Cell-based therapies and gene-independent approaches have the potential to benefit anyone with Usher syndrome, regardless of their subtype. Examples include stem cells, retinal progenitor cells, neuroprotection, optogenetics, nutritional approaches, etc. Here, we outline the various approaches that have the potential to help anyone living with Usher syndrome.
Each research project listed below will include a graphic of the research continuum. The gold box indicates where this project falls on the continuum, illustrating its progress towards reaching people living with Usher syndrome, from "Bench to Bedside."
Click here to learn more about the different stages in the research continuum.
Safety and Efficacy of NPI-001 Tablets for RP Associated With Usher Syndrome (SLO RP)
Dr. Lee Anderson with sponsors and collaborators from Nacuity Pharmaceuticals Inc. and Foundation Fighting Blindness in Australia are looking at NPI-001 Tablets, an antioxidant drug. Their study will examine the safety and efficacy of these oral NPI-001 Tablets compared to placebo tablets for participants who have vision loss due to retinitis pigmentosa (RP) with Usher syndrome. The study takes place over the course of 24 months. This study is expected to be completed in September 2023.
Nacuity Pharmaceuticals Info Page
Link to study details on ClinicalTrials.gov
Stem Cell Therapy for USH
Edwin Stone, M.D., Ph.D.:
University of Iowa
Stone and his team at the University of Iowa are working to develop a cure for Usher syndrome along with other types of retinitis pigmentosa. They are working to halt further retinal degeneration from USH1F through gene replacement and to repair damaged retinal photoreceptor cells with new cells made from the patient's own skin cells with the goal of a clinical trial once safety and efficacy are determined.
The University of Iowa Institute for Vision Research
Clinical Trial for Safety and Tolerability of hRPC in Retinitis Pigmentosa (hRPCRP)
ReNeuron, a UK-based stem cell research company, that focuses on developing stem-cell therapies that target areas of "significant unmet or poorly met medical need." They have used their stem cell technologies to develop cell-based therapies for significant diseases where cells can be readily administered to any eligible patient without the need for additional drug treatment. Currently, they are developing the human retinal progenitor cell line (hRPC) for the treatment of retinal diseases such as retinitis pigmentosa (RP).
- Positive Preliminary Data: Significant improvement in vision in first cohort of Phase II subjects in US trial of hRPC cell therapy in retinitis pigmentosa (February 20, 2019)
- ReNeuron Website
- Additional Information on hRPCs for Retinal Diseases
- Clinical Trial for the Safety and Tolerability of hRPC in Retinitis Pigmentosa (hRPCRP)
Clinical Trial for Safety and Efficacy of Intravitreal Injection of Human Retinal Progenitor Cells in Adults With Retinitis Pigmentosa
jCyte was founded in 2012 by Drs. Henry Klassen and Jing Yang, who have spent decades investigating the mechanisms that drive retinitis pigmentosa (RP) and other retinal diseases. Their work led to the creation of retinal progenitor cells (RPCs), a type of stem cell that can only become retinal cells. Clinical studies have shown that these cells could rescue and even replace diseased retinal cells. Early results from a phase 1/2a study have shown the treatment is safe and does not trigger an immune response. They have completed the enrollment and recruitment for their current phase 2b trial.
- jCyte Website
- Additional Information on jCells
- ClinicalTrials.gov listing for Phase 1/2a Study
- ClinicalTrials.gov listing for Phase 2b Study
Cedars-Sinai, a non-profit healthcare organization based in Los Angeles, has received authorizations from the FDA to launch a 16-person, Phase 1/2a clinical trial of human neural progenitor cells--stem cells that have almost developed into neural cells--for patients with RP. The trial is being funded by a $10.5 million grant from the California Institute for Regenerative Medicine. The study's principal investigator is Clive Svendsen, PhD, professor of Biomedical Sciences and Medicine and director of the Cedars-Sinai Board of Governors Regenerative Medicine Institute.
Gene-Independent Approaches: Related Science News
In the summer of 2022, Endogena launched its first dosing of its phase 1/2a study of EA-2353 in retinitis pigmentosa (RP).
In a guest column at clinicalleader.com, the authors discuss the past and exciting future prospects of optogenetic therapies.
Researchers at the University of Wisconsin School of Medicine and Public Health were able to create retinal cells from human stem cells that can detect light and change it to electrical waves.
Researchers in China successfully created an induced-pluripotent stem (iPS) cell line using immune cells from the blood of a patient with Usher syndrome type 2A.
