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2. Outcomes of hematopoietic stem cell gene therapy for Wiskott-Aldrich syndrome

Author

Labrosse, Roxane, Chu, Julia I., Armant, Myriam A., Everett, John K., Pellin, Danilo, Kareddy, Niharika, Frelinger, Andrew L., Henderson, Lauren A., O’Connell, Amy E., Biswas, Amlan, Coenen-van der Spek, Jet, Miggelbrink, Alexandra, Fiorini, Claudia, Adhikari, Hriju, Berry, Charles C., Cantu, Vito Adrian, Fong, Johnson, Jaroslavsky, Jason, Karadeniz, Derin F., Li, Quan-Zhen, Reddy, Shantan, Roche, Aoife M., Zhu, Chengsong, Whangbo, Jennifer S., Dansereau, Colleen, Mackinnon, Brenda, Morris, Emily, Koo, Stephanie M., London, Wendy B., Baris, Safa, Ozen, Ahmet, Karakoc-Aydiner, Elif, Despotovic, Jenny M., Forbes Satter, Lisa R., Saitoh, Akihiko, Aizawa, Yuta, King, Alejandra, Nguyen, Mai Anh Thi, Vu, Vy Do Uyen, Snapper, Scott B., Galy, Anne, Notarangelo, Luigi D., Bushman, Frederic D., Williams, David A., and Pai, Sung-Yun

Published
2023
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3. Rapid manufacturing of non-activated potent CAR T cells

Author

Ghassemi, Saba, Durgin, Joseph S., Nunez-Cruz, Selene, Patel, Jai, Leferovich, John, Pinzone, Marilia, Shen, Feng, Cummins, Katherine D., Plesa, Gabriela, Cantu, Vito Adrian, Reddy, Shantan, Bushman, Frederic D., Gill, Saar I., O’Doherty, Una, O’Connor, Roddy S., and Milone, Michael C.

Published
2022
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4. Lentiviral globin gene therapy with reduced-intensity conditioning in adults with β-thalassemia: a phase 1 trial

Author

Boulad, Farid, Maggio, Aurelio, Wang, Xiuyan, Moi, Paolo, Acuto, Santina, Kogel, Friederike, Takpradit, Chayamon, Prockop, Susan, Mansilla-Soto, Jorge, Cabriolu, Annalisa, Odak, Ashlesha, Qu, Jinrong, Thummar, Keyur, Du, Fang, Shen, Lingbo, Raso, Simona, Barone, Rita, Di Maggio, Rosario, Pitrolo, Lorella, Giambona, Antonino, Mingoia, Maura, Everett, John K., Hokama, Pascha, Roche, Aoife M., Cantu, Vito Adrian, Adhikari, Hriju, Reddy, Shantan, Bouhassira, Eric, Mohandas, Narla, Bushman, Frederic D., Rivière, Isabelle, and Sadelain, Michel

Published
2022
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5. Long-term outcomes after gene therapy for adenosine deaminase severe combined immune deficiency

Author

Reinhardt, Bryanna, Habib, Omar, Shaw, Kit L., Garabedian, Elizabeth, Carbonaro-Sarracino, Denise A., Terrazas, Dayna, Fernandez, Beatriz Campo, De Oliveira, Satiro, Moore, Theodore B., Ikeda, Alan K., Engel, Barbara C., Podsakoff, Gregory M., Hollis, Roger P., Fernandes, Augustine, Jackson, Connie, Shupien, Sally, Mishra, Suparna, Davila, Alejandra, Mottahedeh, Jack, Vitomirov, Andrej, Meng, Wenzhao, Rosenfeld, Aaron M., Roche, Aoife M., Hokama, Pascha, Reddy, Shantan, Everett, John, Wang, Xiaoyan, Luning Prak, Eline T., Cornetta, Kenneth, Hershfield, Michael S., Sokolic, Robert, De Ravin, Suk See, Malech, Harry L., Bushman, Frederic D., Candotti, Fabio, and Kohn, Donald B.

