Summary: 350 million people worldwide are believed to suffer from blinding diseases including age-related macular degeneration and diabetic retinopathy.
Researchers have discovered small-molecule drugs that could be used to treat age-related macular degeneration, diabetic retinopathy, and retinitis pigmentosa. The drugs, called stress resilience-enhancing drugs (SREDs), slowed or halted the progression of retinopathies in animal models by inhibiting cyclic nucleotide phosphodiesterases.
Key Facts:
Source: UC Irvine
In a University of California, Irvine-led study, researchers have discovered small-molecule drugs with potential clinical utility in the treatment of age-related macular degeneration (AMD), diabetic retinopathy (DR), and retinitis pigmentosa (RP).
The study, titled, Stress resilience-enhancing drugs preserve tissue structure and function in degenerating retina via phosphodiesterase inhibition, was published in theProceedings of the National Academy of Sciences.
In this study, we introduce a new class of therapeutics called Stress Resilience-Enhancing Drugs (SREDs) for the treatment of neurodegenerative conditions, specifically the worlds leading causes of blindness in age-related and inheritedretinal diseases, said Krzysztof Palczewski, Ph.D., Donald Bren Professor of Ophthalmology at the UCI School of Medicine and corresponding author on the study.
Through selective, pharmacological inhibition of cyclic nucleotide phosphodiesterases, our prototypical SREDs slowed or halted the development and progression of retinopathies in a number of genetic and environmental animal models.
Today, approximately 350 million people worldwide suffer from debilitating vision loss caused by either AMD or DR, and a large majority of these cases (>90%) have only minimally effective or notreatment optionsavailable. These chronic, progressive retinal diseases, including retinitis pigmentosa, arise from genetic and environmental disruptions of cellular and tissue stability.
Such disruptions accumulate with repeated exposures to stress over time, leading to progressive visual impairment and, in many cases, legal blindness.
Despite decades of research, therapeutic options for the millions of patients suffering from these disorders remain severely limited, especially for treating earlier stages of disease when the opportunity to preserve the retinal structure and visual function is greatest.
To address this urgent, unmet medical need, the researchers in this study innovated a systems pharmacology platform that leverages state-of-the-art disease modeling and characterization to identify novel, mechanism-based therapies that mitigate disease at the root cause.
The SRED therapeutic intervention enhanced resilience to acute and chronic forms of stress in the degenerating retina, thus preserving tissue structure and function across multiple models of age-related or inherited retinal disease.
Taken together, these findings exemplify a systems pharmacology approach todrug discoveryand development, revealing a new class of therapeutics with potential clinical utility in the treatment or prevention of the most common causes of blindness.
SREDs represent a promising strategy for patients and clinicians to combat disease in earlier stages with superior efficacy over the current standard of care, augmenting the arsenal of ophthalmic medications presently available in anti-angiogenics, corticosteroids, and nonsteroidal anti-inflammatory drugs (NSAIDs), said lead author Jennings Luu, MD/Ph.D. Doctoral Fellow of Pharmacology in the Medical Scientist Training Program at Case Western Reserve University and Visiting Scholar at University of California, Irvine.
Ultimately, it is our expectation that SREDs will someday serve as a standard of care for human aging, effectively providing patients the means to diminish suffering from debilitating ailments for which there currently exist no viabletherapeutic options, thereby extending human lifespan and healthspan irrespective of disease etiology.
Predicated in part on the discoveries highlighted in this publication, Luu and Palczewski have co-founded a seed-stage startup pharmaceutical company,Hyperion Therapeutics, Inc., which aims to commercialize theintellectual propertyassociated with their recent discoveries and introduce to the market new therapeutic agents for the treatment or prevention of AMD, DR, RP, and other progressive, incurable blinding diseases.
