Dallas-based Nacuity has launched a Phase ½ clinical trial in Australia for its oral antioxidant therapy. The trial is for people with Usher syndrome. The Foundation Fighting Blindness is investing up to $7.5 million to advance the promising, emerging drug for retinitis pigmentosa, Usher syndrome, and related conditions. Known as N-acetylcysteine-amide (NACA), the molecule is designed to slow vision loss by protecting retinal cells from oxidative stress. In previous Foundation-funded lab studies at Johns Hopkins University, NACA slowed retinal degeneration in rodent models of RP.
FOUNDATION FIGHTING BLINDNESS CONDUCTING RUSH2A NATURAL STUDY FOR PEOPLE WITH USH2A MUTATIONS
The Foundation Fighting Blindness has launched a natural history study for people with mutations in the USH2A gene, which are leading causes of Usher syndrome and retinitis pigmentosa. A major goal of the study, known as RUSH2A, is to better understand the course of vision loss in people with USH2A mutations, so that researchers can design successful clinical trials for potential therapies and identify patients for the treatment studies. More than 100 patients are enrolled at approximately 20 sites in the US, Canada, and Europe.
FOUNDATION LAUNCHES USH1F NATURAL HISTORY STUDY
The Foundation is partnering with the Usher 1F Collaborative, a family-founded nonprofit driving research for Usher syndrome type 1F (USH1F), to launch a natural history study, the Rate of Progression in PCDH15-Related Retinal Degeneration in Usher Syndrome 1F (RUSH1F). Additional funding for the project will be provided by the Marjorie C. Adams Trust. USH1F is a subtype of Usher syndrome caused by mutations in the gene PCDH15.
ATSENA THERAPEUTICS DEVELOPING USH1B GENE THERAPY
Atsena Therapeutics is developing a dual vector AAV gene therapy for people with mutations in MYO7A, the gene, when mutated, causes Usher syndrome 1B. The Foundation is funding Atsena through its RD Fund, a venture philanthropy fund for emerging therapies in, or moving toward, clinical trials.
SMALL MOLECULE FOR USH3A MOVING TOWARD CLINICAL TRIAL
Dr. Farhan is completing pre-IND toxicity studies to advance a novel small-molecule therapy for USH3A into a Phase 1 clinical trial. The emerging drug works by stabilizing the misfolded USH3A protein (clarin-1) and enabling it to better move to its target location in retinal cells, thereby striving to preserve structure and function.
THÉA ACQUIRES PROQR’S EMERGING RNA THERAPY FOR USH2A EXON 13 MUTATIONS
Théa has acquired ProQR’s RNA therapy for people with Usher syndrome 2A or non-syndromic retinitis pigmentosa caused by mutations in exon 13 of the gene USH2A. Previously, ProQR reported that some patients in its Phase ½ clinical trial for the emerging treatment showed vision improvements. Théa plans further clinical development of the USH2A RNA therapy.
JANUARY 2024
]]>Laboratoires Théa, the leading European developer of eye care products, has acquired two emerging antisense oligonucleotide (AON) treatments for inherited retinal diseases from ProQR Therapeutics. Both AON therapies — sepofarsen (LCA10) and ultevursen (USH2A) — previously demonstrated vision improvements in ProQR’s clinical trials.
In October 2023, Théa had announced termination of its agreement to acquire ProQR’s LCA10 and USH2A assets, but the companies have since moved forward to ultimately complete the acquisition.
Under the terms of the agreement, ProQR has received an initial payment of €8M and may be eligible for up to €165M in further development, regulatory, and commercial earn-out payments upon related achieved milestones, as well as double-digit royalties based on commercial sales in the US and EU.
The RD Fund, the venture philanthropy arm of the Foundation Fighting Blindness, invested in the development of ultevursen and supported ProQR’s effort to find a buyer for both of its ophthalmic assets.
“We are delighted that Théa’s acquisition of sepofarsen and ultevursen has been completed and to see these promising treatments move forward in clinical development,” says Jason Menzo, chief executive officer, Foundation Fighting Blindness. “Both emerging therapies have demonstrated encouraging results in human studies and provide hope for preserving and restoring vision for patients.”
Sepofarsen was developed for people with Leber congenital amaurosis 10 (LCA10) caused by the IVS26 mutation in the gene CEP290. Some patients in ProQR’s Phase 2/3 Illuminate clinical trial for sepofarsen had meaningful vision improvements. However, the treatment did not meet its primary trial endpoint, best-corrected visual acuity (BCVA), nor did it meet its secondary endpoint, navigation of a mobility course.
Ultevursen was developed for people with mutations in exon 13 of the USH2A gene which leads to Usher syndrome 2A or non-syndromic retinitis pigmentosa. In ProQR’s Phase 1/2 Stellar clinical trial, ultevursen demonstrated benefits in BCVA, static perimetry (retinal sensitivity), and retinal structure as measured by optical coherence tomography (OCT).
Both sepofarsen and ultevursen are comprised of tiny pieces of genetic material that are injected into the vitreous, the soft gel in the middle of the eye. The genetic material masks the disease mutation in RNA, the genetic messages that cells read to make proteins which are critical for the cells’ health and function. Masking the mutation enables cells to make the correct protein.
AONs can be advantageous when large retinal disease genes — such as CEP290 and USH2A — exceed the capacity of viral gene replacement delivery systems thereby making gene therapy development for these genes more challenging.
]]>Previously, ProQR reported that sepofarsen did not meet its endpoints for efficacy in a Phase 2/3 clinical trial. The European Medicines Agency subsequently recommended that ProQR conduct another clinical trial for sepofarsen before seeking marketing approval in Europe.
ProQR has not yet reported any results for its Phase 2/3 clinical trial of ultevursen for USH2A initiated in December of 2021.
The company is seeking a partner to take on its programs for sepofarsen, ultevursen, and an additional program for retinitis pigmentosa. ProQR will continue to provide access to sepofarsen and ultevursen for patients in the Phase 2/3 clinical trials.
ProQR’s decision to wind down the sepofarsen and ultevursen programs was based on conserving cash for the development of its Axiomer® RNA-editing platform technology for targeting other therapeutic areas, including the liver and central nervous system.
“ProQR’s decision to end development of its RNA therapies for retinal diseases is difficult news, but the Foundation recognizes the progress the company has made in advancing the field to date,“ said Jason Menzo, CEO of the Foundation Fighting Blindness. “We are committed to help the company find a new partner and optimistic about the future prospects of these programs to address the many affected by these conditions.”
ProQR’s RNA therapies are known as antisense oligonucleotides (AONs) — small pieces of genetic material that can bind complementary molecules of messenger RNA (mRNA) — designed to mask mutations in the mRNA of the affected gene. RNA are genetic messages that cells read to make proteins critical to their health and function.
