvine.
This study was conducted on a mouse model of Usher 2D.
“Dizziness and hearing loss are among the most common disabilities. Many forms of hereditary balance and hearing disorders are caused by abnormal development of stereocilia, mechanosensory organelles on the apical surface of hair cells in the inner ear. The deaf whirler mouse, a model of human Usher syndrome (manifested by hearing loss, dizziness, and blindness), has a recessive mutation in the whirlin gene, which renders hair cell stereocilia short and dysfunctional. In this study, wild-type whirlin cDNA was delivered to the inner ears of neonatal whirler mice using adeno-associated virus serotype 2/8 (AAV8-whirlin) by injection into the posterior semicircular canal. Unilateral whirlin gene therapy injection was able to restore balance function as well as improve hearing in whirler mice for at least 4 months. Our data indicate that gene therapy is likely to become a treatment option for hereditary disorders of balance and hearing.”
“Silencing a gene called Nrl in mice prevents the loss of cells from degenerative diseases of the retina, according to a new study. The findings could lead to novel therapies for preventing vision loss from human diseases such as retinitis pigmentosa. The study was conducted by researchers at the National Eye Institute (NEI), part of the National Institutes of Health, and was published online today in Nature Communications.”
Usher 1F is caused by a nonsense mutation. This causes the halting of production of proteins necessary for vision. Drugs that cause this stop instruction to be ignored and the proteins necessary for vision to be produced are called translational read-through inducing drugs (TRIDs). Usher 1F Collaborative is currently working with the manufacturer of two TRIDs to begin testing of these drugs on our zebrafish model.
In the new paper they detail their data from the clinical study using sheets of retinal pigmented epithelial cells (RPEs) made from IPS cells in this case derived from the patient herself for autologous use. …you can see the actual transplanted RPE sheet in the eye of the patient. The most encouraging part of this study was that the patient’s vision remained stable (rather than declining as expected) following the treatment. Was that due to the transplant? We can’t be sure.
Also, this is just a beginning as it is just one patient, but it is very exciting and represents a big milestone for the IPS cell and broader stem cell field, providing real hope for patients with vision loss along with parallel ESC-based clinical trial work as well.
“Loss of sight occurs because a gene responsible for maintaining the light sensitive cells at the back of the eye is missing half of its DNA code. But scientists can now replace the code using a groundbreaking technique which reprogrammes the gene in the lab, then delivers the healthy DNA into the eye, via a harmless virus.”
More about the retinal implant that provides better visual acuity than existing implants and doesn’t require an external camera because it’s activated by light.
“Silencing a gene called Nrl in mice prevents the loss of cells from degenerative diseases of the retina, according to a new study. The findings could lead to novel therapies for preventing vision loss from human diseases such as retinitis pigmentosa.”
“With high-resolution retinal prosthesis built from nanowires and wireless electronics, engineers are one step closer to restoring neurons’ ability to respond to light.”
“Medical Marijuana is used widely, and its effects on the visual system and the function of the retina have not been investigated thoroughly. Some evidence suggests that cannabinoids may be beneficial in certain degenerative diseases of the retina.”
“If you were a fish and your retina was damaged, it could repair itself and your vision would be restored in a few weeks.
“Sadly, human eyes don’t have this beneficial ability. However, new research into retinal regeneration in zebrafish has identified a signal that appears to trigger the self-repair process. And, if confirmed by follow-up studies, the discovery raises the possibility that human retinas can also be induced to regenerate, naturally repairing damage caused by degenerative retinal diseases and injury, including age-related macular degeneration and retinitis pigmentosa.”
“The next generation of retinal implants doesn’t require any external hardware. …There have been many ideas on how to use those nerves to restore some level of vision to people with retinal degeneration. These range from biological (using genetic engineering to make other nerve cells in the eye responsive to light) to electronic (using an external camera to send signals to an implant that activates the nerves). This week, researchers from Italy have reported something somewhere between the two: a photovoltaic polymer that acts as a replacement retina, no wires required.”
