Background
Harvard Precision Medicine -2018 Symposium in June was concluded with a wakening ta... more Background
Harvard Precision Medicine -2018 Symposium in June was concluded with a wakening take-home message: bridge phenotype gaps in medicine: “Biology”; clinicians/surgeons and all parties involved in medicine development and practice must change from
procedure-based medicine to biology-based medicine in the 21st century modern times. In ophthalmic therapeutic innovation, this topic becomes even more important in the new era of pharmacotherapy for ocular diseases and medicine precision. This editorial
insights shed light on the root cause of CyPass safety recall (by Alcon/Novartis) and risk mitigation strategy, which helps deepen a better understanding of glaucoma disease biology in the surgical intervention for early and late stage of glaucoma. Specifically, emphasizing the role of metabolic inflammation and oxidative damage in glaucoma pathological processes opens a broader perspective on improvement of the disease management and therapeutic algorithm toward precision medicine.
Introduction:
2017 is an exciting year made a landmark in gene therapy. Spark Therapeutics recei... more Introduction:
2017 is an exciting year made a landmark in gene therapy. Spark Therapeutics received FDA advisory committee approval of hRPE65 gene therapy for patients with LCA2 (Lebers Congenital Amaurosis) [1]. It took 20-year winded journey to establish a viable clinical regulatory path forward, during which period gene therapy paradigm has evolved from classic gene replacement to using genetic engineer as drug delivery tool and optogenetics to address various stages of neurovascular problems in the retina. The youngest birth is CRISPR based gene editing technology, which is dancing on a new wave of precision medicine. With overarching new technologies across broad disciplines, things will move faster with better results. There are a few important subjects that are under-appreciated which could stumble the field.
Abstract
Albert Einstein once noted: “If I had only one hour to save the world, I would spend fi... more Abstract
Albert Einstein once noted: “If I had only one hour to save the world, I would spend fifty-five minutes defining the problem, and only five minutes finding the solution”. In medicine development, the process of defining that question is about identifying the “entry point
or break point or gap” for next steps. The success of drug discovery and development is built upon decades of deep scientific research and clinical evidences, through back-and-forth development & validation of the integrative sciences, and takes cross-functional team efforts. This review is to address some of the key issues in clinical trials and translational gaps, what we can do to improve, and which areas are the technology limitations or disease inherited problems that we do not yet have the leverage to navigate. Specifically, the author emphasizes the importance of drug molecular mechanism match precision in target disease indication, which is the scientific basis of product medical strategy for improving clinical translational efficiency in early and late stage drug development. Retina and glaucoma therapeutic targets are the key highlights. Closing remarks elevate the content to the strategic leadership and talent skill set that helps to define the future of medicine development path.
Introduction: Trabodenoson is an adenosine mimetic acting selectively at the A1 receptor (A1R) su... more Introduction: Trabodenoson is an adenosine mimetic acting selectively at the A1 receptor (A1R) subtype, involved in multiple signaling pathways including matrix metalloproteinase (MMP-2) associated with glaucoma pathological processes. It has been developed as a Phase 3 candidate for the treatment of patients with primary open-angle glaucoma (POAG) or ocular hypertension (OH). Area Covered: This review summarizes the molecular traits of Trabodenoson in intraocular pressure (IOP) regulations and provides a scientific interpretation of the Phase 2 clinical study results. This article sheds light on the root causes of the two pivotal Phase 3 clinical trial failures in patients with POAG or OH; it further highlights the discovery of MMP-2 in trabecular meshwork (TM) rejuvenation, which has strategic importance in long-term glaucoma patient care. Expert Opinion: Trabodenoson is a BID glaucoma eye drop with a possible QD dose as maintenance. Its Phase 3 pivotal clinical trials failed at the wrong dose and dosing regimen because of the misinterpretation of the complex IOP results from the Phase 2 monotherapy and combination studies. The future development should focus on the TM benefits whilst unleashing its potential of neural protection through nanoparticle eye drops, medical coating, and sustained release drug delivery.