The Foundation Fighting Blindness has a partnership agreement for the development of ultevursen through its venture arm, the RD Fund, for advancing emerging therapies in or approaching clinical trials.
]]>The RD Fund (Retinal Degeneration Fund), the venture philanthropy arm of the Foundation Fighting Blindness, has invested in SalioGen Therapeutics, a biotechnology company developing therapies for a broad range of conditions, including inherited retinal diseases, using its novel Gene CodingTM technology.
SalioGen has received a total of $115 million in a Series B round of financing to enable the company to continue building out the Gene Coding platform, expand the company’s team, and establish manufacturing and automation capabilities critical for accelerating the advancement of its preclinical programs. In March 2021, the company received $20 million in Series A funding.
SalioGen’s Gene Coding platform works by adding new genomic code to turn on, off, or modify function of new or existing genes. Gene Coding is accomplished by SalioGen’s Exact DNA Integration TechnologyTM (EDITTM), which is based on mammal-derived genome engineering enzymes called SaliogaseTM. Saliogase seamlessly inserts new DNA of any size into precise, defined genomic locations.
SalioGen’s technology is designed to be more efficient and reliable than other gene-editing and gene-modifying approaches (e.g., CRISPR/Cas9) because it doesn’t involve the double-stranded break and subsequent repair (a process called homologous recombination) of the targeted gene.
Furthermore, the company is developing targeted lipid-based nanoparticle formulations to deliver the therapy and its genetic cargo, DNA of virtually any size. In contrast, current viral delivery systems for gene-augmentation therapies are limited in the size of the genetic cargo they can deliver. Many retinal disease genes are too big for the viral containers used in these systems.
The company is currently developing research- and preclinical-stage programs and aims to launch future clinical trials for treatments for Stargardt disease (ABCA4), Usher syndrome, RP25 (EYS), and RP1.
“We are excited by SalioGen’s promising and innovative technology for addressing the genetic causes of inherited retinal disease. Their approach overcomes many of the limitations with current gene augmentation therapies and CRISPR/Cas9 gene editing,” says Benjamin Yerxa, PhD, chief executive officer, Foundation Fighting Blindness. “Our investment will help the company advance their emerging therapies into clinical trials. That is an important goal for the Foundation and the RD Fund.”
The Foundation established the RD Fund in 2018 to make mission-related investments in companies with projects nearing clinical trials. Visit RDFund.org for more information.
]]>ProQR, a developer of RNA therapies in the Netherlands, has dosed the first patients in its Phase 2/3 Sirius and Celeste trials for QR-421a, an RNA therapy for people with mutations in the exon 13 region of the USH2A gene. These mutations cause Usher syndrome type 2A (USH2A) or non-syndromic retinitis pigmentosa (RP). According to ProQR, more than 16,000 people in the Western world have USH2A or RP caused by these mutations.
“We are excited to see ProQR’s QR-421a RNA therapy move into Phase 2/3 trials, thanks to vision improvements observed in the Phase ½ trial,” says Benjamin Yerxa, PhD, chief executive officer, Foundation Fighting Blindness. “The Phase 2/3 trials, if successful, could lead to regulatory approval of QR-421a, potentially making it available to thousands of people affected by RP and Usher syndrome type 2A.”
The Foundation Fighting Blindness invested $7.5 million through its RD Fund to move QR-421a into and through the Phase ½ clinical trial. The RD Fund, a venture philanthropy fund, was established in 2018 to provide investments for promising retinal degenerative disease therapies that are in, or moving toward, early human studies.
QR-421a is an antisense oligonucleotide (AON) — a small piece of genetic material — designed to mask exon 13 mutations in the RNA derived from the USH2A gene. RNA are genetic messages that cells read to make proteins critical to their health and function. QR-421a enables retinal cells to skip over exon 13 (and any mutations inside it) when reading the USH2A RNA, enabling the cells to make functional protein that will hopefully halt or slow the disease process and vision loss.
Both Sirius and Celeste trials are for people 12 and older. In both studies, participants are randomly assigned to three parallel study arms. In the two treatment arms, participants receive intravitreal injections with QR-421a at different doses. In the third sham/control arm, the intravitreal injections are mimicked, but no injection or study medication is given.
The Sirius study will enroll 81 participants with advanced vision loss — those with baseline best corrected visual acuity (BCVA) of worse than 20/40 as measured using an eye chart. The primary endpoint in the study is mean change from baseline in BCVA at 18 months in the treated arms compared to the sham/control arm.
The Celeste study will enroll 120 participants with early to moderate vision loss (baseline BCVA equal to or better than 20/40). The primary endpoint in the study is the mean change from baseline in static perimetry at 12 months in the treated arms compared to the control arm. Static perimetry measures retinal sensitivity at different points in the patient’s visual field.
In the Phase ½ Stellar trial, QR-421a demonstrated benefits in BCVA, static perimetry, and retinal structure as measured by optical coherence tomography (OCT). Improvements in BCVA were greatest for the six treated patients with advanced disease. Improvements in perimetry were greatest for the eight treated patients with early-moderate disease. All 14 treated patients received one dose of QR-421a, and results were reported at 48 weeks after treatment.
]]>[[quote-right “Usher syndrome type 1B is a particularly challenging condition on many fronts. While we have made progress in understanding the disease and investigating numerous therapeutic prospects, there’s clearly much more work that needs to be done.” “José-Alain Sahel, MD”]]
The meeting was co-chaired by José-Alain Sahel, MD, University of Pittsburgh Medical Center and the Institut de la Vision in Paris, and Shannon Boye, PhD, University of Florida and Atsena Therapeutics.
“Usher syndrome type 1B is a particularly challenging condition on many fronts. While we have made progress in understanding the disease and investigating numerous therapeutic prospects, there’s clearly much more work that needs to be done,” said Dr. Sahel. “The workshop was an important step in determining the necessary actions to get us closer to validating effective therapies and engaging all the partners, especially the patients and their families.”
Usher syndrome is a devastating diagnosis — it’s an inherited condition causing combined vision and hearing loss, and potentially problems with balance. The disease affects about 25,000 people in the US and 400,000 worldwide. USH1B is the most severe form of Usher syndrome causing profound hearing loss at birth and progressive vision loss and balance problems. Approximately 40 percent of people with Usher syndrome have USH1B.
Patient Perspectives
“Imagine having to navigate the world blind, deaf, and without balance. USH1B is an assault on the primary senses. We’re not just fighting the early unmet and rapid progression of vision loss, we’re also battling congenital deafness and severe balance issues,” said Justin Porcano, a workshop participant whose three-year-old daughter has USH1B. “The workshop was a critical step in the right direction for understanding the gaps in research for this underserved disorder, but what we do next is what really matters.”
