LUXTURNA Proves Effectiveness of Single Gene Therapy To Cure Rare Cause of Blindness

MedicalResearch.com Interview with:

Dr. Stephen M. Rose, PhD Chief Research Officer Foundation Fighting Blindness

Foundation Fighting Blindness

Dr. Stephen Rose PhD
Chief Research Officer
Foundation Fighting Blindness (FFB)

Dr. Rose comments on the announcement of the FDA approval of voretigene neparvovec (LUXTURNA™) gene therapy for inherited blindness due to mutations in the RPE65 gene.

What is the background for this announcement? What were the main findings from the study?

Response: While it has been 30 years since the RPE65 gene was identified as causing Leber’s Congenital Amaurosis, this shows that it is possible to have an effective gene therapy for an inherited disease. As the first gene therapy for the eye or for an inherited disease, LUXTURNA is a historic milestone in the search for cures for all inherited retinal diseases (IRDs). As a one-time gene therapy, LUXTURNA will not only be life-changing for patients with vision loss due to mutations in the RPE65 gene, it also provides critical momentum for gene therapies – for the eye and other diseases – now in the clinic.  Continue reading

Viral Vector Delivered Gene Therapy That Reversed Diabetes in Mice

MedicalResearch.com Interview with:
Xiangwei Xiao, M.D., Ph.D.
Assistant Professor of Department of Surgery,
Children’s Hospital of Pittsburgh
University of Pittsburgh School of Medicine,
Pittsburgh, PA

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

Response: Diabetes is a prevalent chronic disease characterized by persistently high blood glucose. Diabetes has two main subtypes, type 1 diabetes and type 2 diabetes. In type 1 diabetes, the immune system attacks and destroys insulin-producing beta cells in the pancreas, resulting in high blood levels of glucose. In type 2 diabetes, the beta cells do not produce enough insulin or the body is not able to use insulin effectively.

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FDA Advisory Committee Recommended Approval of First Gene Therapy For Inherited Eye Disease

MedicalResearch.com Interview with:
Dr. Stephen M. Rose, PhD Chief Research Officer Foundation Fighting BlindnessDr. Stephen M. Rose, PhD
Chief Research Officer
Foundation Fighting Blindness

Dr. Rose discusses the FDA advisory panel unanimously recommended approval of Spark Therapeutics’ Gene Therapy Luxturna  for the treatment of patients with vision loss due to confirmed biallelic RPE65-mediated inherited retinal dystrophies, a group of rare blinding conditions caused by one of more than 220 different genes.

MedicalResearch.com: Would you tell us a little about IRD? Whom does it affect and how?  How common is this disorder?

Response: The retina at the back of the eye is responsible for collecting light and turning it into signals that are transmitted to the brain and interpreted as vision. Think of the retina as the film in a camera, or more recently the sensor at the back of a digital camera. Inherited rare retinal degenerations are when the retina at the back of the eye deteriorates and loses its ability to capture light, thereby leading to blindness.

iRDs can affect anyone, no matter race or ethnicity. These are inherited conditions that are passed down from parents to children, if a parent or both parents are either affected already or are carriers for a variant in any of the over 250 genes responsible for retinal degeneration.

There are over 15 different types of iRDs, with retinitis pigmentosa being the most common with a US affected population around 100,000. The rest of the iRDs make up another approximately 100,000 affected individuals in the US, so there are about 200,000 total affected individuals in the US. Worldwide these iRDs affect somewhere around one to two million individuals.

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Single Injection of Klotho Gene Protected Animals From Cognitive Decline

MedicalResearch.com Interview with:

Dr Miguel Chillon PhD Department of Biochemistry and Molecular Biology Universitat Autonoma Barcelona Spain

Dr. Chillon

Dr Miguel Chillon PhD
Department of Biochemistry and Molecular Biology
Universitat Autonoma Barcelona
Spain

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

Response: Klotho is a protein with an anti-aging and neuroprotective role. Recent studies show it prevents the development of cognitive problems associated with aging and Alzheimer’s disease. Klotho works mainly by inhibiting the insulin / IGF-1 signaling pathway and decreasing the damage caused by oxidative stress in the brain. One of the latest results revealed that the concentration of Klotho in cerebrospinal fluid is significantly lower in Alzheimer’s patients than in human controls of the same age; and it is lower in the elderly with respect to young adults.

