Cold Spring Harbor perspectives in medicine Cold Spring Harbor perspectives in medicine RSS feedThis is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.

[PERSPECTIVES] Lessons Learned from the Development of the First FDA-Approved Gene Therapy Drug, Voretigene Neparvovec-rzyl
In the 5 years following U.S. Food and Drug Administration (FDA) approval of the first gene therapy reagent approved to treat a genetic disease, voretigene neparvovec-rzyl (Luxturna), retinal disease clinics, hospital pharmacies, operating rooms, and even health insurance entities around the world have incorporated gene therapy as a standard procedure. The success of Luxturna has helped pave the way to establish a template for developing other gene therapy reagents that promise to restore sight or halt the progression of photoreceptor cell loss in both inherited and acquired retinal diseases. Here we review lessons learned...
Source: Cold Spring Harbor perspectives in medicine - May 2, 2023 Category: Research Authors: Bennett, J., Maguire, A. M. Tags: Retinal Disorders: Genetic Approaches to Diagnosis and Treatment PERSPECTIVES Source Type: research

[PERSPECTIVES] Personalized Financial Planning Using Applied Genetics
Forthcoming advances in geroscience will influence the health span of current and future generations and generate both challenges and opportunities for those approaching or reaching retirement ages. The resulting changes in the life course will influence those reaching stages in life that are commonly associated with retirement. How people plan for that later phase of life is critical—especially given that current approaches to planning are either nonexistent or outdated. In this review, we show how advances in applied genetics can yield valuable information for individuals that are facing the challenges and opportun...
Source: Cold Spring Harbor perspectives in medicine - May 2, 2023 Category: Research Authors: Olshansky, S. J., Willcox, B., Ashburn, K., Stukey, J., Willcox, C. Tags: Aging PERSPECTIVES Source Type: research

[PERSPECTIVES] Immunotherapy Approaches for Breast Cancer Patients in 2023
Immunotherapy, particularly agents targeting the immunoregulatory PD-1/PD-L1 axis, harnesses the power of the immune system to treat cancer, with unique potential for a durable treatment effect due to immunologic memory. The PD-1 inhibitor pembrolizumab combined with neoadjuvant chemotherapy followed by adjuvant pembrolizumab improves event-free survival and is a new standard of care for high-risk, early-stage triple-negative breast cancer (TNBC), regardless of tumor PD-L1 expression. For metastatic TNBC, pembrolizumab combined with chemotherapy is a new standard of care for the first-line therapy of PD-L1+ metastatic TNBC...
Source: Cold Spring Harbor perspectives in medicine - April 3, 2023 Category: Research Authors: Emens, L. A., Loi, S. Tags: Breast Cancer: From Fundamental Biology to Therapeutic Strategies PERSPECTIVES Source Type: research

[PERSPECTIVES] Therapeutic Gene Editing in Inherited Retinal Disorders
Since the development of CRISPR/Cas9 gene editing in 2012, therapeutic editing research has produced several phase 1-2a trials. Here we provide an overview of the mechanisms and applications of various gene-editing technologies including adeno-associated virus vectors, lentiviruses, CRISPR/Cas9 systems, base and prime editing, antisense oligonucleotides, short-hairpin RNAs, Cas13, and adenosine deaminase acting on RNA for the treatment of various inherited retinal diseases (IRDs). We outline the various stages of clinical trials using these technologies and the impacts they have made in advancing the practice of medicine. ...
Source: Cold Spring Harbor perspectives in medicine - April 3, 2023 Category: Research Authors: Ling, J., Jenny, L. A., Zhou, A., Tsang, S. H. Tags: Retinal Disorders: Genetic Approaches to Diagnosis and Treatment PERSPECTIVES Source Type: research

[PERSPECTIVES] Biological Restraints on Indefinite Survival
Multiple observations that organismal life span can be extended by nutritional, genetic, or pharmacological intervention has raised the prospect of transforming medicine with the goal of slowing, stopping, or even reversing age-associated disease and maintaining or restoring health and resilience in the increasing numbers of elderly across the world. The potential for such an enterprise is supported in theory by plant and animal models of negligible senescence, most notably the small, freshwater organism Hydra spp. The existence of some very long-lived species, including bowhead whale, Greenland shark, and giant tortoises,...
Source: Cold Spring Harbor perspectives in medicine - April 3, 2023 Category: Research Authors: Vijg, J., Austad, S. N. Tags: Aging PERSPECTIVES Source Type: research