The Company was recently awarded first place in the Morganthaler-Pavey Startup Competition hosted by the Veale Institute for Entrepreneurship and has additionally partnered with UCI Beall Applied Innovation in the Wayfinder Incubator Program; through this strategic alliance, Luu and Palczewski are serving as co-investigators on a newly awarded Proof of Product grant, which will support the advancement of their pipeline therapies toward clinical trials and eventual commercialization.
Author: Press OfficeSource: UC IrvineContact: Press Office UC IrvineImage: The image is credited to Neuroscience News
Original Research: Closed access.Stress resilience-enhancing drugs preserve tissue structure and function in degenerating retina via phosphodiesterase inhibition by Jennings C. Luu et al. PNAS
Abstract
Stress resilience-enhancing drugs preserve tissue structure and function in degenerating retina via phosphodiesterase inhibition
Chronic, progressive retinal diseases, such as age-related macular degeneration (AMD), diabetic retinopathy, and retinitis pigmentosa, arise from genetic and environmental perturbations of cellular and tissue homeostasis. These disruptions accumulate with repeated exposures to stress over time, leading to progressive visual impairment and, in many cases, legal blindness.
Despite decades of research, therapeutic options for the millions of patients suffering from these disorders remain severely limited, especially for treating earlier stages of pathogenesis when the opportunity to preserve the retinal structure and visual function is greatest.
To address this urgent, unmet medical need, we employed a systems pharmacology platform for therapeutic development. Through integrative single-cell transcriptomics, proteomics, and phosphoproteomics, we identified universal molecular mechanisms across distinct models of age-related and inherited retinal degenerations, characterized by impaired physiological resilience to stress.
Here, we report that selective, targeted pharmacological inhibition of cyclic nucleotide phosphodiesterases (PDEs), which serve as critical regulatory nodes that modulate intracellular second messenger signaling pathways, stabilized the transcriptome, proteome, and phosphoproteome through downstream activation of protective mechanisms coupled with synergistic inhibition of degenerative processes.
This therapeutic intervention enhanced resilience to acute and chronic forms of stress in the degenerating retina, thus preserving tissue structure and function across various models of age-related and inherited retinal disease.
Taken together, these findings exemplify a systems pharmacology approach to drug discovery and development, revealing a new class of therapeutics with potential clinical utility in the treatment or prevention of the most common causes of blindness.
Here is the original post:
Eye-Opening Drug Discovery May Help Treat Age-Related Macular ... - Neuroscience News
- Neuroscience helps explain the teenage brain and mental health - ABC News - September 15th, 2024 [September 15th, 2024]
- XX Marks the Spot: Addressing Sex Bias in Neuroscience - The Scientist - September 15th, 2024 [September 15th, 2024]
- Neuroscience-based tools for transformative leadership - Fast Company - September 15th, 2024 [September 15th, 2024]
- How 100 Years of EEG Have Transformed Neuroscience - Being Patient - September 15th, 2024 [September 15th, 2024]
- Reconstructing dopamines link to reward - The Transmitter: Neuroscience News and Perspectives - September 15th, 2024 [September 15th, 2024]
- The neuroscience of itch in relation to transdiagnostic psychological approaches - Nature.com - September 15th, 2024 [September 15th, 2024]
- A README for open neuroscience - The Transmitter: Neuroscience News and Perspectives - September 15th, 2024 [September 15th, 2024]