Our study used a gene therapy strategy to introduce the Klotho gene into the Central Nervous System of adult animals. With just a single injection of the Klotho gene, young adult animals were protected over time from the cognitive decline associated with aging in old animals. These exciting results pave the way to further advances in research and the development of a neuroprotective therapy based on Klotho.

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Novel Viral Vector Allows Gene Transfer To Correct Hearing Loss

MedicalResearch.com Interview with:

Lukas Landegger MD Molecular Neurotology Laboratory (PI Konstantina Stankovic) Massachusetts Eye and Ear Infirmary

Dr. Landegger

Lukas Landegger MD
Molecular Neurotology Laboratory (PI Konstantina Stankovic)
Massachusetts Eye and Ear Infirmary

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

Response: Genetic hearing loss affects more than 125 million people worldwide and constitutes a major hurdle for language acquisition and child development in general. Technological advances over the last decades, such as cochlear implants, have made it possible for deaf children to partially regain their sense of hearing. However, these devices still have several shortcomings, especially when listeners attempt to understand speech in noise or listen to music.

In establishing Anc80L65 as a reliable vector for gene delivery in the inner ear and releasing the first data demonstrating convincing hearing and vestibular function rescue in mice, we provide a foundation for other researchers interested in assessing the benefits of gene therapy in animal models of human disease.

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Gene Therapy Restores Hearing Down To A Whisper, in Mice

MedicalResearch.com Interview with:

Gwenaelle Geleoc, PhD Assistant Professor Department of Otolaryngology F.M. Kirby Neurobiology Center Children's Hospital and Harvard Medical School Boston, MA

Dr. Gwenaelle Geleoc

Gwenaelle Geleoc, PhD
Assistant Professor
Department of Otolaryngology
F.M. Kirby Neurobiology Center
Children’s Hospital and Harvard Medical School
Boston, MA

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

Response: We seek to develop gene therapy to restore auditory and balance function in a mouse model of Usher syndrome. Usher syndrome is a rare genetic disorder which causes deafness, progressive blindness and in some cases balance deficits. We used a novel viral vector developed by Luk Vandenberghe and package gene sequences encoding for Ush1c and applied it to young mice suffering from Usher syndrome. These mice mimic a mutation found in patients of Acadian descent. We assessed recovery of hearing and balance function in young adult mice which had received the treatment. Otherwise deaf and dizzy, we found that the treated mice had recovered hearing down to soft sounds equivalent to a whisper and normal balance function.

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Early Use of Gene Therapy May Stop Plaques of Alzheimer’s Disease

MedicalResearch.com Interview with:

Dr. Magdalena Sastre PhD Faculty of Medicine, Department of Medicine Senior Lecturer Imperial College London

Dr. Magdalena Sastre

Dr. Magdalena Sastre PhD
Faculty of Medicine, Department of Medicine
Senior Lecturer
Imperial College London

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

Response: Alzheimer’s disease is the most common neurodegenerative disorder, affecting over 45 million people around the world. Currently, there are no therapies to cure or stop the progression of the disease. Here, we have developed a gene therapy approach whereby we delivered a factor called PGC-1α, which regulates the expression of genes involved in metabolism, inflammation and oxidative stress in the brain of transgenic mice. This factor is also involved in the regulation of energy in the cells, because it controls the genesis of mitochondria and in the generation of amyloid-β, the main component of the neuritic plaques present in the brains of Alzheimer’s disease patients.

We have found that the animals with Alzheimer’s pathology treated with PGC-1α develop less amyloid plaques in the brain, perform memory tasks as well as healthy mice and do not have neuronal loss in the brain areas affected by the disease.