Researchers at the Inserm-CNRS-UPMC have shown that the ReaChR opsin, a red-sensitive, genetically engineered protein, is a good candidate for restoring vision in patients with Of neurodegenerative diseases of the retina.
“If we get … benefits in humans anywhere near the effects that we’ve seen in our model systems, I think that this will be unprecedented in medicine and in science,” said Kevin Gregory-Evans, a professor in the Department of Ophthalmology and Visual Sciences and the Julia Levy BC Leadership chair in Macular Research.
We hope to soon begin testing of this same drug on our Usher 1F animal model.
The development of a three-dimensional (3-D) transplantable retina may represent the greatest challenge that has ever been addressed in the area of stem cell-based tissue engineering. A team of researchers at AIVITA Biomedical led by Hans S. Keirstead, PhD, has made steady progress along the path and sees the launch of a clinical trial on the horizon.
Scientists present the smallest member of the CRISPR-Cas9 family developed to date and show that it can fit inside adeno-associated viruses and mutate blindness-causing genes… Intraocular injections of AAV-packaged CRISPR-CjCas9 could be beneficial to treat various retinal diseases and systemic diseases. “CjCas9 is highly specific and does not cause off-target mutations in the genome.”
Here, we review the types of stem cells used for treatment of retinal diseases and the findings of some past studies, and we explore the early results and safety concerns related to this technology.
BioTime, Inc. (NYSE MKT:BTX), a clinical-stage biotechnology company developing and commercializing products addressing degenerative diseases, today announced that the company has obtained a world-wide license to intellectual property (IP) assets from University of Pittsburgh. The technology was developed in part in collaboration with BioTime scientists and includes composition and methodologies to develop 3-D retinal tissue constructs from pluripotent stem cells for their implantation in patients with advanced stages of retinal degeneration.
An influential science advisory group formed by the National Academy of Sciences and the National Academy of Medicine on Tuesday lent its support to a once-unthinkable proposition: the modification of human embryos to create genetic traits that can be passed down to future generations….
The advent of a powerful gene-editing tool called Crispr-Cas9 allows researchers to snip, insert and delete genetic material with increasing precision. It has led to plans for experimental treatments of adult patients with cancer, blindness and other conditions as early as this year.
Two startup companies say they plan to start clinical trials to treat blindness by combining an emerging technology called optogenetics with high-tech goggles that can beam light into the eye. Both companies are aiming to help patients with a degenerative eye disease called retinitis pigmentosa, which destroys light-sensing cells in the retina. If the approach works, it could in theory be used to treat any type of retinal disease that involves the loss of these cells, called photoreceptors.
Researchers from Florida Atlantic University are collaborating with scientists from Sancilio and Company, Inc., in Riviera Beach, Fla., to begin a new research project aimed at finding a treatment for patients afflicted by Retinitis Pigmentosa (RP). …Prior preclinical studies performed by scientists at Sancilio and Company, Inc. have demonstrated the potential therapeutic effect of SC412, an investigational drug that the company is currently developing for the treatment of this condition.
While this study was for the deafness of Usher 1C, this virus vector, ANC80, holds great potential for restoring vision as well as hearing in those with all types of Usher Syndrome.
Boston, Mass. — In the summer of 2015, a team at Boston Children’s Hospital and Harvard Medical School reported restoring rudimentary hearing in genetically deaf mice using gene therapy. Now the Boston Children’s research team reports restoring a much higher level of hearing — down to 25 decibels, the equivalent of a whisper — using an improved gene therapy vector developed at Massachusetts Eye and Ear.
“We already know the vector works in the retina,” says Géléoc, “and because deterioration is slower in the retina, there is a longer window for treatment.”
“Progress in gene therapy for blindness is much further along than for hearing, and I believe our studies take an important step toward unlocking a future of hearing gene therapy,” says Vandenberghe, also an assistant professor of ophthalmology at Harvard Medical School. “In the case of Usher syndrome, combining both approaches to ultimately treat both the blinding and hearing aspects of disease is very compelling, and something we hope to work toward.”