Published
2021
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6. INSPIIRED: A Pipeline for Quantitative Analysis of Sites of New DNA Integration in Cellular Genomes

Author

Sherman, Eric, Nobles, Christopher, Berry, Charles C, Six, Emmanuelle, Wu, Yinghua, Dryga, Anatoly, Malani, Nirav, Male, Frances, Reddy, Shantan, Bailey, Aubrey, Bittinger, Kyle, Everett, John K, Caccavelli, Laure, Drake, Mary J, Bates, Paul, Hacein-Bey-Abina, Salima, Cavazzana, Marina, and Bushman, Frederic D

Subjects
Human Genome, Networking and Information Technology R&D (NITRD), Bioengineering, Genetics, Biotechnology, Generic health relevance, SCID-X1, gammaretrovirus, gene therapy, insertional mutagenesis, lentivirus, mutagenesis, recombination, retrovirus, vector, vector driving
Abstract

Integration of new DNA into cellular genomes mediates replication of retroviruses and transposons; integration reactions have also been adapted for use in human gene therapy. Tracking the distributions of integration sites is important to characterize populations of transduced cells and to monitor potential outgrow of pathogenic cell clones. Here, we describe a pipeline for quantitative analysis of integration site distributions named INSPIIRED (integration site pipeline for paired-end reads). We describe optimized biochemical steps for site isolation using Illumina paired-end sequencing, including new technology for suppressing recovery of unwanted contaminants, then software for alignment, quality control, and management of integration site sequences. During library preparation, DNAs are broken by sonication, so that after ligation-mediated PCR the number of ligation junction sites can be used to infer abundance of gene-modified cells. We generated integration sites of known positions in silico, and we describe optimization of sample processing parameters refined by comparison to truth. We also present a novel graph-theory-based method for quantifying integration sites in repeated sequences, and we characterize the consequences using synthetic and experimental data. In an accompanying paper, we describe an additional set of statistical tools for data analysis and visualization. Software is available at https://github.com/BushmanLab/INSPIIRED.

Published
2017

7. CD19-targeting CAR T cell immunotherapy outcomes correlate with genomic modification by vector integration

Author

Nobles, Christopher L., Sherrill-Mix, Scott, Everett, John K., Reddy, Shantan, Fraietta, Joseph A., Porter, David L., Frey, Noelle, Gill, Saar I., Grupp, Stephan A., Maude, Shannon L., Siegel, Donald L., Levine, Bruce L., June, Carl H., Lacey, Simon F., Melenhorst, J. Joseph, and Bushman, Frederic D.

Subjects
Genes, Chromatin, Immunotherapy, Genomes, Genomics, T cells, Lymphocytic leukemia, Antigens, Chronic lymphocytic leukemia, Acute lymphocytic leukemia, Pediatrics, Health care industry
Abstract

Chimeric antigen receptor-engineered T cells targeting CD19 (CART19) provide an effective treatment for pediatric acute lymphoblastic leukemia but are less effective for chronic lymphocytic leukemia (CLL), focusing attention on improving efficacy. CART19 harbor an engineered receptor, which is delivered through lentiviral vector integration, thereby marking cell lineages and modifying the cellular genome by insertional mutagenesis. We recently reported that vector integration within the host TET2 gene was associated with CLL remission. Here, we investigated clonal population structure and therapeutic outcomes in another 39 patients by high-throughput sequencing of vector-integration sites. Genes at integration sites enriched in responders were commonly found in cell-signaling and chromatin modification pathways, suggesting that insertional mutagenesis in these genes promoted therapeutic T cell proliferation. We also developed a multivariate model based on integration-site distributions and found that data from preinfusion products forecasted response in CLL successfully in discovery and validation cohorts and, in day 28 samples, reported responders to CLL therapy with high accuracy. These data clarify how insertional mutagenesis can modulate cell proliferation in CART19 therapy and how data on integration- site distributions can be linked to treatment outcomes., Introduction Patient T cells engineered to express a CD19-specific chimeric antigen receptor (CART19) have proven effective in inducing long-term remissions in pediatric acute lymphoblastic leukemia (ALL), with complete response rates [...]