Usher syndrome was the last thing that Justin and Rosalyn Porcano expected for their daughter, Lia, when she was born in March 2018. But Lia failed her hearing test when she was just 12 hours old. Two weeks later, they learned Lia was completely deaf. In August, results from genetic testing revealed that the Porcano’s daughter had USH1B and would progressively lose vision, as well. They were devastated and frightened. During the workshop, Justin said how “a lack of control to help my child” was so incredibly difficult for him and his wife. But the Porcanos quickly took action and founded Save Sight Now, a nonprofit to raise money for USH1B research funded by the Foundation Fighting Blindness. They raised $285,000 in their first year.
Twenty-four-year-old David Applegate from Portland, Oregon, expressed his urgent need for a treatment. “I’ve been plagued with the fear of losing my independence right at the time when I’m on the cusp of moving out. I want more than anything to be able to make my own way in life, to have a family and a path of my own, and it constantly feels like those dreams are hanging in the balance,” he said.
Maryrose Sylvester, a Foundation Board Vice Chair, and Steve Browne, a Foundation National Trustee, also spoke compellingly about their daughters’ challenges with USH1B and the urgent need for a treatment to address their progressive vision loss.
Todd Durham, PhD, senior VP of clinical outcomes research at the Foundation, reported survey results for USH1B patients and caregivers identified through the My Retina Tracker Patient Registry and other patient networks. Among the results: 42 of 78 respondents said that loss of vision and ultimately blindness was their biggest worry. Also, the top three motivations for participating in a clinical trial (58 respondents) were: 1) stopping vision loss progression, 2) improving lost vision, and 3) finding a cure.
The MYO7A gene
Claire Gelfman, PhD, the Foundation’s chief scientific officer, and Aziz El-Amraoui, PhD, Institut Pasteur, reviewed the roles of the protein expressed by the MYO7A gene, which when mutated, causes USH1B.
MYO7A plays an important role in the health and function of photoreceptors and retinal pigment epithelial cells in the retina, as well as in hair cells in the cochlea of the inner ear. In the retina, MYO7A is a protein expressed in both rod and cone photoreceptors, the cells that make vision possible, and retinal pigment epithelial cells which support the photoreceptors.
Researchers have determined that MYO7A helps other proteins, molecules, and organelles move through cells, so that cells remain healthy and function properly. MYO7A also helps retinal cells maintain their shape. Serge Picaud, PhD, Institut de la Vision, said he believes that MYO7A also enables photoreceptors to orient properly.
USH1B challenges
Animal models: Retinal researchers frequently use rodent models for evaluating therapies. The USH1B mice with mutations in the MYO7A gene experience hearing defects (not unlike those seen in people with USH1B), but interestingly, don’t have vision loss. Researchers believe this is because the rodents lack calyceal processes, which act like a girdle in the middle of the photoreceptor, where the sensory part of the cell (outer segment) connects with the cell body (inner segment).
Hannah Nonarath, Medical College of Wisconsin, presented her work in USH1B zebrafish and David Gamm, MD, PhD, University of Wisconsin-Madison, discussed his development of human USH1B retinal organoids derived from induced pluripotent stem cells. While both models are helpful in understanding USH1B, they have limitations in their relevance to humans. For example, zebrafish have tiny eyes, much smaller than humans. And, retinal organoids are not fully developed retinas nor are they part of a complete eye system.
The Foundation is funding Martha Neuringer, PhD, Oregon Health & Science University, to develop a non-human primate model of USH1B, which, if successful, would closely resemble humans with USH1B. That work is in progress.
David Williams, PhD, University of California Los Angeles, Jacque Duncan, MD, University of California San Francisco, and Joseph Carroll, PhD, Medical College of Wisconsin are collaboratively developing a pig model of USH1B which also has the potential to closely resemble the human disease. That work is also in progress.
The animal models under development will help researchers learn more about the development of USH1B and its effect on both vision and hearing, as well as provide a higher species animal model for the testing of potential therapeutics.
Large size of MYO7A gene: Adeno-associated viruses (AAVs) are the gene delivery systems commonly used in emerging gene augmentation therapies, as well as in the FDA-approved retinal gene therapy, LUXTURNA. AAVs have a cargo capacity of 4.7 kb. However, the MYO7A gene is 6.6 kb, so standard AAV systems won’t work. Atsena Therapeutics and TIGEM are currently developing dual vector AAVs to deliver MYO7A in two containers (more on these approaches below), which would facilitate the delivery of the larger transgene size.
Natural history and clinical trial endpoints: While some natural history studies have been conducted for USH1B, more knowledge is needed about the rate and nature of disease progression so that researchers can understand the best windows for treatment and which outcome measures will be optimal for clinical trials of emerging therapies.
Mark Pennesi, MD, PhD, Oregon Health & Science University, said that the clinical research community needs to work closely with the FDA to identify endpoints that are better suited for clinical trials of therapies for Usher syndrome and related conditions.
Emerging Therapies
Dual vector gene therapies: To overcome the challenge of delivering the large MYO7A gene into retinal cells via gene augmentation therapy, both Alberto Auricchio, MD, at the Telethon Institute of Genetics and Medicine (TIGEM), and Shannon Boye, PhD, of Atsena Therapeutics and University of Florida, presented their dual-AAV vector approaches for delivering the MYO7A gene to retinal cells. Both of these approaches involve delivery of the gene in two containers — the front half in one container and the back half in another. When the two halves arrive in the cells, they join together through a natural process called homologous recombination to make the full-length gene so that the full-length protein can be produced.
AAVantgarde Bio, co-founded by Dr. Auricchio, is planning to begin enrollment for a Phase ½ clinical trial of their dual-vector approach for USH1B in April 2022.
Atsena Therapeutics, co-founded by Dr. Boye and funded through the Foundation’s RD Fund, has made significant progress in developing a safe and effective dual vector AAV therapy, having evaluated dozens of different constructs. The company is close to selecting a lead candidate, and from there will move into IND-enabling studies for launching a clinical trial.
Dr. Boye noted that while both companies are developing dual-vector gene therapy approaches which apply homologous recombination, they are technically different.
Dr. Boye added, “Alberto and I have known each other for a long time and we both see the value of collaborating in a precompetitive space. It’s what helps get these treatments over the finish line more quickly.”
[[quote-left “While the Foundation is focused on emerging therapies that directly address USH1B, we are also encouraged by the progress being made in our investments in gene-agnostic approaches, like those from Nacuity and SparingVision, which are in, or approaching, clinical trials.” “Benjamin Yerxa, PhD, CEO, Foundation Fighting Blindness”]]
NACA small molecule: Nacuity Pharmaceuticals’ Halden Conner, MBA, and Jami Kern, MBA, PhD, reviewed the Phase ½ clinical trial in Australia for the antioxidative molecule NACA being developed by their company. Initiated in January 2020, the 24-month study is enrolling 48 participants with Usher syndrome (all forms). The company will report six-month results in the last quarter of 2021 and 12- and 18-month results in 2022. A clinical trial for retinitis pigmentosa is planned in the US and Australia in 2022.
