Usher Syndrome Blog and News
The latest USH blog posts and various news items impacting the Usher syndrome community. Join our mailing list.
Lane, a mother of two children with Usher Syndrome, writes about her experience at the Usher syndrome Coalition Annual Conference. She explains how these conferences have positively affected not just herself but her whole family.
This study discovered that a classic anti-malarial drug can help sensory cells of the inner ear recognize and transport the Clarin-1 protein to its normal location in the cell. Usher syndrome 3A is due to mutations in Clarin-1. The researchers found that the mutant Clarin-1 protein is not transported properly and then tested drugs that target the transport system. They found that the drug, artemisinin, restores inner ear sensory cell function, and thus hearing and balance, in zebrafish genetically engineered to have mutant human versions of the Clarin-1 protein.
What this means for Usher syndrome: This study identifies a drug that might be useful for treating hearing loss in Usher syndrome 3A patients.
This study aims to analyze the effect of nutraceutical molecules with antioxidant properties, on progression of the disease in an established animal model with retinitis pigmentosa (RP). We saw that long-term treatment with a flavanone (naringenin) or flavanol (quercetin) present in citrus fruits, grapes, and apples, preserves retinal functionality. These two molecules possess antioxidant properties, limiting neurodegeneration, and thus preventing cone damage.
What this means for Usher syndrome: If this treatment preserves cone functionality, it could slow vision loss in Usher syndrome patients.
OliX Pharmaceuticals Inc., a leading developer of RNAi therapeutics announced today an expansion of its ocular disease pipeline. OLX304A has been developed as an RNAi therapeutic with an undisclosed target for the treatment of Retinitis Pigmentosa. OLX304A is a program to develop a treatment that targets a single gene for patients with Retinitis Pigmentosa regardless of their disease-causing mutation. This treatment is different from conventional strategies that focus on targeting individual disease-causing genes.
What this means for Usher syndrome: This strategy could result in a single type of treatment that could help all Usher syndrome patients.
Eloxx Pharmaceuticals is developing small molecules that permit read-through of point mutations that cause Usher syndrome 1F and 2A. Eloxx has entered into a partnership with the Foundation Fighting Blindness and is developing molecules that “read through” nonsense mutations. Scientists believe that approximately 10% of all the gene mutations across all known inherited retinal diseases are nonsense. Therefore, the “read through” molecules have the potential to help many people.
What this means for Usher syndrome: A subset of Usher syndrome patients, those with nonsense mutations, might be helped by this therapy.
ReNeuron Group plc has announced the latest updated positive preliminary results in the company’s ongoing phase 1 and 2a clinical trial of its human retinal progenitor cell (hRPC) therapy candidate in retinitis pigmentosa. All three subjects in the first group of phase 2a have demonstrated a sustained and further improvement in vision compared to their pre-treatment baseline.
What this means for Usher syndrome: This potential therapy could provide a means to restore lost vision in Usher syndrome patients.
2Ctech Inc, a privately-held development stage company focused on the application of nanoparticle technologies for the treatment of retinal diseases, announced its first-known clinical program to demonstrate the effectiveness and safety of Quantum Dots (QDs) to achieve photovoltaic stimulation of the neural retina for preservation or enhancement of vision in patients with retinal degenerative diseases. QDs are semiconductor crystalline structures that absorb light and generate a dipole electrical field; thus, stimulating the neuronal retina cells. These particles are similar to solar cells, which produce energy in response to light. In the layers of the retina, the particle emissions are intended to result in direct stimulation of the neural retina, “creating action potentials that trigger the normal neural pathways to the brain.
What this means for Usher syndrome: This new technology holds promise to provide a means to restore lost vision in Usher syndrome patients.
Karen Andersen, Samira Kiani and their colleagues at Arizona State University described a method of rendering the CRISPR-Case9 gene-editing tool “immunosilent,” potentially allowing the editing and repair of genes to be accomplished reliably and without activating an immune response. Their study is the first to predict accurately the dominant binding sites or epitopes responsible for immune recognition of the Cas9 protein and experimentally target them for modification. These findings bring CRISPR a step closer to a safer clinical application.
What this means for Usher syndrome: This discovery could help pave the way toward FDA approval of CRISPR/Cas9 gene editing therapies to treat Usher syndrome.
Ophthotech has licensed exclusive rights to develop novel adeno-associated virus (AAV) gene therapy candidates for Best disease and other bestrophinopathies from University of Pennsylvania (Penn) and the University of Florida Research Foundation (UFRF). The agreement allowed Ophthotech to enter talks with Penn and UFRF to acquire a license for novel AAV serotype 2 based gene therapy product candidates for Best disease, an orphan inherited degenerative retinal disease caused by mutations in the BESTI gene. Additionally, Ophthotech says it expects to initiate a Phase I/II clinical trial for the Best disease candidate in the first half of 2021.
What this means for Usher syndrome: If the first clinical trials for Best disease using this novel AVV gene therapy are successful, this means Ophthotech will probably look for other eye-related diseases like Usher syndrome.