Published
2020
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8. Novel KRIT1/CCM1 mutation in a patient with retinal cavernous hemangioma and cerebral cavernous malformation

Author

Reddy, Shantan, Gorin, Michael B., McCannel, Tara A., Tsui, Irena, and Straatsma, Bradley R.

Subjects
Medicine & Public Health, Ophthalmology, Cerebral cavernous malformation, KRIT1, Mutation, Retinal cavernous hemangioma
Abstract

Retinal cavernous hemangiomas are rare vascular anomalies, and can be associated with cerebral cavernous malformations (CCM). Distinct mutations have been reported in patients who have both CCMs and retinal cavernous hemangiomas.Fluorescein angiography, spectral domain optical coherence tomography, and genetic testing were performed on a patient with a retinal cavernous hemangioma and a CCM.Our patient was heterozygous in the KRIT1/CCM1 gene for a frameshift mutation, c.1088delC. This would be predicted to result in premature protein termination.We have identified a novel mutation in the KRIT1/CCM1 gene in a patient with both CCM and retinal cavernous hemangioma. We hypothesize that the occurrence of retinal cavernous hemangiomas and CCMs is underlaid by a common mechanism present in the KRIT1/CCM1 gene.

Published
2010

9. Age-related macular degeneration: experimental and emerging treatments

Author

Hubschman, Jean Pierre, Reddy, Shantan, and Schwartz, Steven D

Subjects
Eye Disease and Disorders of Vision, Neurodegenerative, Aging, Macular Degeneration, Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, Eye, age-related macular degeneration, VEGF, SiRNA, PEDF, Opthalmology and Optometry
Abstract

PurposeThis essay reviews the experimental treatments and new imaging modalities that are currently being explored by investigators to help treat patients with age-related macular degeneration (AMD).DesignInterpretative essay.MethodsLiterature review and interpretation.ResultsExperimental treatments to preserve vision in patients with exudative AMD include blocking vascular endothelial growth factor (VEGF), binding VEGF, and modulating the VEGF receptors. Investigators are also attempting to block signal transduction with receptor tyrosine kinase inhibitors. Experimental treatments for non-exudative AMD include agents that target inflammation, oxidative stress, and implement immune-modulation. The effectiveness of these newer pharmacologic agents has the potential to grow exponentially when used in combination with new and improved imaging modalities that can help identify disease earlier and follow treatment response more precisely.ConclusionWith a better understanding, at the genetic and molecular level, of AMD and the development of superior imaging modalities, investigators are able to offer treatment options that may offer unprecedented visual gains while reducing the need for repetitive treatments.

Published
2009

10. Age-related macular degeneration: current treatments

Author

Hubschman, Jean Pierre, Reddy, Shantan, and Schwartz, Steven D

Subjects
Eye Disease and Disorders of Vision, Macular Degeneration, Neurodegenerative, Aging, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Eye, age-related macular degeneration, VEGF, photodynamic therapy, laser, surgery, Opthalmology and Optometry
Abstract

PurposeAlthough important progress has been made in understanding age-related macular degeneration (AMD), management of the disease continues to be a challenge. AMD research has led to a widening of available treatment options and improved prognostic perspectives. This essay reviews these treatment options.DesignInterpretative essay.MethodsLiterature review and interpretation.ResultsCurrent treatments to preserve vision in patients with non-exudative AMD include antioxidant vitamins and mineral supplementations. Exudative AMD is currently most often treated monthly with anti-VEGF intravitreal injections. However, investigators are beginning to experiment with combination therapy and surgical approaches in an attempt to limit the number of treatment and reduce the financial burden on the health care system.ConclusionBy better understanding the basis and pathogenesis of AMD, newer therapies will continue to be developed that target specific pathways in patients with AMD, with the hoped for outcome of better management of the disease and improved visual acuity.