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Gene Therapy Delivers Intracellular Antibodies To Attack Abnormal Protein in Huntington’s Disease

MedicalResearch.com Interview with:
Lee Henderson, Ph.D. CEO Vybion, Inc. Ithaca, NY 14852Lee Henderson, Ph.D.
CEO, Vybion, Inc.
Ithaca, NY 14852

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

Response: Huntington’s disease (HD) is a progressive and fatal neurodegenerative disease characterized by loss of both cognitive and motor function as a result of neuron loss primarily within the brain striatum. HD is directly caused by the expansion of CAG repeats in the huntingtin gene resulting in an expanded glutamine region (polyQ) near the N-terminus of the protein. Age of disease onset and the rate of progression is directly correlated to the size of the expansion with pathology observable at 35-70 repeats in adults and greater in juvenile onset. During normal turnover and degradation of the huntingtin protein, the N-terminal polyQ-containing fragments drive pathology and aggregate formation in cells. The direct link to progression has been described by several laboratories using cell-based and animal model studies and confirmed in humans as the binding of these N-terminal fragments to DNA and transcription factors that result in widespread gene dysregulation in neurons.

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Gene Therapy to Spinal Cord Offers Potential Hope to Peripheral Nerve Pain Patients

MedicalResearch.com Interview with:

Hui-Lin Pan, MD, PhD Helen T. Hawkins Distinguished Professor  and Deputy Division Head for Research Division of Anesthesiology and Critical Care, Unit 110 The University of Texas MD Anderson Cancer Center Houston, TX

Dr. Hui-Lin Pan

Hui-Lin Pan, MD, PhD
Helen T. Hawkins Distinguished Professor
and Deputy Division Head for Research
Division of Anesthesiology and Critical Care, Unit 110
The University of Texas MD Anderson Cancer Center
Houston, TX

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

Dr. Hui-Lin Pan: Chronic nerve pain caused by damage to the peripheral nerve is a debilitating health problem and remains very difficult to treat. Sensory neurons in the spinal cord are normally inhibited by inhibitory neurotransmitters (GABA and glycine) to regulate transmission of painful information. A major feature of nerve injury-induced chronic pain is reduced spinal cord inhibition, resulting from diminished activity of a chloride transporter called KCC2. In this study, we investigated whether increasing KCC2 expression at the spinal level using a lentiviral vector can restore KCC2 activity, thereby reducing chronic nerve pain.

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CRISPR Editing May Lead To Genetic Treatment of Retinitis Pigmentosa

More on Gene Therapy on MedicalResearch.com

Benjamin Bakondi, Ph.D. Postdoctoral Scientist, Eye Program Board of Governors Regenerative Medicine Institute Cedars-Sinai Medical Center; Dept. of Biomedical Sciences Los Angeles, CA 90048

Dr. Benjamin Bakondi

MedicalResearch.com Interview with:
Benjamin Bakondi, Ph.D. Postdoctoral Scientist
Laboratory of: Shaomei Wang, M.D., Ph.D.
Institute Director: Clive N. Svendsen, Ph.D.
Board of Governors Regenerative Medicine Institute
Cedars-Sinai Medical Center;
Dept. of Biomedical Sciences
Los Angeles, CA 90048

Medical Research: What is the background for this study? What are the main findings?

Dr. Bakondi: Retinitis Pigmentosa (RP) is an inherited disease that causes progressive retinal degeneration and continual vision loss. Over 130 mutations have been identified in over 60 genes that cause RP. Gene replacement therapy is being evaluated for the recessive form of RP, in which both inherited alleles are dysfunctional. Retinitis Pigmentosa arising from dominant mutations however, would not benefit from such a strategy, and alternative options have not demonstrated clear efficacy.

The idea for a therapeutic based on our approach is to use CRISPR/Cas9 to ablate the mutant copy of an allele and leave the wild-type copy unaffected. Barring haploinsufficiency, the wild-type allele should restore function and prevent retinal degeneration at levels commensurate with Cas9 cleavage efficiency. Our experimental findings provide proof-of-principle that a single DNA nucleotide difference in the genomic sequence between mutant and wild-type genes is enough to distinguish the mutant transcript for Cas9 cleavage with high fidelity. Eliminating production of the mutant rhodopsin protein prevented retinal degeneration and preserved vision. While Cas9/gRNA delivery improvement is underway, it should be noted that translational applicability of this approach is restricted to dominant mutations, not all of which may be targetable for ablation therapy.

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