Modern medicine development is alike unlocking mystery of black box. The journey of 10- year drug... more Modern medicine development is alike unlocking mystery of black box. The journey of 10- year drug development is about establishing a drug molecular biological trait along with its pharmacological behaviors in animal disease models and various human conditions. Product medical strategy has become ever more important in bridging gaps for translational efficiency. This review focuses on the paradigm shift of therapeutic intervention for retinal diseases. Topics include: 1) Emerging ocular drug delivery innovation from polymer-based sustained-release drug delivery to genetic engineering protein biofactory (superachoroidal and subretinal routes begin to merge). 2) New themes of tissue rejuvenation and parainflammation in retina and glaucoma disease management. 3) New highs in disease alteration by emerging therapies - the switch from “wet to dry” vascular AMD (age-related macular degeneration) is a great example of such in the new era of anti-VEGF therapy. 4) Bio-therapeutic innovation ...
The use of human embryonic stem cell (hESC)-derived Retinal Pigment Epithelium (RPE) transplants ... more The use of human embryonic stem cell (hESC)-derived Retinal Pigment Epithelium (RPE) transplants has advanced dramatically in different forms for clinical application in macular degeneration. This review focuses on the first generation of hESC-RPE cell line, named as “MA09-hRPE” by Astellas Institute of Regenerative Medicine (AIRM), and its therapeutic application in human, which evaluated the safety and efficacy of MA09-hRPE cell line transplanted in patients with macular degeneration. This project marks the first milestone in overcoming ethical hurdles and oncogenic safety concerns associated with the use of an embryonic stem cell-derived line. Through in-depth, evidence-based analysis of the MA09-hRPE cell line, along with other hESC-RPE cell lines, this review aims to draw attention to the key technical challenges pertinent to the generation of a biologically competent hESC-RPE cell line and distill the four key prognostic factors residing in the host retina, which concurrently ...
Ocriplasmin is a proteolytic enzyme that digests laminin, fibronectin, and collagen IV. In the ve... more Ocriplasmin is a proteolytic enzyme that digests laminin, fibronectin, and collagen IV. In the vertebrate retina, Muller glial terminals form the key component of vitreoretinal interface, namely Inner Limiting Membrane (ILM), of which laminin enriches its extracellular matrix. Moreover, Muller glia serves as “living optical fiber” and antenna that collects external light from cornea and transmits it through the neurosensory layer towards the photoreceptors, where the visual process and refinement begins [3]. When ocriplasmin is injected into the vitreous cavity, ILM acts as the very first biologic defense and drug delivery barrier. If the retina were overexposed to this enzyme, the integrity of Muller glia terminals will be first compromised. However, Muller glia is the only structure cell within the retina that has the ability to regenerate and regrow following injury, which may explain why such vision disturbance is reversible, gradual and time-dependent. From ERG point of view, M...
Existing animal models of choroidal neovascularization (CNV) present several problems: they are h... more Existing animal models of choroidal neovascularization (CNV) present several problems: they are hard to reproduce, they are inefficient, and the CNV created is not sustainable. The purpose of this study is to develop a highly efficient, reliable, sustainable rabbit model of CNV to facilitate the study of anti-angiogenic and anti-proliferative therapies for ocular diseases. Twenty-two pigmented rabbits were used in this study. Eleven rabbits received subretinal injections of either 10 ml of Matrigel with 500 ng of vascular endothelial growth factor (VEGF) or 20 ml of Matrigel with 750 ng of VEGF; eight rabbits received subretinal injections of either 10 or 20 ml of Matrigel only; three rabbits used as controls received subretinal injections of 20 ml phosphate-buffered saline (PBS) alone. Fundus photography, fluorescein angiography, optical coherence tomography, and histologic examinations were performed 1, 2, 4, and 9 weeks after injection. All experimental eyes showed angiographic leakage within this localized area 1 week after injection. The amount of leakage usually increased at weeks 2 and 4 and, in most cases, persisted at week 9. Control eyes demonstrated no leakage at any time point. Optical coherence tomography of treated eyes showed subretinal fluid and the presence of a lesion, possibly vascular or fibrotic, at the site of the leakage. Histologic analysis confirmed the presence of new subretinal blood vessels in the areas of Matrigel deposit. In conclusion, this novel method provides a highly reproducible, reliable, and sustainable rabbit model of experimental choroidal neovascularization. Such a model may prove useful for screening new anti-angiogenic therapies in a larger animal eye.