START therapy is a bold plan to treat inherited blinding eye disease with an eye drop. Here at the FFB, we are excited about the research that Dr. Cheryl Gregory-Evans and her team are doing to make START therapy a reality.
Dr. Gregory-Evans’ research is focused on a specific kind of mutation called a nonsense mutation. A nonsense mutation is a genetic mutation that functions as a biological stop sign. This stop sign prevents full proteins from being built and instead leads to the production of shorter, unfinished proteins. Usually, these shorter proteins don’t work. START therapy is designed to override the stop sign that is characteristic of nonsense mutations.
Usher 1F is caused by a nonsense mutation.
Researchers have now demonstrated success in grafting healthy eye tissue into previously-blind mice—setting the stage for retinal transplants that could one day restore sight in humans. Mandai and her team hope to start human clinical trials in roughly two years, to find out if grafting retinal tissue from human stem cells can improve sight in people just as well.
Using tadpoles with human RP mutations in their DNA, we found that the drugs had different effects on the tadpole’s photoreceptors depending on their type of mutation: for one type of mutation, the drugs slowed down the retinal degeneration. But, for the three other mutations, the drugs made the condition worse.
Imagine you are trying to put out a fire. You must determine if it’s a wood or a grease fire. Using water to extinguish a campfire works perfectly well, but is highly dangerous to put out a grease fire. The same logic applies to treating RP: in order to stop or slow down the degeneration, it’s important to know the genetic cause.
London: A novel gene-editing method has been found to partially restore sight in rats bred with a hereditary condition called retinitis pigmentosa — a condition that causes blindness in humans.
“The new technology is considerably more efficient than existing methods,” said Pierre Magistretti, Dean of the Biological and Environmental Science and Engineering Division at KAUST.
“The Orphan Drug Designation both in Europe and in the United States, together with the Advanced Therapy Medicinal Product classification in Europe, fully recognize the urgent and unmet medical need for a safe and effective treatment for retinitis pigmentosa patients, and highlight the potential of optogenetics and GS030 to address it,”commented Bernard Gilly, Chief Executive Officer of GenSight Biologics.
GS030 is currently undergoing a Good Laboratory Practices (GLP) regulatory toxicity study, and is expected to enter the clinic with a Phase I/II clinical trial in retinitis pigmentosa patients in Q3 2017, subject to toxicity results and future regulatory review.
Applied Genetic Technologies Corporation, a biotechnology company conducting human clinical trials of adeno-associated virus (AAV)-based gene therapies for the treatment of rare diseases, today announced that it has entered into a strategic research and development collaboration with Bionic Sight, an innovator in the emerging field of optogenetics and retinal coding.
Through the AGTC-Bionic Sight collaboration, the companies seek to develop a new optogenetic therapy that leverages AGTC’s deep experience in gene therapy and ophthalmology and Bionic Sight’s innovative neuro-prosthetic device and algorithm for retinal coding.
Researchers in Japan have demonstrated that photoreceptor cell grafts made from induced pluripotent stem cells (iPSCs) can respond to light and successfully transmit signals to neighboring neurons cells after implantation in the retina in a mouse model of end-stage retinal degeneration.
The study, published Jan. 10 in Stem Cell Reports, represents the first verified instance of cells from a retinal transplant forming functional synapses with the host’s bipolar cells. These intermediary neurons then pass the signal to retinal ganglion cells (RGCs) which in turn, transmit the light information to the brain.
Nearly half of the mice that received iPSC retinal tissue showed some light responsive behavior during tests performed 1.4 to 4 months after implantation, indicating that the grafts not only show potential to restore vision but they may also survive long-term in the host.
This year is off to an exhilarating start with not just one, but two high-profile scientific papers showing that stem cell transplantation can restore vision in blind mice.