- Dopamine and the need for alternative theories - The Transmitter: Neuroscience News and Perspectives - September 15th, 2024 [September 15th, 2024]
- Kim Stachenfeld on the dance between neuroscience and artificial intelligence - The Transmitter: Neuroscience News and Perspectives - September 15th, 2024 [September 15th, 2024]
- Vijay Mohan K. Namboodiri - The Transmitter: Neuroscience News and Perspectives - September 15th, 2024 [September 15th, 2024]
- Varied Cognitive Training Boosts Learning and Memory - Neuroscience News - September 15th, 2024 [September 15th, 2024]
- Issue | September 2024 | XX Marks the Spot: Addressing Sex Bias in Neuroscience - The Scientist - September 15th, 2024 [September 15th, 2024]
- The Transmitter Partners With World Wide Neuro and Brain Inspired, Building on Mission to Inform, Connect Neuroscience Community - StreetInsider.com - September 15th, 2024 [September 15th, 2024]
- Gene Therapy Offers Hope for Glaucoma and AMD - Neuroscience News - September 15th, 2024 [September 15th, 2024]
- The Neuroscience of Phantom Sensations: Can We Feel Whats Not Really There? - SciTechDaily - September 2nd, 2024 [September 2nd, 2024]
- Tau May Protect Brain Cells from Oxidative Damage - Neuroscience News - September 2nd, 2024 [September 2nd, 2024]
- Scientists use fainting to uncover new insights into the neuroscience of consciousness - PsyPost - September 2nd, 2024 [September 2nd, 2024]
- Biosensors and being fearless with Lin Tian - The Transmitter: Neuroscience News and Perspectives - September 2nd, 2024 [September 2nd, 2024]
- Can Neuroscience Train Your Brain to Be Happier? This Startup Has an App for That - Inc. - September 2nd, 2024 [September 2nd, 2024]
- Neuroscience Surprise: Different Types of Love Light Up Different Parts of the Brain - SciTechDaily - September 2nd, 2024 [September 2nd, 2024]
- Second paper from lab of Nobel Prize winner to be retracted - The Transmitter: Neuroscience News and Perspectives - September 2nd, 2024 [September 2nd, 2024]
- How cognitive bias affects your draft strategy with neuroscience professor Dr. Renee Miller - Yahoo Sports - August 5th, 2024 [August 5th, 2024]
- This 3-step approach to performance reviews uses neuroscience to make them less awful - Fast Company - August 5th, 2024 [August 5th, 2024]
- Is it time to worry about brain chimeras? - The Transmitter: Neuroscience News and Perspectives - August 5th, 2024 [August 5th, 2024]
- Sharing brain images can foster new neuroscience discoveries - American Heart Association - July 26th, 2024 [July 26th, 2024]
- Latest News: Neuroscience Major Applies What Shes Learned in the Classroom and in the Lab - Muhlenberg College - July 26th, 2024 [July 26th, 2024]
- BioIVT to Highlight its Integral Role in Drug and Diagnostic Discovery and Development in addition to Neuroscience Research at Premier Life Science... - July 26th, 2024 [July 26th, 2024]
- Alto Neuroscience Receives Funding Award from Wellcome Trust to Accelerate Development of ALTO-100 in Bipolar Depression Leveraging Precision... - July 26th, 2024 [July 26th, 2024]
- Neuroscience Says 3 Simple Steps Can Turn Disappointment and Stress Into Success and Fulfillment (and Boost Your Emotional Intelligence) - Inc. - July 26th, 2024 [July 26th, 2024]
- Golf: neuroscience reveals the secrets of better putting new study - The Conversation - July 26th, 2024 [July 26th, 2024]
- The Neuroscience Behind Video: Why Video is the Most Effective Marketing Channel - StreamTV Insider - July 26th, 2024 [July 26th, 2024]
- Building an autism research registry: Q&A with Tony Charman - The Transmitter: Neuroscience News and Perspectives - July 26th, 2024 [July 26th, 2024]
- Adjusting Proteins Increases Ozempics Effectiveness - Neuroscience News - July 18th, 2024 [July 18th, 2024]