Published
2009

12. Disruption of TET2 promotes the therapeutic efficacy of CD19-targeted T cells

Author

Fraietta, Joseph A., Nobles, Christopher L., Sammons, Morgan A., Lundh, Stefan, Carty, Shannon A., Reich, Tyler J., Cogdill, Alexandria P., Morrissette, Jennifer J. D., DeNizio, Jamie E., Reddy, Shantan, Hwang, Young, Gohil, Mercy, Kulikovskaya, Irina, Nazimuddin, Farzana, Gupta, Minnal, Chen, Fang, Everett, John K., Alexander, Katherine A., Lin-Shiao, Enrique, Gee, Marvin H., Liu, Xiaojun, Young, Regina M., Ambrose, David, Wang, Yan, Xu, Jun, Jordan, Martha S., Marcucci, Katherine T., Levine, Bruce L., Garcia, K. Christopher, Zhao, Yangbing, Kalos, Michael, Porter, David L., Kohli, Rahul M., Lacey, Simon F., Berger, Shelley L., Bushman, Frederic D., June, Carl H., and Melenhorst, J. Joseph

Published
2018
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14. Multiple Introductions of SARS-CoV-2 Alpha and Delta Variants into White-Tailed Deer in Pennsylvania

Author

Marques, Andrew D., primary, Sherrill-Mix, Scott, additional, Everett, John K., additional, Adhikari, Hriju, additional, Reddy, Shantan, additional, Ellis, Julie C., additional, Zeliff, Haley, additional, Greening, Sabrina S., additional, Cannuscio, Carolyn C., additional, Strelau, Katherine M., additional, Collman, Ronald G., additional, Kelly, Brendan J., additional, Rodino, Kyle G., additional, Bushman, Frederic D., additional, Gagne, Roderick B., additional, and Anis, Eman, additional

Published
2022
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15. Correction for Merenstein et al., “Signatures of COVID-19 Severity and Immune Response in the Respiratory Tract Microbiome”

Author

Merenstein, Carter, primary, Liang, Guanxiang, additional, Whiteside, Samantha A., additional, Cobián-Güemes, Ana G., additional, Merlino, Madeline S., additional, Taylor, Louis J., additional, Glascock, Abigail, additional, Bittinger, Kyle, additional, Tanes, Ceylan, additional, Graham-Wooten, Jevon, additional, Khatib, Layla A., additional, Fitzgerald, Ayannah S., additional, Reddy, Shantan, additional, Baxter, Amy E., additional, Giles, Josephine R., additional, Oldridge, Derek A., additional, Meyer, Nuala J., additional, Wherry, E. John, additional, McGinniss, John E., additional, Bushman, Frederic D., additional, and Collman, Ronald G., additional

Published
2022
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16. SARS-CoV-2 Variants Associated with Vaccine Breakthrough in the Delaware Valley through Summer 2021

Author

Marques, Andrew D., primary, Sherrill-Mix, Scott, additional, Everett, John K., additional, Reddy, Shantan, additional, Hokama, Pascha, additional, Roche, Aoife M., additional, Hwang, Young, additional, Glascock, Abigail, additional, Whiteside, Samantha A., additional, Graham-Wooten, Jevon, additional, Khatib, Layla A., additional, Fitzgerald, Ayannah S., additional, Moustafa, Ahmed M., additional, Bianco, Colleen, additional, Rajagopal, Swetha, additional, Helton, Jenna, additional, Deming, Regan, additional, Denu, Lidiya, additional, Ahmed, Azad, additional, Kitt, Eimear, additional, Coffin, Susan E., additional, Newbern, Claire, additional, Mell, Josh Chang, additional, Planet, Paul J., additional, Badjatia, Nitika, additional, Richards, Bonnie, additional, Wang, Zi-Xuan, additional, Cannuscio, Carolyn C., additional, Strelau, Katherine M., additional, Jaskowiak-Barr, Anne, additional, Cressman, Leigh, additional, Loughrey, Sean, additional, Ganguly, Arupa, additional, Feldman, Michael D., additional, Collman, Ronald G., additional, Rodino, Kyle G., additional, Kelly, Brendan J., additional, and Bushman, Frederic D., additional

Published
2022
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18. SARS-CoV-2 variants associated with vaccine breakthrough in the Delaware Valley through summer 2021