Rescula (unoprostone isopropyl) has been in the market as ocular hypotensive drug since 1994. The... more Rescula (unoprostone isopropyl) has been in the market as ocular hypotensive drug since 1994. There are amounting scientific research and post-marketing clinical experiences reported in peer review journals. Yet there seems limited understanding about its unique clinical implication associated with newly discovered molecular mechanism (traits) of BK channel activation. Hence this review article is using a focal lens with an eye on B-K channel activation to further delineate possible roles of rescula in modulating chronic parainflammation in the eye, which may eventually set it apart from the rest lipid hypotensive drugs such as latanoprost that is pro-inflammatory in nature. Cystoid macular edema and refractory glaucoma will be the key historical clinical case highlights.
Modern medicine development is alike unlocking mystery of black box. The journey of 10-year drug ... more Modern medicine development is alike unlocking mystery of black box. The journey of 10-year drug development is about establishing a drug molecular biological trait along with its pharmacological behaviors in animal disease models and various human conditions. Product medical strategy has become ever more important in bridging gaps for translational efficiency. This review focuses on the paradigm shift of therapeutic intervention for retinal diseases. Topics include: 1) Emerging ocular drug delivery innovation from polymer-based sustained-release drug delivery to genetic engineering protein biofactory (superachoroidal and subretinal routes begin to merge). 2) New themes of tissue rejuvenation and parainflammation in retina and glaucoma disease management. 3) New highs in disease alteration by emerging therapies-the switch from " wet to dry " vascular AMD (age-related macular degeneration) is a great example of such in the new era of anti-VEGF therapy. 4) Bio-therapeutic innovation at a glance. 5) Understand disease staging and phenotype stratification is " A Must " in developing personalized treatment algorithm. New evidences suggest that AMD represents a group of heterogeneous clinical pathological entity that includes RPE aging, photoreceptor loss, Bruch's membrane thickening, and choroid ischemia, among which one or more can be the primary trigger and predominant clinical phenotype. New appreciation of glaucoma as a neural degenerative disease involving pressure-dependent and pressure-independent risk factors may lead to breakthrough of neural protection drug development in the 21 st century. In summary, reduce photoreceptor and retinal gan-glion cell loss is the ultimate goal of therapeutic intervention for a large spectrum of significant neurovascular diseases in the retina. (254 words). In the retina, there are two biggest problems spanning at two extreme ends. One end is about cell proliferation such as choroid neo-vascularization (CNV), proliferative vitraretinopathy (PVR), proliferative diabetic retinopathy (PDR), epiretinal or subretinal fibrosis and scar formation, as well as inflammatory cell proliferation. The other end is abnormal cell loss due to apoptotic and necrotic cell death in various genetic or acquired pathological conditions, such as age-related macular degeneration (AMD), glaucomatous neural degeneration, retinitis pigmentosa (RP) and Stargardt's macular degeneration (SMD), for which regenerative medicine comes into a play. In the past two decades, scientific advances have allowed us to gain in-depth understanding of molecular pathophysiological mechanisms involved retinal diseases, which are changing the way of how we treat patient and how we project future medicine.