[PERSPECTIVES] Extracellular Matrix Regulation of Vascular Morphogenesis, Maturation, and Stabilization
The extracellular matrix represents a critical regulator of tissue vascularization during embryonic development and postnatal life. In this perspective, we present key information and concepts that focus on how the extracellular matrix controls capillary assembly, maturation, and stabilization, and, in addition, contributes to tissue stability and health. In particular, we present and discuss mechanistic details underlying (1) the role of the extracellular matrix in controlling different steps of vascular morphogenesis, (2) the ability of endothelial cells (ECs) and pericytes to coassemble into elongated and narrow capilla...
Source: Cold Spring Harbor perspectives in medicine - April 3, 2023 Category: Research Authors: Davis, G. E., Kemp, S. S. Tags: Angiogenesis PERSPECTIVES Source Type: research

[PERSPECTIVES] Beyond the NEI-VFQ: Recent Experience in the Development and Utilization of Patient-Reported Outcomes for Inherited Retinal Diseases
Patient-reported outcome measures (PROMs) are tools designed to capture how a patient feels or functions, without the input or interpretation of anyone else. The earliest PROMs used in studies of inherited retinal diseases (IRDs) lack the validity required for therapy development today. The NEI-VFQ was one of the earliest PROMs developed using concept elicitation and cognitive debriefing of patients, but it lacks items that are common to patients with IRDs and it has poor measurement properties. Recent advances in PROM development include the Michigan Retinal Degeneration Questionnaire (MRDQ) and the ViSIO-PRO for nonsyndr...
Source: Cold Spring Harbor perspectives in medicine - March 1, 2023 Category: Research Authors: Durham, T., Banhazi, J., Patalano, F., Jayasundera, T. Tags: Retinal Disorders: Genetic Approaches to Diagnosis and Treatment PERSPECTIVES Source Type: research

[PERSPECTIVES] The Importance of Natural History Studies in Inherited Retinal Diseases
Natural history studies of inherited retinal diseases (IRDs) play a critical role in the design and implementation of treatment trials. Study objectives ideally encompass (1) understanding the time course and pattern of disease progression, (2) within genotypic and phenotypic subtypes of patient populations, and (3) characterizing a range of measures of vision function, retinal structure, and functional vision that may serve as endpoints. In rare disease, data quality standards are paramount to optimizing smaller sample sizes, including a prospective, standardized, and longitudinal approach to data collection. Multicenter ...
Source: Cold Spring Harbor perspectives in medicine - March 1, 2023 Category: Research Authors: Ayala, A., Cheetham, J., Durham, T., Maguire, M. Tags: Retinal Disorders: Genetic Approaches to Diagnosis and Treatment PERSPECTIVES Source Type: research

[PERSPECTIVES] Endothelial Cell-Pericyte Interactions in the Pathogenesis of Cerebral Cavernous Malformations (CCMs)
Cerebral cavernous malformations (CCMs), consisting of multiple, dilated capillary channels formed by a single layer of endothelium and lacking parenchymal cells, are exclusively to the brain. Patients with inherited autosomal-dominant CCMs carry loss-of-function mutations in one of three genes: CCM1, CCM2, and CCM3. It is not known why CCM lesions are confined to brain vasculature despite the ubiquitous expression of CCM proteins in all tissues, and whether cell types other than endothelial cells (ECs) contribute to CCM lesion formation. The prevailing view is that the primary defects in CCMs in humans are EC-intrinsic, s...
Source: Cold Spring Harbor perspectives in medicine - March 1, 2023 Category: Research Authors: Min, W., Zhou, J. H. Tags: Angiogenesis PERSPECTIVES Source Type: research

[PERSPECTIVES] Targeting Angiogenesis via Resolution of Inflammation
Angiogenesis, the growth of new blood vessels, plays a critical role in tissue repair and regeneration, as well as in cancer. A paradigm shift is emerging in our understanding of the resolution of inflammation as an active biochemical process with the discovery of novel endogenous specialized pro-resolving mediators (SPMs), including resolvins. Angiogenesis and the resolution of inflammation are critical interdependent processes. Disrupted inflammation resolution can accelerate tumor growth, which is angiogenesis-dependent. SPMs, including resolvins and lipoxins, inhibit physiologic and pathological angiogenesis at nanogra...
Source: Cold Spring Harbor perspectives in medicine - March 1, 2023 Category: Research Authors: Kelly, A. G., Panigrahy, D. Tags: Angiogenesis PERSPECTIVES Source Type: research