RNA, the short-lived cousin to its better-known partner, DNA, is the blueprint for protein production in cells. Joshua Rosenthal told researchers about how the squid and octopuses make prolific use of an enzyme called ADAR to catalyze thousands of single-letter changes to the RNA code. These minor edits alter the structure and activity of proteins that control electrical impulses in the animals’ nerves. Rosenthal’s studies on squids inspired him to hijack ADAR and program it for making precise edits to the human RNA. Additionally, the editing of RNA is reversible, since cells are constantly churning out new copies of RNA. If Rosenthal’s RNA editors work in humans, they could be used repeatedly to treat genetic diseases without confronting the unknown, long-term risks of permanent DNA editing with CRISPR.
What this means for Usher syndrome: Although too early to say, RNA-reversibly editing can develop in an alternative strategy for the repair of point mutations in Usher genes.
Adeno-associated viruses (AAV) engineered to target specific cells into the retina can be injected directly into the vitreous of the eye to deliver genes more precisely than with wild type AAVs, which must be injected directly under the retina. Researchers at the University of California, Berkeley inserted a gene for a green-light receptor into the eyes of blind mice, and a month later the mice could maneuver obstacles as easily as mice without visual impairments. The mice could use motion, brightness changes over time, and fine detail on an iPad.
What this means for Usher syndrome: Retinal delivery of AAV can always have the adverse effects of tissue inflammation and/or retinal detachment. This new strategy, delivering the modified virus into the vitreous, will prevent those side effects. For Usher patients, this means that, if successful, this therapy will increase the probability of success in restoring vision.
Stem cells are cells that have the capability of becoming any type of cells in an organism and in the right environment. Researchers are trying to use stem cell therapy to replace lost photoreceptors and preserve residual photoreceptors during retinal degeneration. One of the problems is that the degenerative microenvironment that already exists in the diseased retina compromises the fate of grafted cells. The desired donor cells will need to have both proper regenerative capability and the ability to improve their own microenvironment. For this purpose, the authors of the present work used specific cell surface molecules that help to kill tumorigenic embryonic cells and at the same time enrich retinal progenitor cells. The retinal progenitors were obtained from embryonic stem cells derived from retinal organoids (three dimensional structures derived from pluripotent cells) that were grafted into retinal degeneration rat and mouse models. After three months post-treatment, those animals showed a 40% increase in healthy photoreceptor cells and a decrease in inflammatory molecules, demonstrating the importance of a healthier environment for the grafted cells.
What this means for Usher syndrome: These two features of the organoid systems, regenerative capability and generation of a healthier microenvironment, will, very likely, benefit Usher patients as an additional therapy to delay or prevent photoreceptor loss.
Ganglion cells in the eye generate noise as the light-sensitive photoreceptors die in diseases such as retinitis pigmentosa (RP). Now, neurobiologists have found a drug and gene therapy that can tamp down the noise, improving sight in mice with RP. These therapies could potentially extend the period of useful vision in those with degenerative eye diseases, including, perhaps, age-related macular degeneration.
What this means for Usher syndrome: This type of therapy may also extend the period of useful vision in Usher syndrome.
ProQR Therapeutics N.V., a company dedicated to changing lives through the creation of transformative RNA medicines for the treatment of severe genetic rare diseases, today announced the first patient treated in the Phase 1/2 STELLAR clinical trial for QR-421a in patients with Usher syndrome type 2 or non-syndromic retinitis pigmentosa (RP). Interim data from the trial are expected to be announced by mid-2019. According to David G. Birch, Ph.D., Principal Investigator of STELLAR and Scientific Director of the Retina Foundation of the Southwest in Dallas, Texas, “The STELLAR study is one of the first studies of its kind exploring the impact of ProQR’s RNA therapies on patients with Usher syndrome type 2 due to an Exon 13 mutation. The STELLAR trial will explore whether QR-421a (ProQR’s RNA therapy) can slow disease progression or even reverse it.”
What this means for Usher syndrome: There may be a potential drug available to reverse blindness caused by Usher syndrome.
Researchers at the University of Science and Technology of China injected tiny nanoparticles into mouse eyes that bind the retina into the eyeballs, hence giving them what the team calls ‘super vision.’ The injected nanoparticles bind to photoreceptors and shift the wavelength of light. After the injection, the mice could see normally invisible near-infrared light effectively extending ‘mammalian vision’. Scientists predict that these kinds of nanoparticles could help repair vision in humans who experience loss of retinal function or red color blindness. Additionally, this method is less invasive than other conventional vision repair methods.
What this means for Usher syndrome: This method might be used to increase light sensitivity as vision is lost.
The USH2019 Early Bird Rate has been extended to March 15th and there are new opportunities to connect at this annual Usher syndrome event!