The oral, gene-agnostic drug is designed to slow vision loss by reducing oxidative stress.
Headquartered in Dallas, Nacuity is funded through the Foundation’s RD Fund.
“While the Foundation is focused on emerging therapies that directly address USH1B, we are also encouraged by the progress being made in our investments in gene-agnostic approaches, like those from Nacuity and SparingVision, which are in, or approaching, clinical trials,” said Benjamin Yerxa, PhD, the Foundation’s chief executive officer. “These have the potential to preserve vision for a broad range of retinal disease patients, including those with USH1B.”
]]>Early, encouraging results from two human studies — trials launched by Bionic Sight and GenSight — are putting optogenetic therapies in the spotlight for patients with advanced vision loss (i.e., only light perception) from retinal conditions such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD).
In the Bionic Sight trial, investigators reported that the first four RP patients dosed can now see light and motion. Two of the patients can detect the direction of motion; that is, they can determine if objects are moving to the right or left. One patient said that one of the first new things he saw was Hanukkah candles on the eighth day of the holiday when they were all lit. Also, two patients who practice martial arts saw the robes of their opponents against the dark blue mat.
GenSight reported results for a 58-year-old man who entered the trial with only light perception due to advanced RP (Usher syndrome type 2A). After receiving the optogenetic therapy, the patient was able to locate and reach for objects on a table while wearing the image-capturing eyewear. Results from the GenSight trial were reported in the journal Nature Medicine. The Foundation funded lab research that led to initiation of the GenSight study.
In simple terms, optogenetic treatments bestow light sensitivity to cells that normally don’t respond to light or cells that have lost their light-sensing ability. And, they’re gene-agnostic, designed to work independent of the mutated gene causing the patient’s retinal disease.
The emerging therapies from Bionic Sight and GenSight are designed to enable retinal ganglion cells to respond to light, so they can work like a back-up system for photoreceptors, the cells that normally make vision possible. Ganglion cells often survive after photoreceptors are lost to advanced retinal disease. In both treatments, copies of an algae-derived gene that express a light-sensing protein are delivered to the ganglion cells. Both approaches use viral gene delivery systems and include eyewear to enhance the visual information sent to the retinas.
Nanoscope Therapeutics recently launched a clinical trial in the US for its optogenetic therapy, which involves viral delivery of a light-sensitive gene (a multi-characteristic opsin) to bipolar cells in the retina. The company will enroll 27 people with advanced RP in its trial.
An emerging protein-based optogenetic approach being developed by Vedere Bio and funded by the Foundation’s RD Fund was recently acquired by Novartis. After the acquisition, Vedere Bio II was launched to develop another optogenetic therapy.
Two groups are working on optogenetic therapies designed to resurrect dormant cone photoreceptors in people with advanced retinal disease. One of the groups, SparingVision, is funded through the RD Fund. The other group is led by Hendrik Scholl, MD, Institute of Molecular and Clinical Ophthalmology Basel, and funded by the Foundation’s Translational Research Acceleration Program (TRAP).
Keep in mind that while there is much promising research activity for optogenetic therapies, the approach is still at an early stage of clinical development; there is much that the research community is learning about the potential for meaningful, natural vision restoration from optogenetics.
]]>GenSight’s treatment combines a light-sensing gene therapy (optogenetics) coupled with image-capturing eyewear, which enhances visual stimulation. The optogenetic therapy is designed to bestow light sensitivity to ganglion cells — retinal cells that are not normally light sensitive, but often survive after photoreceptors are lost. The eyewear transmits an amplified light image signal to further stimulate ganglion cells and enhance the user’s visual experience.
[[image-right 1319]] The system is designed to restore vision for people who are blind from advanced RP and potentially other retinal conditions such as: Usher syndrome, Stargardt disease, and dry age-related macular degeneration. The GS030 system works independent of the gene mutation causing the retinal disease.
GenSight reported results for a 58-year-old man who entered the trial with only light perception due to advanced RP (Usher syndrome type 2A). After receiving the optogenetic therapy, the patient was able to locate and reach for objects on a table while wearing the image-capturing eyewear. Also, using electroencephalography, a technique that maps neural connections between the eye and the brain, the clinical researchers observed increased activity in the patient’s visual cortex while he was undergoing the tests to perceive objects.
As of the end of 2020, seven patients in the PIONEER dose-escalation trial had received the emerging optogenetic treatment. However, due to the COVID-19 pandemic, visual assessment was only performed on one patient. He received the lowest dose of the optogenetic treatment.
“We are encouraged by the initial report of partial vision restoration coming from GenSight’s trial for its optogenetic therapy and look forward to more data from additional patients,” says Ben Yerxa, PhD, chief executive officer at the Foundation Fighting Blindness. “Optogenetics is exciting for us because it provides a potential solution for people with the most advanced vision loss.”
]]>To launch an authorized clinical trial, a therapy developer must submit an Investigational New Drug (IND) application to the US Food & Drug Administration (FDA) – a process that requires expensive preclinical studies, regulatory knowledge, and manufacturing expertise. TRAP-funded grants support these efforts and guides projects toward an IND submission.
“Our TRAP grantees are exceptional scientists developing therapies that have strong potential to reach the patients with retinal diseases who need them,” says Chad Jackson, PhD, director of the Foundation’s TRAP program. “Translational research is challenging and expensive, but our program gives these scientists critical resources to help them succeed.”
Summaries of the new TRAP grants:
Dry AMD Gene Therapy
Bärbel Rohrer, PhD, Medical University of South Carolina, is conducting an animal study of a gene therapy designed to selectively deliver a component of complement factor H (CFH) to temper the overactive innate immune system in age-related macular degeneration (AMD). The approach is designed to mitigate retinal degeneration caused by the immune response, targeting the damage where it is most likely to occur.
Pharmaceutical for RP
Paul Yang, MD, PhD, is evaluating the drug mycophenolate as a therapy for multiple forms of RP and related conditions. Already approved by the FDA for inflammatory conditions, mycophenolate has been shown to reduce the accumulation of a molecule called cyclic guanosine monophosphate (cGMP). While cGMP is an important messenger molecule for converting light into electrical signals in the retina, too much of it is toxic and causes retinal degeneration.
Small-Molecule for Usher Syndrome 3A (USH3A)
Mahdi Farhan, MD, Usher 3 Initiative, is completing pre-IND toxicity studies to advance a novel small-molecule therapy for USH3A into a Phase 1 clinical trial. The emerging drug works by stabilizing the misfolded USH3A protein (clarin-1) and enabling it to better move to its target location in retinal cells, thereby striving to preserve structure and function.
Enabling the Retina to Generate New Photoreceptors
Tom Reh, PhD, University of Washington, is developing a process to enable the human retina to grow its own new photoreceptors. Thus far, he has used a small molecule to sprout photoreceptors from Muller glia in mice. The TRAP project is for evaluating the approach in a large animal.
