One Time Injection With Spark’s Gene Therapy LUXTURNA Demonstrated Lasting Visual Improvement

MedicalResearch.com Interview with:

Stephen R. Russell, MD Dina J Schrage Professor of Macular Degeneration Research Service Director, Vitreoretinal Diseases and Surgery Professor of Ophthalmology and Visual Sciences The University of Iowa

Dr. Russell

Stephen R. Russell, MD
Dina J Schrage Professor of Macular Degeneration Research
Service Director, Vitreoretinal Diseases and Surgery
Professor of Ophthalmology and Visual Sciences
The University of Iowa

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: This study examines the efficacy (and safety) of treating children and adults with a form of retinitis pigmentosa known as RPE65-associated Lebers congenital amaurosis, with an adeno-associated viral vector(AAV) delivered RPE65 construct.  Building on successful phase 1/2b trials from multiple centers, the AAV-hRPE65v2 agent now designated as voretigene neparvovec, contains a highly optimized enhancing sequence and promoter.

The main findings were an improvement on a multiple light level mobility test (MLMT) and multiple additional supportive secondary endpoints which included improvements in full-field light sensitivity, Goldmann visual field, and others.

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Eyedrop Kallikrein Inhibitor Shows Promise for Diabetic Macular Edema

MedicalResearch.com Interview with:
Dr. David Kita, PhD Founder and Head of R&D Verseon CorporationDr. David Kita, PhD
Founder and Head of R&D
Verseon Corporation

MedicalResearch.com: What is the background for this study?

Dr. Kita: The preclinical data presented at the 2017 BIO International Conference provided details about Verseon’s plasma kallikrein inhibitors for the treatment of diabetic macular edema (DME).

DME affects millions of people worldwide and is a major cause of vision loss in patients with diabetes mellitus. Upregulation of the kallikrein-kinin system in response to diabetes can result in retinal vascular permeability, which can damage the retina and eventually lead to the central vision loss associated with DME.

The current treatment options for DME include intravitreal injections of anti-VEGF agents or corticosteroids into the eye and surgical laser treatments. Long-term use of intravitreal injections is associated with side effects such as inflammation, infections, and cataracts. For anti-VEGF drugs in particular, there is also a growing concern about geographic atrophy. In addition, about 50% of patients reported at most moderate vision improvements following anti-VEGF therapy in clinical trials. This highlights the need for a new treatment that can serve as a monotherapy or as an adjuvant to current therapies.

At Verseon, we are working on inhibitors of the serine protease plasma kallikrein (KLKB1) that can be administered either topically or orally. Verseon’s unique computer-driven drug discovery platform allows us to design potent, selective drug candidates that are unlikely to be found using traditional approaches. We have generated a number of chemically distinct series of KLKB1 inhibitors and optimized multiple lead candidates, which show good activity, permeability, and solubility.

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Phase I Study Shows IV Gene Therapy May Improve Macular Degeneration

MedicalResearch.com Interview with:

Prof Peter A Campochiaro MD Director, Retinal Cell and Molecular Laboratory Professor of Ophthalmology Johns Hopkins University School of Medicine Baltimore, MD

Dr. Campochiaro

Prof Peter A Campochiaro MD
Director, Retinal Cell and Molecular Laboratory
Professor of Ophthalmology
Johns Hopkins University School of Medicine
Baltimore, MD

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Patients with wet age-related macular degeneration (AMD) have increased levels of vascular endothelial growth factor (VEGF) in their eyes resulting in growth of abnormal blood vessels that leak fluid into the retina and reduce vision. The current treatment is to inject proteins that block VEGF which initially provides a very good effect, but repeated injections are needed.

Patients sometimes are unable to keep up the frequency of visits and injections needed to keep the disease quiet and over time there is often gradual loss of vision. The aim of this study was to test a new approach through which a viral vector is injected into the eye resulting in production of a protein that block VEGF in the eye reducing the need for repeated injections.

These are the major findings:

1) Intravitreous injection of an AAV2 vector expressing a protein that blocks vascular endothelial growth factor (VEGF) was safe and well-tolerated.

(2) 5 of 10 patients injected with the highest dose (2 × 10¹⁰ vector genomes) had measurable levels of the therapeutic protein in samples removed from the front of the eye- all of these patients had no or very low levels of anti-AAV2 serum antibodies and 4 of the 5 patients who did not show expression had high anti-AAV2 serum antibodies

(3) Eleven patients had fluid in or under the retina before vector injection and 6 of them showed substantial reduction of the fluid which is the desired outcome.