Researchers at Newcastle University are looking into creating treatments for common inherited eye conditions.
A recent biotechnology breakthrough is the organ-on-chip (OOC) technology.
AIVITA Biomedical Inc., a biotech company that specializes in new ways of using stem cells, recently conducted a preclinical study. Using human stem cells that they created, researchers created and tested a “total retina patch” for vision loss.
GenSight Biologics is a biopharmaceutical company that focuses on creating gene therapies for retinal neurodegenerative and central nervous system disorders. They have announced that the FDA has awarded Fast Track Designation of GS030, which uses AAV2 gene therapy combined with optogenetics to treat retinitis pigmentosa.
Researchers have been exploring stem cell therapies to treat vision loss, including vision loss caused by retinitis pigmentosa. Preclinical and clinical studies are showing that stem cell therapies could be new options.
A Phase 2 clinical trial was used to see if injecting human retinal progenitor cells (derived from stem cells) can improve vision and visual fields in people with retinitis pigmentosa (RP).
Nanoscope Therapeutics Inc., a clinical-stage biotechnology company, has recently announced that one of its drugs is approved for Phase 2b clinical trial.
Retinitis pigmentosa (RP) is a rare genetic disease that causes loss of photoreceptors, which are the light sensitive cells in the retina. This disease can lead to blindness and affects more than 2 million people worldwide. In a groundbreaking clinical trial led by Paris-based GenSight Biologics, a man who was blind for 40 years successfully regained some visual function with a technique called optogenetics. Optogenetics uses light to control neuron activity. In this study, a light-sensing protein called ChrimsonR was injected into the eye and delivered to the patient’s retinal cells. After a four-month period to allow his body to make ChrimsonR protein, the patient was fitted with special goggles that detect and shift incoming light into a specific color range. The patient was able to see high-contrast images and objects, and his brain activity was the same as someone with normal sight.
What this means for Usher syndrome:
More patients will need to be enrolled and evaluated, but if this study proves to be successful, RP patients who are blind may be able to regain some sight, increasing their quality of life. Because vision loss in Usher syndrome is a type of RP, this therapy may also be beneficial for Usher syndrome patients.
Individuals that have permanent damage to their photoreceptors are unable to repair or regenerate new photoreceptors. Researchers and engineers may have a possible solution for these individuals living with vision loss. They have worked to make new photoreceptors and a micro-molded scaffolding photoreceptor “patch.”
Magdalene Seiler, Ph.D., UCI associate professor has been awarded a five-year grant of $3,823,950 from the National Institutes of Health to do a preclinical study using rodent models. This study looks at an innovative co-graft method to permanently repair damaged retinas.
Photoreceptor precursor cells that were generated from stem cells were able to be successfully transplanted into the retina and demonstrate basic visual function.
In a recent study, retinal cells coming from adult human eye stem cells were successfully put into the eyes of monkeys.
An interdisciplinary team of scientists funded by University of Toronto’s Medicine by Design initiative believes they can improve the outcomes of conditions like age-related macular degeneration and retinitis pigmentosa.
Journalists at Fierce Biotech summarized exciting research from the Centre for Genomic Regulation in Barcelona. They are studying how stem cell biotechnology can be improved in retina disease treatment models.
Lentivirally modified mesenchymal stem cells from bone marrow shows promise in preserving retinal function and preventing further retinal degradation.
Vedere Bio, Inc., a company focused on photoreceptor-protein-based optogenetic therapies (use of light to modulate neurons that have been genetically modified) to restore vision has been acquired by Novartis.
Intravitreal injection of human retinal progenitor cells (hRPCs;jCells) is a novel stem cell treatment currently in development for retinitis pigmentosa (RP. In a recently completed phase 2b study, this treatment was injected into the jelly-like center or vitreous of the eye and has demonstrated promising biologic activity and an excellent safety profile. In this study, 84 patients diagnosed with RP and with best-corrected visual acuity (BCVA) between 20/80 to 20/800 were randomly assigned to 2 different doses (low or high) of jCells or a placebo. The primary end point (or target outcome) was the mean change in the BCVA at 12 months; the secondary end points were identification of the lowest light level at which patients could navigate through a structured mobility maze, along with the mapping of each patient’s kinetic visual field, the evaluation of their performance on contrast sensitivity testing, and completion of a low vision–specific quality-of-life questionnaire. In a post hoc analysis of this target population, an early and significant improvement in vision was seen in the higher-dose group, with average gain of 16 letters at month 12 compared with 2 letters in the control group. Improvement in the higher-dose group compared to the control group was also true for the secondary outcomes. While there were some mild cases of eye inflammation and one severe case of hypertension associated with treatment, these adverse effects were addressed. These study results showed that intravitreal injection of allogeneic jCells that were not derived directly from the patient shows promising results. The study is expected to continue with expected redosing of patients and further monitoring as this treatment is not expected to be permanent.