Background
Harvard Precision Medicine -2018 Symposium in June was concluded with a wakening ta... more Background
Harvard Precision Medicine -2018 Symposium in June was concluded with a wakening take-home message: bridge phenotype gaps in medicine: “Biology”; clinicians/surgeons and all parties involved in medicine development and practice must change from
procedure-based medicine to biology-based medicine in the 21st century modern times. In ophthalmic therapeutic innovation, this topic becomes even more important in the new era of pharmacotherapy for ocular diseases and medicine precision. This editorial
insights shed light on the root cause of CyPass safety recall (by Alcon/Novartis) and risk mitigation strategy, which helps deepen a better understanding of glaucoma disease biology in the surgical intervention for early and late stage of glaucoma. Specifically, emphasizing the role of metabolic inflammation and oxidative damage in glaucoma pathological processes opens a broader perspective on improvement of the disease management and therapeutic algorithm toward precision medicine.
Introduction:
2017 is an exciting year made a landmark in gene therapy. Spark Therapeutics recei... more Introduction:
2017 is an exciting year made a landmark in gene therapy. Spark Therapeutics received FDA advisory committee approval of hRPE65 gene therapy for patients with LCA2 (Lebers Congenital Amaurosis) [1]. It took 20-year winded journey to establish a viable clinical regulatory path forward, during which period gene therapy paradigm has evolved from classic gene replacement to using genetic engineer as drug delivery tool and optogenetics to address various stages of neurovascular problems in the retina. The youngest birth is CRISPR based gene editing technology, which is dancing on a new wave of precision medicine. With overarching new technologies across broad disciplines, things will move faster with better results. There are a few important subjects that are under-appreciated which could stumble the field.
Abstract
Albert Einstein once noted: “If I had only one hour to save the world, I would spend fi... more Abstract
Albert Einstein once noted: “If I had only one hour to save the world, I would spend fifty-five minutes defining the problem, and only five minutes finding the solution”. In medicine development, the process of defining that question is about identifying the “entry point
or break point or gap” for next steps. The success of drug discovery and development is built upon decades of deep scientific research and clinical evidences, through back-and-forth development & validation of the integrative sciences, and takes cross-functional team efforts. This review is to address some of the key issues in clinical trials and translational gaps, what we can do to improve, and which areas are the technology limitations or disease inherited problems that we do not yet have the leverage to navigate. Specifically, the author emphasizes the importance of drug molecular mechanism match precision in target disease indication, which is the scientific basis of product medical strategy for improving clinical translational efficiency in early and late stage drug development. Retina and glaucoma therapeutic targets are the key highlights. Closing remarks elevate the content to the strategic leadership and talent skill set that helps to define the future of medicine development path.
Introduction: Trabodenoson is an adenosine mimetic acting selectively at the A1 receptor (A1R) su... more Introduction: Trabodenoson is an adenosine mimetic acting selectively at the A1 receptor (A1R) subtype, involved in multiple signaling pathways including matrix metalloproteinase (MMP-2) associated with glaucoma pathological processes. It has been developed as a Phase 3 candidate for the treatment of patients with primary open-angle glaucoma (POAG) or ocular hypertension (OH). Area Covered: This review summarizes the molecular traits of Trabodenoson in intraocular pressure (IOP) regulations and provides a scientific interpretation of the Phase 2 clinical study results. This article sheds light on the root causes of the two pivotal Phase 3 clinical trial failures in patients with POAG or OH; it further highlights the discovery of MMP-2 in trabecular meshwork (TM) rejuvenation, which has strategic importance in long-term glaucoma patient care. Expert Opinion: Trabodenoson is a BID glaucoma eye drop with a possible QD dose as maintenance. Its Phase 3 pivotal clinical trials failed at the wrong dose and dosing regimen because of the misinterpretation of the complex IOP results from the Phase 2 monotherapy and combination studies. The future development should focus on the TM benefits whilst unleashing its potential of neural protection through nanoparticle eye drops, medical coating, and sustained release drug delivery.