ReNeuron Group, a UK-based global leader in the development of cell-based therapeutics, announced positive preliminary results in the company’s ongoing Phase 1/2 clinical trial of its human retinal progenitor cells candidate therapy for the blindness-causing disease, retinitis pigmentosa (RP). All three subjects in the first group of the Phase 2 part of the trial demonstrated a significant improvement in vision at the follow-up compared to their pre-treatment baseline and compared with their untreated control eye.
What this means for Usher syndrome: A similar cell-based therapy tailored to Usher syndrome may help restore vision.
The Sanford Health Lorraine Cross Award worth $1 million was established to award game-changers in medicine. The award is not to have people to live forever, but to “live life without suffering.” The winners of the award are Dr. Jean Bennett and Dr. Katherine High of the University of Pennsylvania, pioneers of gene therapy research. The award is in recognition of the improvements in gene therapy that led to an FDA-approved treatment for Leber’s congenital amaurosis.
What this means for Usher syndrome: This award not only reflects the importance of gene therapy for the treatment of genetic disorders but could accelerate research in Usher syndrome through gene therapy.
A team of scientists from Sechenov First Moscow State Medical University (MSMU), together with colleagues from leading scientific centers in India and Moscow, described several genetic mutations causing Usher syndrome.
What this means for Usher syndrome: These previously unstudied genetic mutations will allow us to identify new targets for specific therapies.
The United States Patent & Trademark Office (USPTO) has approved the usage of mesencephalic-astrocyte-derived neurotrophic factor (MANF) or cerebral dopamine neurotropic factor (CDNF) as a treatment for various retinal disorders including retinitis pigmentosa, macular degeneration, or glaucoma. Both factors can be administered as an eye drop or by intravitreal injection. MANF is believed to have potential because it is a naturally-occurring protein produced by the body to reduce or prevent cell death in response to injury or disease through unfolded protein response.
What this means for Usher syndrome: Since MANF reduces or prevents cell death, in the case of Usher syndrome, it could prevent photoreceptor cells from dying, and thus preserve vision.
Join us for our 11th annual USH Connections Conference in Philadelphia, Pennsylvania on July 13, 2019. Attendees describe this conference as "life-changing," an event with a positive atmosphere and a genuine sense of community. At the USH Connections Conference, you will connect face-to-face with hundreds of people who "get it", meet and network with others facing the same challenges, and learn the latest on developing treatments from leading USH researchers.
A new purple protein, bacteriorhodopsin, has made its way from a tiny laboratory in Farmington, Connecticut, all the way up to the International Space Station. Since bacteriorhodopsin is light-sensitive, researchers hope to implant it into human eyes. The thought is that the protein could be used to replace cells that die due to diseases like retinitis pigmentosa and age-related macular degeneration. To simulate the cells, the laboratory in Farmington needs to build what it is called “organic implants” by layering the bacteriorhodopsin onto a film and dipping it over and over into a series of solutions. These solutions need to have a uniform distribution that can be adversely affected by gravity. To test this, LambdaVision has secured a spot for their experiment aboard the International Space Station, using funding from the ISS National Lab and Boeing.
What this means for Usher syndrome: These “organic implants”, composed of bacteriorhodopsin, could be capable of replacing dying photoreceptors in the retina.
Researchers revealed that culturing human induced pluripotent stem cells with different isoforms of the extracellular component laminin led to the creation of cells specific to different parts of the eye, including retinal, corneal, and neural crest cells. They showed that the different laminin variants affected the cells' motility, density, and interactions, resulting in their differentiation into specific ocular cell lineages. Cells cultured in this way could be used to treat various ocular diseases.
What this means for Usher syndrome: There is the possibility of replacing the photoreceptor cells that are dying in the retina with pluripotent cells that have been grown and induced into healthy photoreceptor cells.
Scientists at the Francis Crick Institute have discovered a set of simple rules that can determine the precision of CRISPR/Cas9 genome editing in human cells. These rules could help to improve the efficiency and safety of genome editing in both the lab and the clinic. By examining the effect of CRISPR genome editing at 1491 target sites across 450 genes in human cells, the team have discovered that the outcomes can be predicted based on simple rules. In this study, researchers have found that the outcome of a particular gene edit depends on the fourth letter from the end of the RNA guide, synthetic molecules made up of about 20 genetic letters (A, T, C, G). “The team discovered that if this letter is an A or a T, there will be a very precise genetic insertion; a C will lead to a relatively precise deletion and a G will lead to many imprecise deletions. Thus, simply avoiding sites containing a G makes genome editing much more predictable.”
What this means for Usher syndrome: Scientists will theoretically be able to repair the mutation present in an Usher gene by selecting the correct genetic letter from the end of the RNA guide.
ProQR Therapeutics announced that the FDA has cleared the Investigational New Drug (IND) application for QR-421a. QR-421a is a first-in-class investigational RNA-based oligonucleotide designed to address the underlying cause of the vision loss associated with Usher syndrome type 2 and non-syndromic retinitis pigmentosa due to mutations in exon 13 of the USH2A gene. ProQR plans to start enrolling patients in a Phase 1/2 trial named STELLAR in the coming months with preliminary data expected in mid-2019.