Author

Marques, Andrew, primary, Sherrill-Mix, Scott, additional, Everett, John K, additional, Reddy, Shantan, additional, Hokama, Pascha, additional, Roche, Aoife M, additional, Hwang, Young, additional, Glascock, Abigail, additional, Whiteside, Samantha A, additional, Graham-Wooten, Jevon, additional, Khatib, Layla A, additional, Fitzgerald, Ayannah S, additional, Moustafa, Ahmed, additional, Bianco, Colleen, additional, Rajagopal, Swetha, additional, Helton, Jenna, additional, Deming, Regan, additional, Denu, Lidiya, additional, Azad, Ahmed, additional, Kitt, Eimear, additional, Coffin, Susan, additional, Newbern, Claire, additional, Mell, Josh C, additional, Planet, Paul J, additional, Badjatia, Nitika, additional, Wang, Zi-Xuan, additional, Cannuscio, Carolyn C, additional, Strelau, Katherine, additional, Jaskowiak-Barr, Anne, additional, Cressman, Leigh, additional, Loughrey, Sean, additional, Ganguly, Arupa, additional, Feldman, Michael D, additional, Collman, Ronald G, additional, Rodino, Kyle G, additional, Kelly, Brendan J, additional, and Bushman, Frederic D, additional

Published
2021
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19. Signatures of COVID-19 Severity and Immune Response in the Respiratory Tract Microbiome

Author

Merenstein, Carter, primary, Liang, Guanxiang, additional, Whiteside, Samantha A., additional, Cobián-Güemes, Ana G., additional, Merlino, Madeline S., additional, Taylor, Louis J., additional, Glascock, Abigail, additional, Bittinger, Kyle, additional, Tanes, Ceylan, additional, Graham-Wooten, Jevon, additional, Khatib, Layla A., additional, Fitzgerald, Ayannah S., additional, Reddy, Shantan, additional, Baxter, Amy E., additional, Giles, Josephine R., additional, Oldridge, Derek A., additional, Meyer, Nuala J., additional, Wherry, E. John, additional, McGinniss, John E., additional, Bushman, Frederic D., additional, and Collman, Ronald G., additional

Published
2021
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21. Comparative Analysis of Emerging B.1.1.7+E484K SARS-CoV-2 Isolates

Author

Moustafa, Ahmed M, primary, Bianco, Colleen, additional, Denu, Lidiya, additional, Ahmed, Azad, additional, Coffin, Susan E, additional, Neide, Brandy, additional, Everett, John, additional, Reddy, Shantan, additional, Rabut, Emilie, additional, Deseignora, Jasmine, additional, Feldman, Michael D, additional, Rodino, Kyle G, additional, Bushman, Frederic, additional, Harris, Rebecca M, additional, Chang Mell, Josh, additional, and Planet, Paul J, additional

Published
2021
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22. Comparative Analysis of Emerging B.1.1.7+E484K SARS-CoV-2 isolates from Pennsylvania

Author

Moustafa, Ahmed M., primary, Bianco, Colleen, additional, Denu, Lidiya, additional, Ahmed, Azad, additional, Neide, Brandy, additional, Everett, John, additional, Reddy, Shantan, additional, Rabut, Emilie, additional, Deseignora, Jasmine, additional, Feldman, Michael D., additional, Rodino, Kyle G., additional, Bushman, Frederic, additional, Harris, Rebecca M., additional, Mell, Josh Chang, additional, and Planet, Paul J., additional

Published
2021
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23. SARS-CoV-2 Genomic Variation in Space and Time in Hospitalized Patients in Philadelphia

Author

Everett, John, primary, Hokama, Pascha, additional, Roche, Aoife M., additional, Reddy, Shantan, additional, Hwang, Young, additional, Kessler, Lyanna, additional, Glascock, Abigail, additional, Li, Yize, additional, Whelan, Jillian N., additional, Weiss, Susan R., additional, Sherrill-Mix, Scott, additional, McCormick, Kevin, additional, Whiteside, Samantha A., additional, Graham-Wooten, Jevon, additional, Khatib, Layla A., additional, Fitzgerald, Ayannah S., additional, Collman, Ronald G., additional, and Bushman, Frederic, additional