Modern medicine development is alike unlocking mystery of black box. The journey of 10- year drug... more Modern medicine development is alike unlocking mystery of black box. The journey of 10- year drug development is about establishing a drug molecular biological trait along with its pharmacological behaviors in animal disease models and various human conditions. Product medical strategy has become ever more important in bridging gaps for translational efficiency. This review focuses on the paradigm shift of therapeutic intervention for retinal diseases. Topics include: 1) Emerging ocular drug delivery innovation from polymer-based sustained-release drug delivery to genetic engineering protein biofactory (superachoroidal and subretinal routes begin to merge). 2) New themes of tissue rejuvenation and parainflammation in retina and glaucoma disease management. 3) New highs in disease alteration by emerging therapies - the switch from “wet to dry” vascular AMD (age-related macular degeneration) is a great example of such in the new era of anti-VEGF therapy. 4) Bio-therapeutic innovation ...
The use of human embryonic stem cell (hESC)-derived Retinal Pigment Epithelium (RPE) transplants ... more The use of human embryonic stem cell (hESC)-derived Retinal Pigment Epithelium (RPE) transplants has advanced dramatically in different forms for clinical application in macular degeneration. This review focuses on the first generation of hESC-RPE cell line, named as “MA09-hRPE” by Astellas Institute of Regenerative Medicine (AIRM), and its therapeutic application in human, which evaluated the safety and efficacy of MA09-hRPE cell line transplanted in patients with macular degeneration. This project marks the first milestone in overcoming ethical hurdles and oncogenic safety concerns associated with the use of an embryonic stem cell-derived line. Through in-depth, evidence-based analysis of the MA09-hRPE cell line, along with other hESC-RPE cell lines, this review aims to draw attention to the key technical challenges pertinent to the generation of a biologically competent hESC-RPE cell line and distill the four key prognostic factors residing in the host retina, which concurrently ...
Ocriplasmin is a proteolytic enzyme that digests laminin, fibronectin, and collagen IV. In the ve... more Ocriplasmin is a proteolytic enzyme that digests laminin, fibronectin, and collagen IV. In the vertebrate retina, Muller glial terminals form the key component of vitreoretinal interface, namely Inner Limiting Membrane (ILM), of which laminin enriches its extracellular matrix. Moreover, Muller glia serves as “living optical fiber” and antenna that collects external light from cornea and transmits it through the neurosensory layer towards the photoreceptors, where the visual process and refinement begins [3]. When ocriplasmin is injected into the vitreous cavity, ILM acts as the very first biologic defense and drug delivery barrier. If the retina were overexposed to this enzyme, the integrity of Muller glia terminals will be first compromised. However, Muller glia is the only structure cell within the retina that has the ability to regenerate and regrow following injury, which may explain why such vision disturbance is reversible, gradual and time-dependent. From ERG point of view, M...
Existing animal models of choroidal neovascularization (CNV) present several problems: they are h... more Existing animal models of choroidal neovascularization (CNV) present several problems: they are hard to reproduce, they are inefficient, and the CNV created is not sustainable. The purpose of this study is to develop a highly efficient, reliable, sustainable rabbit model of CNV to facilitate the study of anti-angiogenic and anti-proliferative therapies for ocular diseases. Twenty-two pigmented rabbits were used in this study. Eleven rabbits received subretinal injections of either 10 ml of Matrigel with 500 ng of vascular endothelial growth factor (VEGF) or 20 ml of Matrigel with 750 ng of VEGF; eight rabbits received subretinal injections of either 10 or 20 ml of Matrigel only; three rabbits used as controls received subretinal injections of 20 ml phosphate-buffered saline (PBS) alone. Fundus photography, fluorescein angiography, optical coherence tomography, and histologic examinations were performed 1, 2, 4, and 9 weeks after injection. All experimental eyes showed angiographic leakage within this localized area 1 week after injection. The amount of leakage usually increased at weeks 2 and 4 and, in most cases, persisted at week 9. Control eyes demonstrated no leakage at any time point. Optical coherence tomography of treated eyes showed subretinal fluid and the presence of a lesion, possibly vascular or fibrotic, at the site of the leakage. Histologic analysis confirmed the presence of new subretinal blood vessels in the areas of Matrigel deposit. In conclusion, this novel method provides a highly reproducible, reliable, and sustainable rabbit model of experimental choroidal neovascularization. Such a model may prove useful for screening new anti-angiogenic therapies in a larger animal eye.