The study evaluates performance and safety of IRIS®II in 10 patients suffering from retinitis pigmentosa, Usher Syndrome, Cone-Rod dystrophy, choroideremia will be included and followed for a minimum of 18 months, with additional 18 months follow-up, subject to patient consent.
The IRIS®II clinical trial, initiated in January 2016, is a multi-centric, open label, non-randomized prospective European study to assess effectiveness of the IRIS®II bionic vision system as treatment intended to compensate for blindness, by eventually providing a form of perception for blind persons and enabling them greater autonomy and quality of living. The trial is conducted in prestigious ophthalmology centers in France, the UK, Spain, Austria and Germany.
In the present study, by transplanting mouse iPSC-derived retinal tissue (miPSC retina) in the end-stage retinal-degeneration model (rd1), we visualized the direct contact between host bipolar cell terminals and the presynaptic terminal of graft photoreceptors by gene labeling, showed light-responsive behaviors in transplanted rd1 mice, and recorded responses from the host retina with transplants by ex vivo micro-electroretinography and ganglion cell recordings using a multiple-electrode array system. Our data provides a proof of concept for transplanting ESC/iPSC retinas to restore vision in end-stage retinal degeneration.
Newswise — Rockville, Md. — Vision scientists may have discovered how to reduce pedestrian collisions in crowded and chaotic open space environments like bus terminals, shopping malls and city plazas involving individuals with partial blindness. Researchers have determined from which direction collisions with partially blind pedestrians are most likely to originate. This understanding will guide the development of new glasses that expand the sight of a person with limited peripheral vision.
“Rosie had what are called retinal progenitor cells injected into her eye, part of a treatment developed by Dr. Henry Klassen at the University of California, Irvine. The hope was that those cells would help repair and perhaps even replace the light-sensing cells damaged by the disease.
“Following the stem cell treatment, gradually Rosie noticed a difference. It was small things at first, like being able to make out the colors of cups in her kitchen cupboard, or how many trash cans were outside their house.”
“The quantity of information transferable to the retina using existing implant technologies is limited, far below receptor cells’ capabilities. Many agree that increasing the information density deliverable by a retinal prosthesis requires devices with stimulation electrodes that are both dense and numerous. This work describes a new generation of retinal prostheses capable of upscaling the information density conveyable to the retina.”
“The objective of this review is to summarise the scientific evidence on the effectiveness and safety of nutritional supplements for the treatment of HRDs.”
“Safety and tolerability data from the Phase I part of the study in the first nine patients are expected in the first half of 2017, with longer term safety data as well as efficacy read-outs from the Phase II part of the study in a further six patients expected in the second half of 2017.”
“Researchers have discovered a holy grail of gene editing — the ability to, for the first time, insert DNA at a target location into the non-dividing cells that make up the majority of adult organs and tissues.”
“A Chinese group has become the first to inject a person with cells that contain genes edited using the revolutionary CRISPR–Cas9 technique.”
“Columbia University Medical Center (CUMC) researchers have demonstrated that vision loss associated with a form of retinitis pigmentosa (RP) can be slowed dramatically by reprogramming the metabolism of photoreceptors, or light sensors, in the retina. The study, conducted in mice, represents a novel approach to the treatment of RP, in which the therapy aims to correct downstream metabolic aberrations of the disease rather than the underlying genetic defect.”
“Recent advances in molecular genetics and cell biology are elucidating the pathophysiological mechanisms underlying these disorders and are helping to identify new therapeutic approaches, such as gene therapy, stem cell therapy, and optogenetics. Several of these approaches have entered the clinical phase of development.”
“The holy grail of bionic eyes, which would allow people with the most incurable causes of blindness to read large print, is about to begin preclinical testing in Melbourne.”
“The Cell and Gene Therapy Catapult, set up by the UK government to promote the technology, says ophthalmology is the most popular field for pre-clinical cell and gene therapy research, accounting for 14 out of 60 UK studies in all areas. These experimental therapies are judged to be three years or less from starting clinical trials in patients.”