Cross-Cutting Gene Therapy for RP
Stephen Tsang, MD, PhD, Columbia University, is developing a gene therapy to increase aerobic glycolysis – a process that generates energy – in cone photoreceptors of those affected by retinitis pigmentosa (RP). He believes the approach may preserve cones for RP patients and would do so independent of the mutated gene causing the disease.
RNA Therapies for Stargardt Disease
Rob Collin, PhD, Radboud University, is developing antisense oligonucleotides (AON) – tiny pieces of DNA – to mask splicing mutations in ABCA4, the affected gene in people with Stargardt disease. The AONs target mutations in RNA, the genetic messages used to build proteins that are necessary for a cell’s health and proper functioning.
Restoring Dormant Retinal Cell Function
Hendrik Scholl, MD, Institute of Molecular and Clinical Ophthalmology Basel, is developing an optogenetic therapy to restore function to dormant cone photoreceptor cells for potentially a broad range of inherited retinal diseases. Cones are responsible for high-acuity, daytime vision, and in a certain percentage of patients, remain in a dormant state. This effort will perform late-stage preclinical studies that are required to start the first-in-human cone-based optogenetic vision restoration clinical trial. This optogenetic therapy produces a protein that makes dormant cone cells sensitive to light.
]]>ProQR, a developer of RNA therapies in the Netherlands, has reported improvements in vision and retinal structure for patients in its Phase ½ Stellar clinical trial for QR-421a, an RNA therapy for people with mutations in exon 13 of the USH2A gene. These mutations cause Usher syndrome type 2A (USH2A) or non-syndromic retinitis pigmentosa (RP). According to ProQR, more than 16,000 in the Western world have USH2A or RP caused by these mutations.
As a result of these findings, ProQR is planning two Phase 2/3 trials for QR-421a. Both trials are expected to start by the end of 2021. The Sirius trial will enroll approximately 100 patients with advanced vision loss. The Celeste trial will enroll approximately 100 patients with early-moderate vision loss.
“We are very pleased to see these results for QR-421a in ProQR’s Phase ½ trial and the company’s plans for Phase 2/3 studies by the end of the year,” says Benjamin Yerxa, PhD, chief executive officer, Foundation Fighting Blindness. “With its LCA-CEP290 treatment in a Phase 2/3 trial, ProQR is demonstrating well that its RNA therapies have encouraging potential for people with inherited retinal diseases.”
The Foundation Fighting Blindness invested $7.5 million through its RD Fund to move QR-421a into and through the early stage clinical trial. The RD Fund, a venture philanthropy fund, was established in 2018 to provide investments for promising retinal degenerative disease therapies that are in or moving toward early human studies.
QR-421a is an antisense oligonucleotide (AON) — a small piece of genetic material — designed to mask exon 13 mutations in the RNA of USH2A. RNA are genetic messages that cells read to make proteins critical to their health and function. QR-421a enables retinal cells to skip over exon 13 (and any mutations inside it) when reading the USH2A RNA, enabling the cells to make functional protein that will hopefully halt or slow the disease process and vision loss.
In the Phase ½ Stellar trial, QR-421a demonstrated benefits in best corrected visual activity (BCVA); static perimetry, which measures light sensitivity in the peripheral retina; and retinal structure as measured by optical coherence tomography (OCT). Improvements in BCVA were greatest for the six treated patients with advanced disease. Improvements in perimetry were greatest for the eight treated patients with early-moderate disease. All 14 treated patients received one dose of QR-421a, and results were reported at 48 weeks after treatment. Based on observations of durability, retreatment at 24 weeks is believed to be optimal.
]]>The Foundation Fighting Blindness is investing $3 million in Atsena Therapeutics, a newly formed company with three retinal disease gene therapies in development. The first is for Leber congenital amaurosis (LCA) caused by mutations in GUCY2D, which is in a Phase ½ clinical trial at the University of Pennsylvania. The second, in preclinical studies, is a dual-vector gene therapy for Usher syndrome type 1B (USH1B) which is caused by mutations in MYO7A. The third program, also in preclinical studies, will be disclosed in the coming months.
[[quote-left “Shannon Boye has emerged as a leading innovator of gene therapies for inherited retinal diseases. Her advancements are having tremendous impact in the field.” “Benjamin Yerxa, PhD, chief executive officer, Foundation Fighting Blindness”]]
Atsena Founder and Chief Scientific Officer Shannon Boye, PhD, University of Florida, is the preclinical developer for the company’s emerging gene therapies. Founder Sanford Boye, MSc, University of Florida, serves as the company’s chief technology officer.
“Shannon Boye has emerged as a leading innovator of gene therapies for inherited retinal diseases. Her advancements are having tremendous impact in the field,” says Benjamin Yerxa, PhD, chief executive officer, Foundation Fighting Blindness. “We are delighted to see the Foundation’s investment in her research over the past 15 years lead to the formation of Atsena and its promising gene therapies for saving vision.”
“Sustained support from the Foundation Fighting Blindness throughout my career has been crucial for advancing multiple preclinical programs in my lab,” says Dr. Boye. “And now, the Foundation’s funding is actually helping us get treatments into clinical trials. I am extremely excited by our potential now to save and restore vision in patients affected by these challenging retinal diseases. I am also genuinely heartened by the team we’ve built at Atsena, their universal desire to put patients first, and my ability to advance these therapies along with my FFB ‘family’.”
The Foundation’s investment in Atsena is being made through its RD Fund, a venture philanthropy fund for emerging therapies that are approaching, or in, early-stage clinical trials. The RD Fund was launched in 2018 with an initial investment of $70 million. The fund currently has eight projects in its portfolio.
Atsena’s Phase ½ gene therapy clinical trial for GUCY2D-LCA1 is being led by Samuel Jacobson, MD, PhD. While the primary goal of the early stage trial is to evaluate safety, investigators will also be evaluating changes in retinal function and structure.
LCA is a severe retinal disease causing vision loss in young children. More than two dozen genes, when mutated, can each cause LCA. LCA1, caused by GUCY2D mutations, is a common form of LCA, accounting for about 20 percent of cases.
Atsena’s dual adeno-associated virus (AAV) delivery system for USH1B addresses the challenge of delivering large genes — those too large to fit within a single AAV capsid— into retinal cells.
Usher syndrome is a leading cause of combined vision and hearing loss. More than a dozen genes when mutated can each cause the condition. MYO7A-USH1B is a relatively common form, accounting for about 25 percent of cases.
With Atsena’s dual AAV vector system, the MYO7A gene is split in half. Each half is delivered by a separate AAV vector and once both halves are delivered to the retina, they re-assemble to form the full length gene. While Atsena is working on delivery of MYO7A, the dual AAV vector system may ultimately be used to deliver other large retinal genes including, but not limited to, ABCA4 (Stargardt disease) and CEP290 (LCA).