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New Technology May Allow Topical Delivery of Anti-VEGF Drugs For Macular Degeneration

MedicalResearch.com Interview with:

Dr Felicity de Cogan PhD</strong> Institute of Inflammation and Ageing University of Birmingham

Dr Felicity de Cogan

Dr Felicity de Cogan PhD
Institute of Inflammation and Ageing
University of Birmingham

MedicalResearch.com: What is the background for this study?

Response: The University of Birmingham has a unique approach to developing technologies. By locating chemists, engineers, biologists and clinicians in the same department it revolutionised the way research problems are solved.

Initially, Felicity de Cogan was researching cell penetrating peptides (CPP) and their uses in microbiology. However, after joining forces with Neuroscientists, Dr Lisa Hill and Professor Ann Logan at the National Institute for Health Research Surgical Reconstruction and Microbiology Research Centre (NIHR SRMRC) together with the clinicians and Vision Scientists, Dr Mei Chen and Professor Heping Xu at the Queen’s University Belfast it became evident that there was huge potential to deliver drugs in the eye. This was the start of the project and it developed rapidly from there.

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Gene Delivered By Nanoparticle System Can Potentially Cure Congenital Blindness

MedicalResearch.com Interview with:
Zheng-Rong Lu, Ph.D.

M. Frank Rudy and Margaret Domiter Rudy Professor of Biomedical Engineering
Department of Biomedical Engineering
Case Western Reserve University
Cleveland, OH 44106

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Genetic vision disorders are a major cause of severe vision loss and blindness, especially in children and young adults. Currently, there are no approved therapies to treat these types of disorders.

This study focused on one such disease known as Leber’s congenital amaurosis type 2 (LCA2). Patients with LCA2 are born with some degree of vision loss, and are often legally blind by early adulthood. LCA2 is a recessive disease caused by a mutation in one of the genes responsible for visual processing. LCA2 is a good candidate for gene therapy, and clinical trials underway to test viral vectors that deliver a healthy copy of the mutated gene into the eye have demonstrated considerable therapeutic efficacy. These trials have validated the feasibility of gene therapy to treat this disease, however viral vectors are limited by potential safety issues, complex preparation methods, and limitations on the size of genes that can be delivered.

In this study, we successfully treated LCA2 in mice for 120 days by delivering the gene responsible for LCA2 in a synthetic lipid nanoparticle instead of a viral vector. Our delivery system, called ECO, specifically targets the cells in the retinal pigmented epithelium, where the mutation behind LCA2 occurs. Our nanoparticle delivery system is easy to produce, safe, and has unlimited cargo capacity. Most important, our nanoparticle gene delivery system is a platform that can be used to deliver any gene into the retina, opening the door for safe and effective gene therapy for any genetic vision disorder.

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Study Compares Systemic Therapy vs Ocular Implant For Uveitis

MedicalResearch.com Interview with:

John H Kempen, MD, PhD Protocol Chair, MUST Trial Follow-up Study; Vice Chair, MUST Research Group Director of Epidemiology for Ophthalmology, Massachusetts Eye and Ear Harvard Medical School Editor-in-Chief, Ophthalmic Epidemiology President, Sight for Souls

Dr. Kempen

John H Kempen, MD, PhD
Protocol Chair, MUST Trial Follow-up Study; Vice Chair, MUST Research Group
Director of Epidemiology for Ophthalmology, Massachusetts Eye and Ear
Harvard Medical School
Editor-in-Chief, Ophthalmic Epidemiology
President, Sight for Souls

MedicalResearch.com: What is the background for this study?

Response: Uveitis is about the fifth leading cause of blindness in the united states.  Among types of uveitis, intermediate, posterior and panuveitis are the leading causes of blindness.  Before 2005, systemic therapy with corticosteroids—supplemented when indicated with immunosuppressive drugs (most of the time)—was the primary treatment recommended for these conditions.  With approval of the fluocinolone acetonide implant in 2005 for intermediate, posterior and panuveitis, it became unclear which of the alternative treatment approaches should be the treatment of choice.