What this means for Usher syndrome: These results from a Phase 2b study demonstrate that intravitreal injection of retinal progenitor stem cells shows measurable improvement in vision and may be a viable treatment option in the future for both Usher and RP patients.
Researchers have discovered a technique for directly reprogramming skin cells into light-sensing rod photoreceptors used for vision. The laboratory-made rods enabled blind mice to detect light after the cells were transplanted into the animals’ eyes. According to Anand Swaroop Ph.D., senior investigator, “This is the first study to show that direct, chemical reprogramming can produce retinal-like cells, which gives us a new and faster strategy for developing therapies for age-related macular degeneration and other retinal disorders caused by the loss of photoreceptors.” The immediate benefit of this technique will be the ability to develop models to allow us to study the mechanisms of the disease and design better cell replacement approaches. Induced pluripotent stem (IPS) cells take about six months to create, however direct reprogramming takes only about ten days to convert skin cells into functional photoreceptors. A clinical trial to test the therapy in humans for degenerative rental diseases such as retinitis pigmentosa is in the works.
What this means for Usher syndrome: This new technique holds promise for treatment of many retinal degenerative diseases, including Usher syndrome.
Stem cell technology has enabled new possibilities for understanding and treating rare diseases such as Usher syndrome. The technology for stem cell treatment is still relatively new and complex. Unfortunately, several private clinics are attempting to financially capitalize on patients’ desperation and confusion for a cure. David Gamm, MD, PhD, a researcher at the University of Wisconsin-Madison, wrote an article for Foundation Fighting Blindness explaining the ten things we should know before falling victim to a retinal stem cell scam. Even if the treatment does not cause physical harm, it can result in significant financial damage; therefore, it is important to be aware of these scams.
The ReNeuron Group has announced positive long-term data from its ongoing phase 1/2a clinical trial of its hRPC (human retinal progenitor cells) stem cell therapy candidate in Retinitis Pigmentosa. In October 2019 at the American Academy of Ophthalmology Meeting in San Francisco, data presented by Pravin Dugel, MD showed “a group of subjects who had a successful surgical procedure with sustained clinically relevant improvements in visual acuity compared with baseline, as measured by the number of letters read on the ETDRS chart.” The company has submitted a protocol amendment to the FDA to expand their 1/2a study to treat up to a further nine patients in the phase 2a segment of the study with a dose of two million hRPC cells compared to the dose of one million cells used so far. The amended trial protocol allows for a greater range of pre-treatment baseline visual acuity in patients and includes changes that enhance the ability to use microperimetry testing to measure and detect changes in retinal sensitivity in patients treated. If the amendment is approved the company expects to have sufficient data to commence a pivotal clinical study with its hRPC cell therapy candidate in RP by 2021. Furthermore, this clinical program has been granted Orphan Drug Designation in Europe and the US, as well as Fast Track designation from the FDA.
What this means for Usher syndrome:That Usher patients may benefit from this stem cell therapy in the near future if the amendment is approved and the company obtain sufficient data for the initiation of the pivotal clinical trial .
The aim of this study is to determine if umbilical cord Wharton’s jelly derived mesenchymal stem cells implanted in sub-tenon space have beneficial effects on visual functions in RP patients by reactivating the degenerated photoreceptors in dormant phase. 32 RP patients participated in the study and were followed for 6 months after the Wharton’s jelly derived mesenchymal stem cell administration. Regardless of the type of genetic mutation, sub-tenon Wharton's jelly derived mesenchymal stem cell administration appears to be an effective and safe option. There are no serious adverse events or ophthalmic / systemic side effects for 6 months follow-up. Although the long-term adverse effects are still unknown, as an extraocular approach, subtenon implantation of the stem cells seems to be a reasonable way to avoid the devastating side effects of intravitreal/submacular injection.
What this means for Usher syndrome: If successful, this stem cell therapy will help Usher patients to recover their vision while minimizing the invasive adverse effects of the treatment.