Dr. Boye’s opening address for the Foundation’s 2020 VISIONS Conference, held virtually, reviewed both the LCA-GUCY2D and USH1B projects.
]]>Fort Worth-based Nacuity Pharmaceuticals is launching a Phase ½ clinical trial in Australia for NPI-001, an oral treatment designed to slow vision loss in people with retinitis pigmentosa (RP) and RP associated with Usher syndrome. The trial, known as SLO-RP (Safety and Efficacy of NPI-001 Tablets versus PLacebO for Treatment of Retinitis Pigmentosa associated with Usher Syndrome) will enroll at least 48 patients with Usher syndrome and follow them for two years. If results for SLO-RP are favorable, Nacuity plans to launch clinical trials of NPI-001 for people with RP in the US and Australia in 2021.
The Foundation is investing $7.5 million in NPI-001 development through its RD Fund, a venture philanthropy fund for emerging therapies that are approaching, or in, early-stage clinical trials. The Foundation is also providing scientific consulting for the clinical trial and therapy development. Benjamin Yerxa, PhD, chief executive officer at the Foundation, is on Nacuity’s board of directors. Rusty Kelley, PhD, vice president of investments at the Foundation, is a board observer for Nacuity.
“We are grateful to have the Foundation’s support and guidance to advance our emerging treatment into human studies, and hopefully, to patients with retinal diseases who need it,” says Halden Conner, chief executive officer and president at Nacuity. “With the Foundation as a partner, we feel well-poised to achieve our goals of getting NPI-001 across the finish line.”
NPI-001, a GMP-grade of N-acetylcysteine amide (NACA), is an experimental antioxidant drug. Researchers believe that increased oxidative stress plays a major role in retinal degeneration and vision loss across many inherited retinal diseases. Antioxidative therapies are designed to mitigate oxidative stress.
NACA is related to N-acetylcysteine (NAC), an FDA-approved antioxidant treatment for hepatotoxicity caused by acetaminophen overdose. However, NPI-001, which is manufactured using Nacuity’s patented process, is better able to penetrate retinal cells than NAC.
In Foundation-funded lab studies at Johns Hopkins University, NPI-001 reduced oxidative stress and preserved vision.
“Nacuity’s emerging therapy is based on very thoughtful and sound science. Because it is a tablet taken orally, dosing can be easily adjusted,” says Dr. Yerxa. “Furthermore, it is designed to work independent of the mutated gene causing the recipient’s vision loss. That means NPI-001 has the potential to help many people with a wide range of diseases and genetic profiles.”
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But like the career paths of most researchers, Shannon’s journey in the science field has been lifelong and marked by a variety achievements, setbacks, and unexpected epiphanies.
“Throughout my life, I’ve always gravitated towards science and art. But it wasn’t until AP biology class in high school with Mrs. Cindy Richards that I fully embraced my inner science nerd,” says Shannon. “I went to an all-girls Catholic school, and we didn’t have super fancy lab equipment, but Mrs. Richards always made it interesting and exciting. My favorite lesson ever was given during OJ Simpson’s murder trial. We learned about DNA fingerprinting and how biological evidence from a crime scene could be linked to a suspect. I remember looking at the bands on the gel thinking, ‘he totally did it’.”
A marine biology fanatic, Shannon chose the field as her college major. “The coolest part of the program” for her was quantifying juvenile fish populations on tropical coral reefs at the University of Hawaii. In between her junior and senior years, she was accepted into the Research Experience for Undergraduates (REU) program at the Whitney Marine Lab, an offshoot of the University of Florida (UF).
“I spent my summer at REU dissecting mosquito guts, of all things. My mentor, Dr. Paul Linser, was super fun and engaging,” recalls Shannon. “While he wasn’t writing grants or playing guitar, he was pushing me to apply to graduate school. After a visit to UF’s main campus that summer, I was sold. And the rest is history.”
As a neuroscience graduate student at UF, she didn’t realize it at the time, but she was in a gene therapy mecca. “The scientists who had made some of the seminal discoveries in the field were right down the hall. Some of the very first clinical trials using adeno-associated viruses or AAVs to address inherited disease were taking place in our hospital.”
The road ahead for Shannon had formidable obstacles, especially given she was a young woman starting her career at the same institute she’d been a student, in a male-dominated field. She recalls, “I crossed paths with professors who said I could not do it, who told me I ‘wasn’t too big to fail’ after I got a grant, and who took credit for my ideas. In the beginning, this led to tears. But, I am grateful for those moments because they thickened my skin. At 40 years old, I now recognize this type of aggression means I’m doing something right. It’s actually empowering.”
With her own lab now, Shannon serves as the mentor for several young students, guiding them through the tough moments. “Adversity comes in a variety of forms. Setbacks in research are the norm. Now, I have to coach my students through those tears,” she says.
Shannon is especially fond of a quote on adversity from Winston Churchill who said, “Success is not final, failure is not fatal, it is the courage to continue that counts.”
In addition to running her own lab, Shannon is ever-present as a speaker at Foundation events. She has a special talent for communicating research in a way that non-scientists can understand. But she also takes part in these activities as a way of paying her success forward to the Foundation and its constituents.
“The Foundation has been instrumental in launching my career and funding much of my research, including my LCA1-GUCY2D and dual-vector projects,” she says. “The support has helped us get the LCA1-GUCY2D gene therapy into a clinical trial at the University of Pennsylvania. And, we are now funded by the Foundation for the studies to advance a dual-vector gene therapy for Usher 1B (MYO7A) into a human study.”
Shannon also says that her success wouldn’t have been possible without her husband, Sanford Boye. “I consider him my secret weapon and he considers me his, which is why I think we work so well together. Science is a team sport, and our partnership is a crucial part of the machine. He also baits my hooks when we go fishing, so he’s a keeper!”
]]>ProQR Therapeutics, an RNA therapy developer in the Netherlands, has announced three-month, interim Phase ½ clinical trial results for QR-421a, an emerging treatment for people with Usher syndrome type 2A and non-syndromic retinitis pigmentosa (RP) caused by mutations in exon 13 of the USH2A gene. The company reported that the treatment was well tolerated and caused no serious adverse events. Also, 25 percent of patients receiving the treatment demonstrated improved vision.
In its news release, ProQR reported, “One of four treated patients in the low-dose group was classified as a responder, with onset of action observed by the three month visit. Benefit was maintained for six months or longer.” The positive response to the treatment was observed in both functional and structural measures. The responder in the low-dose group has Usher syndrome.
[[quote-left “We are encouraged to see a favorable safety profile for the QR-421a trial as well as suggestions of improvement across three independent outcome measurements in each of the two responders. We look forward to further results to elaborate more on the initial efficacy signals.” “Brian Mansfield, PhD, executive vice president of research and interim chief scientific officer, Foundation Fighting Blindness”]]
The news release also said, “One of four treated patients in the mid-dose group was classified as a responder with onset of action observed by three months.” The positive response to the treatment was observed in several functional measures. The responder in the mid-dose group has advanced vision loss from non-syndromic RP.