Rescula (unoprostone isopropyl) has been in the market as ocular hypotensive drug since 1994. The... more Rescula (unoprostone isopropyl) has been in the market as ocular hypotensive drug since 1994. There are amounting scientific research and post-marketing clinical experiences reported in peer review journals. Yet there seems limited understanding about its unique clinical implication associated with newly discovered molecular mechanism (traits) of BK channel activation. Hence this review article is using a focal lens with an eye on B-K channel activation to further delineate possible roles of rescula in modulating chronic parainflammation in the eye, which may eventually set it apart from the rest lipid hypotensive drugs such as latanoprost that is pro-inflammatory in nature. Cystoid macular edema and refractory glaucoma will be the key historical clinical case highlights.
Modern medicine development is alike unlocking mystery of black box. The journey of 10-year drug ... more Modern medicine development is alike unlocking mystery of black box. The journey of 10-year drug development is about establishing a drug molecular biological trait along with its pharmacological behaviors in animal disease models and various human conditions. Product medical strategy has become ever more important in bridging gaps for translational efficiency. This review focuses on the paradigm shift of therapeutic intervention for retinal diseases. Topics include: 1) Emerging ocular drug delivery innovation from polymer-based sustained-release drug delivery to genetic engineering protein biofactory (superachoroidal and subretinal routes begin to merge). 2) New themes of tissue rejuvenation and parainflammation in retina and glaucoma disease management. 3) New highs in disease alteration by emerging therapies-the switch from " wet to dry " vascular AMD (age-related macular degeneration) is a great example of such in the new era of anti-VEGF therapy. 4) Bio-therapeutic innovation at a glance. 5) Understand disease staging and phenotype stratification is " A Must " in developing personalized treatment algorithm. New evidences suggest that AMD represents a group of heterogeneous clinical pathological entity that includes RPE aging, photoreceptor loss, Bruch's membrane thickening, and choroid ischemia, among which one or more can be the primary trigger and predominant clinical phenotype. New appreciation of glaucoma as a neural degenerative disease involving pressure-dependent and pressure-independent risk factors may lead to breakthrough of neural protection drug development in the 21 st century. In summary, reduce photoreceptor and retinal gan-glion cell loss is the ultimate goal of therapeutic intervention for a large spectrum of significant neurovascular diseases in the retina. (254 words). In the retina, there are two biggest problems spanning at two extreme ends. One end is about cell proliferation such as choroid neo-vascularization (CNV), proliferative vitraretinopathy (PVR), proliferative diabetic retinopathy (PDR), epiretinal or subretinal fibrosis and scar formation, as well as inflammatory cell proliferation. The other end is abnormal cell loss due to apoptotic and necrotic cell death in various genetic or acquired pathological conditions, such as age-related macular degeneration (AMD), glaucomatous neural degeneration, retinitis pigmentosa (RP) and Stargardt's macular degeneration (SMD), for which regenerative medicine comes into a play. In the past two decades, scientific advances have allowed us to gain in-depth understanding of molecular pathophysiological mechanisms involved retinal diseases, which are changing the way of how we treat patient and how we project future medicine.
Uploads
Papers by Tina Qiu
Harvard Precision Medicine -2018 Symposium in June was concluded with a wakening take-home message: bridge phenotype gaps in medicine: “Biology”; clinicians/surgeons and all parties involved in medicine development and practice must change from
procedure-based medicine to biology-based medicine in the 21st century modern times. In ophthalmic therapeutic innovation, this topic becomes even more important in the new era of pharmacotherapy for ocular diseases and medicine precision. This editorial
insights shed light on the root cause of CyPass safety recall (by Alcon/Novartis) and risk mitigation strategy, which helps deepen a better understanding of glaucoma disease biology in the surgical intervention for early and late stage of glaucoma. Specifically, emphasizing the role of metabolic inflammation and oxidative damage in glaucoma pathological processes opens a broader perspective on improvement of the disease management and therapeutic algorithm toward precision medicine.