Published
2021
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25. CD19-targeting CAR T cell immunotherapy outcomes correlate with genomic modification by vector integration

Author

Nobles, Christopher L., primary, Sherrill-Mix, Scott, additional, Everett, John K., additional, Reddy, Shantan, additional, Fraietta, Joseph A., additional, Porter, David L., additional, Frey, Noelle, additional, Gill, Saar I., additional, Grupp, Stephan A., additional, Maude, Shannon L., additional, Siegel, Donald L., additional, Levine, Bruce L., additional, June, Carl H., additional, Lacey, Simon F., additional, Melenhorst, J. Joseph, additional, and Bushman, Frederic D., additional

Published
2019
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36. Vector Integration and Efficacy of CD19-Directed CAR T Cell Therapy in Acute Lymphoblastic Leukemia (ALL) and Chronic Lymphocytic Leukemia (CLL)

Author

Nobles, Christopher L, primary, Everett, John K, additional, Reddy, Shantan, additional, Fraietta, Joseph A, additional, Porter, David L., additional, Frey, Noelle V., additional, Grupp, Stephan A., additional, Siegel, Don L., additional, Lacey, Simon F, additional, June, Carl H, additional, Bushman, Frederic D, additional, and Melenhorst, J. Joseph, additional

Published
2018
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38. INSPIIRED: A Pipeline for Quantitative Analysis of Sites of New DNA Integration in Cellular Genomes

Author

Sherman, Eric, primary, Nobles, Christopher, additional, Berry, Charles C., additional, Six, Emmanuelle, additional, Wu, Yinghua, additional, Dryga, Anatoly, additional, Malani, Nirav, additional, Male, Frances, additional, Reddy, Shantan, additional, Bailey, Aubrey, additional, Bittinger, Kyle, additional, Everett, John K., additional, Caccavelli, Laure, additional, Drake, Mary J., additional, Bates, Paul, additional, Hacein-Bey-Abina, Salima, additional, Cavazzana, Marina, additional, and Bushman, Frederic D., additional

Published
2017
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39. Randomized Phase II Trial of Gemcitabine Plus TH-302 Versus Gemcitabine in Patients With Advanced Pancreatic Cancer

Author

Borad, Mitesh J., primary, Reddy, Shantan G., additional, Bahary, Nathan, additional, Uronis, Hope E., additional, Sigal, Darren, additional, Cohn, Allen L., additional, Schelman, William R., additional, Stephenson, Joe, additional, Chiorean, E. Gabriela, additional, Rosen, Peter J., additional, Ulrich, Brian, additional, Dragovich, Tomislav, additional, Del Prete, Salvatore A., additional, Rarick, Mark, additional, Eng, Clarence, additional, Kroll, Stew, additional, and Ryan, David P., additional

Published
2015
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40. Disruption of TET2promotes the therapeutic efficacy of CD19-targeted T cells

Author

Fraietta, Joseph, Nobles, Christopher, Sammons, Morgan, Lundh, Stefan, Carty, Shannon, Reich, Tyler, Cogdill, Alexandria, Morrissette, Jennifer, DeNizio, Jamie, Reddy, Shantan, Hwang, Young, Gohil, Mercy, Kulikovskaya, Irina, Nazimuddin, Farzana, Gupta, Minnal, Chen, Fang, Everett, John, Alexander, Katherine, Lin-Shiao, Enrique, Gee, Marvin, Liu, Xiaojun, Young, Regina, Ambrose, David, Wang, Yan, Xu, Jun, Jordan, Martha, Marcucci, Katherine, Levine, Bruce, Garcia, K., Zhao, Yangbing, Kalos, Michael, Porter, David, Kohli, Rahul, Lacey, Simon, Berger, Shelley, Bushman, Frederic, June, Carl, and Melenhorst, J.