The Foundation Fighting Blindness is investing up to $7.5 million through its RD Fund to move QR-421a into and through the early stage clinical trial. The RD Fund, a venture philanthropy fund, was established in 2018 to provide investments for promising retinal degenerative disease therapies that are in, or moving toward, early human studies.
“We are encouraged to see a favorable safety profile for the QR-421a trial as well as suggestions of improvement across three independent outcome measurements in each of the two responders,” says Brian Mansfield, PhD, executive vice president of research and interim chief scientific officer at the Foundation Fighting Blindness. “We look forward to further results to elaborate more on the initial efficacy signals.”
QR-421a is an antisense oligonucleotide (AON) — a small piece of genetic material — designed to mask exon 13 mutations in the RNA of USH2A. RNA are genetic messages that cells read to make proteins essential to their health and function. QR-421a enables retinal cells to skip over any mutation inside a region of the RNA called exon 13 when reading the USH2A RNA, enabling the cells to make functional protein that will hopefully halt or slow the disease process and vision loss. The treatment is administered through intravitreal injections.
]]>The Foundation Fighting Blindness, in partnership with Blueprint Genetics and InformedDNA, offers no-cost genetic testing and counseling to people affected by the entire spectrum of inherited retinal diseases (IRDs) including retinitis pigmentosa (RP), Usher syndrome, and Stargardt disease. The test is available to those clinically diagnosed with an IRD living in the US or US territories (Puerto Rico, the commonwealth of the Northern Mariana Islands, Guam, American Samoa, and the US Virgin Islands: St. Thomas, St. Croix, St. John).
Why genetic testing for IRDs?
Eye care professionals make a clinical diagnosis of an IRD by examining a patient’s retinas. While a clinical examination provides critical information about the retinal condition, Identifying the IRD-causing gene mutations through genetic testing can provide more diagnostic information. In fact, studies have shown that clinical diagnoses change in about 15 percent of cases after genetic testing.
Identifying the disease-causing gene mutation(s) not only can provide more detail of a diagnosis, it can help a patient better understand the risk for other family members (siblings, children, etc.) for inheriting the IRD. Also, knowing one’s IRD gene mutation(s) can help them qualify for a clinical trial for an emerging therapy, many of which are now gene- or mutation-specific.
Why the Blueprint Genetics testing panel?
The Blueprint panel provides high-quality, broad, and deep testing for IRD genes. The panel screens 285 genes and includes the gene RPGR, a relatively common IRD gene, which when mutated causes X-linked RP. (Other panels may not test for the complete RPGR gene) The Blueprint panel also can identify hard-to-find mutations (i.e., intronic and copy-number variants), which other panels may not screen for.
Furthermore, Blueprint Genetics and its partners, the Foundation Fighting Blindness and InformedDNA, will never release a person’s personal information. A person’s privacy is always protected. With other IRD genetic tests, the patient’s personal information may be released.
The test ordering process
Tests can only be ordered by a clinician. The testing company, Blueprint Genetics, cannot take test orders directly from patients.
Any doctor in the US who is able to clinically diagnose a patient with an IRD can order the test online from Blueprint Genetics through the company’s Nucleus portal, which is available at www.BlueprintGenetics.com.
Patients with IRDs should contact their doctor and ask him or her to order the test. Doctors need to select the My Retina Tracker Program Panel to order the genetic test. Patients who have questions about testing or the program should contact their doctor. The test itself is simple; the clinician only needs to collect a saliva or blood sample from the patient. Patients should not contact Blueprint Genetics.
What to expect
Once a saliva sample is submitted to Blueprint Genetics, the test results are sent to the doctor in about four weeks. The results are conclusive in about 60-65 percent of cases. Whether the results are conclusive or not, the genetic counselor will help the patient understand what the results mean and potential next steps for the patient and family. Keep in mind that many emerging IRD therapies are designed to work independent of the mutated gene. So, while knowing one’s IRD gene is helpful in disease management, there are emerging treatment options for those who haven’t had their gene identified.
Why genetic counseling?
A genetic counselor helps patients and families understand what the genetic test results mean, what research (including clinical trials) may be relevant, the IRD inheritance pattern, and potential next steps. InformedDNA has extensive knowledge and experience in the IRD space and provides comprehensive, telephone-based genetic counseling to patients and families. The counseling session is typically 60-75 minutes.
The My Retina Tracker Registry
Any patient with an IRD can register in the Foundation’s global, secure My Retina Tracker Registry (www.MyRetinaTracker.org) to share their disease information with researchers and companies, many of which are recruiting for clinical trials for emerging therapies. Only de-identified information is shared. Personal information is never shared. A patient’s privacy is always protected. (The Foundation notifies the patient if he or she matches the researcher’s or company’s search criteria and then it is up to the patient to contact the researcher or company.) While a person’s genetic profile is valuable information to include in their registry record, they do not have to know their IRD gene mutation(s) to register.
Additional resources
Why genetic testing is important
Open Access Genetic Testing Program
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]]>Many of the benefits of eye research are obvious. Good eye health, and saving and restoring vision from disease and injury, are critical to helping us live independently and perform the many activities that are part of our daily lives such as seeing the faces of friends and family, reading, and driving.
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What’s good for the eye is good for the brain
However, research efforts for the eye, especially the development of therapies for the retina, are having a major impact on the advancement of treatments for the brain and neurological diseases and conditions. The retina is also an extension of the brain; its neurons are much like the neurons in the brain and nervous system. The retina, a thin piece of tissue which lines the back of the eye, is comprised of sensory neural cells that enable us to see.
That means that a treatment that might save or restore retinal neurons — some of these are referred to as neuroprotective therapies — might also help people with neurological conditions such as Alzheimer’s disease, Parkinson’s disease, or multiple sclerosis. In fact, the disease processes that occur in the retina are in some cases similar to those that affect the brain. For example, the harmful beta-amyloid proteins found in the brains of those with Alzheimer’s disease also accumulate in the retinas of people with age-related macular degeneration, a retinal disease that’s the leading cause of blindness in people 50 years of age and older.
What makes the retina special?
For scientists, the retina is a particularly attractive target to initiate studies of therapeutic drugs and molecules that might ultimately have broad application to the brain and nervous system. The reasons are numerous:
A success story
In December 2017, a treatment known as LUXTURNA ™ became the first FDA-approved gene therapy for the eye or any inherited condition. Developed by Spark Therapeutics with preclinical support from the Foundation Fighting Blindness, the treatment has restored vision for children and young adults who were virtually blind from a genetic retinal disease called Leber congenital amaurosis. Thanks in part to the clinical success of LUXTURNA and other emerging retinal gene therapies, the number of gene therapy programs for all diseases has grown dramatically — from about 200 programs in 2014 to more than 700 in 2018 (source Pharma Intelligence Informa).