[PERSPECTIVES] Photoreceptor Cell Replacement Using Pluripotent Stem Cells: Current Knowledge and Remaining Questions
Retinal degeneration is an increasing global burden without cure for the majority of patients. Once retinal cells have degenerated, vision is permanently lost. Different strategies have been developed in recent years to prevent retinal degeneration or to restore sight (e.g., gene therapy, cell therapy, and electronic implants). Herein, we present current treatment strategies with a focus on cell therapy for photoreceptor replacement using human pluripotent stem cells. We will describe the state of the art and discuss obstacles and limitations observed in preclinical animal models as well as future directions to improve gra...
Source: Cold Spring Harbor perspectives in medicine - February 1, 2023 Category: Research Authors: Monville, C., Goureau, O., Ben M'Barek, K. Tags: Retinal Disorders: Genetic Approaches to Diagnosis and Treatment PERSPECTIVES Source Type: research

[PERSPECTIVES] International Gains to Achieving Healthy Longevity
Utilizing economic tools, we evaluate the gains from improving the relationship between biological and chronological age in dollar terms. We show that the gains to individuals are substantial because targeting aging exploits synergies between health and life expectancy and the complementarities across different diseases. Gains are boosted by improvements in life expectancy and a rising number of older people. We compute the value of slowing aging in a range of countries and estimate that increasing life expectancy by 1 year has an annual benefit of ~4%–5% of gross domestic product (GDP). Augmenting GDP with these mea...
Source: Cold Spring Harbor perspectives in medicine - February 1, 2023 Category: Research Authors: Scott, A., Ashwin, J., Ellison, M., Sinclair, D. Tags: Aging PERSPECTIVES Source Type: research

[PERSPECTIVES] Lymphatic Clearance and Pump Function
Lymphatic vessels have an active role in draining excess interstitial fluid from organs and serving as conduits for immune cell trafficking to lymph nodes. In the central circulation, the force needed to propel blood forward is generated by the heart. In contrast, lymphatic vessels rely on intrinsic vessel contractions in combination with extrinsic forces for lymph propulsion. The intrinsic pumping features phasic contractions generated by lymphatic smooth muscle. Periodic, bicuspid valves composed of endothelial cells prevent backflow of lymph. This work provides a brief overview of lymph transport, including initial lymp...
Source: Cold Spring Harbor perspectives in medicine - February 1, 2023 Category: Research Authors: Breslin, J. W. Tags: Angiogenesis PERSPECTIVES Source Type: research

[PERSPECTIVES] Notch Signaling in the Vasculature: Angiogenesis and Angiocrine Functions
Formation of a functional blood vessel network is a complex process tightly controlled by pro- and antiangiogenic signals released within the local microenvironment or delivered through the bloodstream. Endothelial cells precisely integrate such temporal and spatial changes in extracellular signals and generate an orchestrated response by modulating signaling transduction, gene expression, and metabolism. A key regulator in vessel formation is Notch signaling, which controls endothelial cell specification, proliferation, migration, adhesion, and arteriovenous differentiation. This review summarizes the molecular biology of...
Source: Cold Spring Harbor perspectives in medicine - February 1, 2023 Category: Research Authors: Hasan, S. S., Fischer, A. Tags: Angiogenesis PERSPECTIVES Source Type: research

[PERSPECTIVES] Retinal Degeneration Animal Models in Bardet-Biedl Syndrome and Related Ciliopathies
Retinal degeneration due to photoreceptor ciliary-related proteins dysfunction accounts for more than 25% of all inherited retinal dystrophies. The cilium, being an evolutionarily conserved and ubiquitous organelle implied in many cellular functions, can be investigated by way of many models from invertebrate models to nonhuman primates, all these models have massively contributed to the pathogenesis understanding of human ciliopathies. Taking the Bardet–Biedl syndrome (BBS) as an emblematic example as well as other related syndromic ciliopathies, the contribution of a wide range of models has enabled to characterize...
Source: Cold Spring Harbor perspectives in medicine - January 3, 2023 Category: Research Authors: Delvallee, C., Dollfus, H. Tags: Retinal Disorders: Genetic Approaches to Diagnosis and Treatment PERSPECTIVES Source Type: research