The multicenter uveitis steroid treatment (must) trial was initiated in 2005 to directly compare the alternative treatments.  Systemic therapy was administered using high dose prednisone followed by tapering of corticosteroids to maintenance doses of 10 mg/day or less (generally 7.5 mg/day or less) or to zero; this was supplemented by immunosuppressive corticosteroid-sparing drugs in 88% of participants.  Implant therapy was done by initial quieting of the anterior chamber of the eye with topical, injected or systemic corticosteroids followed by surgical implant placement within 28 days (first eye) and 56 days (second eye if it was indicated).  After this, systemic corticosteroids and immunosuppressive drugs were tapered off.

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Number of Preschool Children With Visual Impairment Projected To Rise

MedicalResearch.com Interview with:

Rohit Varma, MD, MPH</strong> Executive Director - USC Roski Eye Institute and Dean of the Keck School of Medicine of USC

Dr. Varma

Rohit Varma, MD, MPH
Executive Director – USC Roski Eye Institute and
Dean of the Keck School of Medicine of USC

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Visual impairment in early childhood has profound impact on a child’s development. It can significantly impair development of visual, motor, and cognitive function1-3 and lead to adverse psychosocial consequences. There has been a lack of accurate data characterizing the current and expected numbers of visual impairment cases among preschool children in the United States from 2015 to 2060.

The number of preschool children with visual impairment is projected to increase by 26% in 2060. And 69% of these visual impairment will result from simple uncorrected refractive error such hyperopia and myopia, which can be prevented or treated by low-cost refractive correction.

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Age-related Macular Degeneration Underdiagnosed in Primary Care

MedicalResearch.com Interview with:

David C Neely, MD The University of Alabama at Birmingham

Dr. Neely

David C Neely, MD
The University of Alabama at Birmingham

MedicalResearch.com: What is the background for this study? What are the main
findings?

Response: This study examined the prevalence of eyes with age-related macular degeneration (AMD) in patients seen in primary eye care clinics who purportedly have normal macular health.

Approximately 25.0% of eyes deemed to be normal based on dilated eye examination by primary eye care providers had macular characteristics that indicated age-related macular degeneration. Continue reading

CRISPR Gene Editing May Lead To Cure For Retinitis Pigmentosa

MedicalResearch.com Interview with:

Kang Zhang, M.D., Ph.D.</strong> Professor of Ophthalmology Chief, Ophthalmic Genetics Founding Director, Institute for Genomic Medicine Co-Director, Biomaterials and Tissue Engineering, Institute for Engineering in Medicine Board Certification in Ophthalmology Fellowship in Vitreoretinal Disease and Surgery Guangzhou Women and Children's Medical Center Guangzhou Medical University Guangzhou China

Dr. Kang Zhang

Kang Zhang, M.D., Ph.D.
Professor of Ophthalmology
Chief, Ophthalmic Genetics
Founding Director, Institute for Genomic Medicine
Co-Director, Biomaterials and Tissue Engineering, Institute for Engineering in Medicine
Board Certification in Ophthalmology
Fellowship in Vitreoretinal Disease and Surgery
Guangzhou Women and Children’s Medical Center
Guangzhou Medical University
Guangzhou China
MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Retinitis pigmentosa is a common blinding condition characterized by mutations in rod photoreceptor specific genes, night blindness and tunnel visual with eventual loss of day vision. Since it can be caused by numerous different mutations in many genes therefore it has been difficult to provide treatment benefits to a majority of patients. Traditional gene therapy has been in a piece-meal fashion, meaning to create a therapy for a particular gene or mutation. In this paper, we describe a universal gene therapy approach using the latest gene editing technology CRISPR/CAS9 to reprogram rod photoreceptors to cone photoreceptors with reversal of RP and restoration of vision.

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Outbreak of Severe Fungal Eye Infections Linked To IV Opioid Epidemic

MedicalResearch.com Interview with:
Aubrey Tirpack, PGY3

New England Eye Center
Tufts Medical Center 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Intravenous drug abuse is a known risk factor for the development of endogenous fungal endophthalmitis (EFE), a severe intraocular infection cause by the seeding of mycotic organisms to the eye.

Our institution noted a marked increase in cases of EFE beginning in May 2014, which correlates to increasing rates of opioid abuse throughout the New England region. Ten patients were found to have intravenous drug abuse related EFE over the two year time period studied. The most common presenting symptoms were floaters, decreased vision, and pain. All patients were treated with systemic antifungals and nine patients underwent intravitreal antifungal injection. All patients were ambulatory at presentation and the majority were without systemic signs of infection.

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