]]>On May 16, 2019, the Baltimore Chapter of the Foundation Fighting Blindness honored Donald Zack, MD, PhD, a world-renowned retinal researcher from Johns Hopkins University, Wilmer Eye Institute, at its Wine & Dine for Sight fundraiser.
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Dr. Zack, the Guerrieri Professor of Genetic Engineering and Molecular Ophthalmology and co-director of the Center for Stem Cells and Ocular Regenerative Medicine (STORM), began receiving Foundation funding in 1994 to identify sight-saving treatments for people with retinal diseases. He is also a member of the Foundation’s Scientific Advisory Board and chairs its Cellular Molecular Mechanisms of Disease study section.
On April 29, he received the 2019 Freidenwald Award for identifying compounds known as kinase inhibitors that demonstrate strong potential for inhibiting the cellular signals that lead to death of retinal ganglion cells and photoreceptors, the cells that make vision possible. The Foundation funded Dr. Zack for some of this research, which may benefit people with glaucoma and inherited retinal diseases like retinitis pigmentosa.
Presented by the Association for Research in Vision and Ophthalmology (ARVO), the Friedenwald Award was established in 1957 as a memorial to Dr. Jonas S. Friedenwald, a distinguished researcher whose contributions encompassed the entire field of ophthalmic investigations and laid the groundwork for future generations of investigators.
[[quote-right “He is an extraordinary critical thinker who brings extensive knowledge and insight to his and his colleague’s research efforts.” “Brian Mansfield PhD”]]
“We are delighted to recognize Don for his impactful research contributions, outstanding service to the Foundation and its constituents, and receiving the prestigious Freidenwald Award,” says Brian Mansfield, PhD, executive vice president and interim chief scientific officer at the Foundation. “He is an extraordinary critical thinker who brings extensive knowledge and insight to his and his colleague’s research efforts. In addition to his innovative studies, he provides very helpful feedback and perspectives during our grants evaluation process.”
Dr. Zack received his medical degree and doctorate in molecular immunology from the Albert Einstein College of Medicine. He completed his residency in ophthalmology at the Massachusetts Eye and Ear Infirmary at Harvard University. He completed fellowship training in glaucoma and molecular biology at the Johns Hopkins University School of Medicine, and joined the faculty in 1991. Dr. Zack has published more than 160 peer-reviewed journal articles.
]]>With the convening of the new Congress in January 2019, the bill was recently re-introduced in the House as HR 2620, the Faster Treatments and Cures for Eye Diseases Act. This re-introduction was a normal part of the legislative process. Nothing about the legislation itself has changed.
The Foundation Fighting Blindness has been a driving force in gaining bipartisan support for this sight-saving legislation. There is strong momentum behind the new Eye Bonds legislation; nearly two dozen House Members co-sponsored last year’s bill.
With the new legislation, our lead original co-sponsors are Representatives Sanford Bishop, a Democrat from Georgia’s 2nd district, and Cathy McMorris Rodgers, a Republican from Washington’s 5th district. The other original co-sponsors are: Tom O’Halleran (D-AZ1), Brad Schneider (D-IL10), Steve Cohen (D-TN9), Gus Bilirakis (R-FL12), and Brian Fitzpatrick (R-PA1).
To ask the House Member in your district to support HR2620, visit Find Your Representative. Either a phone call or e-mail will work well. Let your Member know your name, where you live, and why the sight-saving legislation is important to you. You can also mention that Eye Bonds have bipartisan support and will not increase the taxpayer burden.
Eye Bonds are the vision, and many years of hard work, of Karen and Basil Petrou. Karen is a long-time Foundation board director, and she and her husband run a government financial consulting firm known as Federal Financial Analytics.
Why Eye-Bonds? Many promising therapies never make it through the translational research process — out of labs and into clinical trials — because of a lack of funding; translational research is often referred to as “crossing the Valley of Death” for this reason. Pharmaceutical companies and biotechs don’t fund translational research; they only fund projects once they have had some initial success in a clinical trial.
The bottom line: Eye Bonds provide the opportunity to advance, and accelerate development for, more promising treatments into and through clinical trials and out to the people who need them.
Eye Bonds is a pilot program. If it succeeds, the model could be used to advance translational research for other conditions and diseases.
]]>Eloxx Pharmaceuticals is a clinical-stage biopharmaceutical company dedicated to the discovery and development of novel therapeutics to treat rare diseases—including cystic fibrosis, cystinosis, and inherited retinal disorders—caused by nonsense mutations that limit production of functional proteins.
Eloxx has entered into a partnership with the Foundation Fighting Blindness and is developing molecules that “read through” nonsense mutations, a type of mutation that, in simple terms, inserts a period too early in the genetic code. Scientists call these “premature stop codons” or PSCs. Eloxx’s library of molecules is designed to enable the cell to read through these PSCs, so normal protein can be produced.
In the accompanying video, Matthew Goddeeris, PhD, Eloxx director of research, discusses how an Eloxx molecule was able to read through PSCs that lead to Usher syndrome type 1F (PCDH15) and USH2A (USH2A). While the molecule is still at an early stage of development, its potential is promising.
Scientists believe that approximately 10 percent of all the gene mutations (across all known ~270 IRD genes) are nonsense. So, read through molecules have the potential to help many people.
Dr. Goddeeris presented the Eloxx Usher research at the 2019 annual meeting of the Association for Research in Vision and Ophthalmology (ARVO) taking place in Vancouver, Canada, on April 28 - May 2, 2019.
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]]>QR-421a is an antisense oligonucleotide (AON) — a small piece of genetic material — designed to mask exon 13 mutations in the RNA of USH2A. RNA are genetic messages that cells read to make proteins critical to their health and function. QR-421a enables retinal cells to skip over exon 13 (and any mutations inside it) when reading the USH2A RNA, enabling the cells to make functional protein that will hopefully halt or slow the disease process and vision loss.
In September 2018, ProQR reported vision improvements for patients in a Phase 1 / 2 clinical trial for QR-110, an AON therapy for people with Leber congenital amaurosis 10 (LCA10) caused by the p.Cys998X mutation in the CEP290 gene. The company reported that 60 percent of subjects in the trial demonstrated improvements in visual acuity and their ability to navigate a mobility course. The treatment was also safe for patients. As a result of the encouraging interim results, ProQR concluded the Phase ½ trial and is moving the treatment into a Phase 2/3 clinical trial.
“We are excited about ProQR’s innovative AON technology for treating inherited retinal diseases,” says Brian Mansfield, PhD, executive vice president of research and interim chief scientific officer at the Foundation. “It is an elegant approach for addressing certain genetic conditions and has shown encouraging early results for LCA10.”
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