Abstract

Cancer immunotherapy based on genetically redirecting T cells has been used successfully to treat B cell malignancies1–3. In this strategy, the T cell genome is modified by integration of viral vectors or transposons encoding chimaeric antigen receptors (CARs) that direct tumour cell killing. However, this approach is often limited by the extent of expansion and persistence of CAR T cells4,5. Here we report mechanistic insights from studies of a patient with chronic lymphocytic leukaemia treated with CAR T cells targeting the CD19 protein. Following infusion of CAR T cells, anti-tumour activity was evident in the peripheral blood, lymph nodes and bone marrow; this activity was accompanied by complete remission. Unexpectedly, at the peak of the response, 94% of CAR T cells originated from a single clone in which lentiviral vector-mediated insertion of the CAR transgene disrupted the methylcytosine dioxygenase TET2gene. Further analysis revealed a hypomorphic mutation in this patient’s second TET2allele. TET2-disrupted CAR T cells exhibited an epigenetic profile consistent with altered T cell differentiation and, at the peak of expansion, displayed a central memory phenotype. Experimental knockdown of TET2recapitulated the potency-enhancing effect of TET2dysfunction in this patient’s CAR T cells. These findings suggest that the progeny of a single CAR T cell induced leukaemia remission and that TET2 modification may be useful for improving immunotherapies. Genetically engineered T cells that induced remission in a patient with chronic lymphocytic leukaemia were found to have disruption of the TET2gene, which caused T cell changes that potentiated their anti-tumour effects.

Published
2018
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41. Age-related macular degeneration: current treatments

Author

Hubschman,Jean-Pierre, Reddy,Shantan, Schwartz,Steven D, Hubschman,Jean-Pierre, Reddy,Shantan, and Schwartz,Steven D

Abstract

Jean Pierre Hubschman, Shantan Reddy, Steven D SchwartzJules Stein Eye Institute, Department of Ophthalmology, University of California, David Geffen School of Medicine, Los Angeles, California, USAPurpose: Although important progress has been made in understanding age-related macular degeneration (AMD), management of the disease continues to be a challenge. AMD research has led to a widening of available treatment options and improved prognostic perspectives. This essay reviews these treatment options.Design: Interpretative essay.Methods: Literature review and interpretation.Results: Current treatments to preserve vision in patients with non-exudative AMD include antioxidant vitamins and mineral supplementations. Exudative AMD is currently most often treated monthly with anti-VEGF intra-vitreal injections. However, investigators are beginning to experiment with combination therapy and surgical approaches in an attempt to limit the number of treatment and reduce the financial burden on the health care system.Conclusion: By better understanding the basis and pathogenesis of AMD, newer therapies will continue to be developed that target specific pathways in patients with AMD, with the hoped for outcome of better management of the disease and improved visual acuity.Keywords: age-related macular degeneration, VEGF, photodynamic therapy, laser, surgery

Published
2009

42. Age-related macular degeneration: experimental and emerging treatments

Author

Hubschman,Jean-Pierre, Reddy,Shantan, Schwartz,Steven D, Hubschman,Jean-Pierre, Reddy,Shantan, and Schwartz,Steven D

Abstract

Jean Pierre Hubschman, Shantan Reddy, Steven D SchwartzJules Stein Eye Institute, Department of Ophthalmology, University of California, David Geffen School of Medicine, Los Angeles, California, USAPurpose: This essay reviews the experimental treatments and new imaging modalities that are currently being explored by investigators to help treat patients with age-related macular degeneration (AMD).Design: Interpretative essay.Methods: Literature review and interpretation.Results: Experimental treatments to preserve vision in patients with exudative AMD include blocking vascular endothelial growth factor (VEGF), binding VEGF, and modulating the VEGF receptors. Investigators are also attempting to block signal transduction with receptor tyrosine kinase inhibitors. Experimental treatments for non-exudative AMD include agents that target inflammation, oxidative stress, and implement immune-modulation. The effectiveness of these newer pharmacologic agents has the potential to grow exponentially when used in combination with new and improved imaging modalities that can help identify disease earlier and follow treatment response more precisely.Conclusion: With a better understanding, at the genetic and molecular level, of AMD and the development of superior imaging modalities, investigators are able to offer treatment options that may offer unprecedented visual gains while reducing the need for repetitive treatments.Keywords: age-related macular degeneration, VEGF, SiRNA, PEDF

Published
2009

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