2017 is an exciting year made a landmark in gene therapy. Spark Therapeutics received FDA advisory committee approval of hRPE65 gene therapy for patients with LCA2 (Lebers Congenital Amaurosis) [1]. It took 20-year winded journey to establish a viable clinical regulatory path forward, during which period gene therapy paradigm has evolved from classic gene replacement to using genetic engineer as drug delivery tool and optogenetics to address various stages of neurovascular problems in the retina. The youngest birth is CRISPR based gene editing technology, which is dancing on a new wave of precision medicine. With overarching new technologies across broad disciplines, things will move faster with better results. There are a few important subjects that are under-appreciated which could stumble the field.
Albert Einstein once noted: “If I had only one hour to save the world, I would spend fifty-five minutes defining the problem, and only five minutes finding the solution”. In medicine development, the process of defining that question is about identifying the “entry point
or break point or gap” for next steps. The success of drug discovery and development is built upon decades of deep scientific research and clinical evidences, through back-and-forth development & validation of the integrative sciences, and takes cross-functional team efforts. This review is to address some of the key issues in clinical trials and translational gaps, what we can do to improve, and which areas are the technology limitations or disease inherited problems that we do not yet have the leverage to navigate. Specifically, the author emphasizes the importance of drug molecular mechanism match precision in target disease indication, which is the scientific basis of product medical strategy for improving clinical translational efficiency in early and late stage drug development. Retina and glaucoma therapeutic targets are the key highlights. Closing remarks elevate the content to the strategic leadership and talent skill set that helps to define the future of medicine development path.
Harvard Precision Medicine -2018 Symposium in June was concluded with a wakening take-home message: bridge phenotype gaps in medicine: “Biology”; clinicians/surgeons and all parties involved in medicine development and practice must change from
procedure-based medicine to biology-based medicine in the 21st century modern times. In ophthalmic therapeutic innovation, this topic becomes even more important in the new era of pharmacotherapy for ocular diseases and medicine precision. This editorial
insights shed light on the root cause of CyPass safety recall (by Alcon/Novartis) and risk mitigation strategy, which helps deepen a better understanding of glaucoma disease biology in the surgical intervention for early and late stage of glaucoma. Specifically, emphasizing the role of metabolic inflammation and oxidative damage in glaucoma pathological processes opens a broader perspective on improvement of the disease management and therapeutic algorithm toward precision medicine.
2017 is an exciting year made a landmark in gene therapy. Spark Therapeutics received FDA advisory committee approval of hRPE65 gene therapy for patients with LCA2 (Lebers Congenital Amaurosis) [1]. It took 20-year winded journey to establish a viable clinical regulatory path forward, during which period gene therapy paradigm has evolved from classic gene replacement to using genetic engineer as drug delivery tool and optogenetics to address various stages of neurovascular problems in the retina. The youngest birth is CRISPR based gene editing technology, which is dancing on a new wave of precision medicine. With overarching new technologies across broad disciplines, things will move faster with better results. There are a few important subjects that are under-appreciated which could stumble the field.
Albert Einstein once noted: “If I had only one hour to save the world, I would spend fifty-five minutes defining the problem, and only five minutes finding the solution”. In medicine development, the process of defining that question is about identifying the “entry point
or break point or gap” for next steps. The success of drug discovery and development is built upon decades of deep scientific research and clinical evidences, through back-and-forth development & validation of the integrative sciences, and takes cross-functional team efforts. This review is to address some of the key issues in clinical trials and translational gaps, what we can do to improve, and which areas are the technology limitations or disease inherited problems that we do not yet have the leverage to navigate. Specifically, the author emphasizes the importance of drug molecular mechanism match precision in target disease indication, which is the scientific basis of product medical strategy for improving clinical translational efficiency in early and late stage drug development. Retina and glaucoma therapeutic targets are the key highlights. Closing remarks elevate the content to the strategic leadership and talent skill set that helps to define the future of medicine development path.