- Low-Calorie Diets Harm Athletes Performance and Health - Neuroscience News - July 18th, 2024 [July 18th, 2024]
- Reflective Thinking Boosts Teen Brain Resilience to Violence - Neuroscience News - July 18th, 2024 [July 18th, 2024]
- Neuroscience Says Olympians Like Simone Biles Use the Autopilot Trick to Achieve Peak Performance. So Can You - Inc. - July 18th, 2024 [July 18th, 2024]
- What well-being is (and isnt), according to neuroscience - Big Think - July 18th, 2024 [July 18th, 2024]
- Brain Areas Take Micro-Naps While the Rest Stays Awake - Neuroscience News - July 18th, 2024 [July 18th, 2024]
- Persistent protein pairing enables memories to last - The Transmitter: Neuroscience News and Perspectives - July 18th, 2024 [July 18th, 2024]
- AI Enhances Story Creativity but Risks Reducing Novelty - Neuroscience News - July 18th, 2024 [July 18th, 2024]
- Infection Brain Inflammation Triggers Muscle Weakness - Neuroscience News - July 18th, 2024 [July 18th, 2024]
- Alto Neuroscience, Inc. (NYSE:ANRO) Receives Average Rating of Buy from Analysts - Defense World - July 18th, 2024 [July 18th, 2024]
- 2024 Kavli Prize awarded for research on face-selective brain areas - The Transmitter: Neuroscience News and Perspectives - June 18th, 2024 [June 18th, 2024]
- Unlocking Flow: The Neuroscience of Creative Bliss - Neuroscience News - April 15th, 2024 [April 15th, 2024]
- Revolutionizing Glioblastoma Treatment - Neuroscience News - April 15th, 2024 [April 15th, 2024]
- Decoding spontaneous thoughts from the brain via machine learning - EurekAlert - April 15th, 2024 [April 15th, 2024]
- Reducing Toxic AI Responses - Neuroscience News - April 15th, 2024 [April 15th, 2024]
- Advancing the neuroscience of human pregnancy - Nature.com - April 15th, 2024 [April 15th, 2024]
- Angela Bryan Awarded Hazel Barnes Prize | Psychology and Neuroscience - University of Colorado Boulder - April 15th, 2024 [April 15th, 2024]
- How Old Are You in Your Head? The Neuroscience of Subjective Age Reveals How to Stay Mentally Young - Inc. - April 15th, 2024 [April 15th, 2024]
- Biohaven Showcases Innovative Neuroscience Portfolio with 20 Presentations at the 2024 American Academy of ... - PR Newswire - April 15th, 2024 [April 15th, 2024]
- Those Who Use Willpower Deemed More Trustworthy - Neuroscience News - April 15th, 2024 [April 15th, 2024]
- How Sex and Gender Shape Our Cognition - Neuroscience News - April 15th, 2024 [April 15th, 2024]
- War's Toll on the Brain: Widespread PTSD and Anxiety Among Ukrainians - Neuroscience News - April 15th, 2024 [April 15th, 2024]
- Paints and Pesticides Linked to ALS Risk - Neuroscience News - April 15th, 2024 [April 15th, 2024]
- AI STORIES: A New Vision for AI and Narratives - Neuroscience News - April 15th, 2024 [April 15th, 2024]
- Neuroscience Breakthrough Unveils How We Learn and Remember - SciTechDaily - April 15th, 2024 [April 15th, 2024]
- Pregnancy's Toll: Accelerated Aging in Young Mothers - Neuroscience News - April 15th, 2024 [April 15th, 2024]
- Learning and Memory Formation's Molecular Basis - Neuroscience News - April 15th, 2024 [April 15th, 2024]
- Acetaminophen in Pregnancy Not Linked to Autism, ADHD Risk - Neuroscience News - April 15th, 2024 [April 15th, 2024]
- Childhood Loneliness Linked to Later Psychosis - Neuroscience News - April 15th, 2024 [April 15th, 2024]
- Vigil Neuroscience, Inc. (NASDAQ:VIGL) Expected to Post Q1 2024 Earnings of ($0.58) Per Share - Defense World - March 29th, 2024 [March 29th, 2024]
- International Brain Research Organisation (IBRO) Diversity Grants 2024 Opportunity Desk - Opportunity Desk - March 29th, 2024 [March 29th, 2024]
- Hereditary Alzheimer's Transmitted Via Bone Marrow Transplants - Neuroscience News - March 29th, 2024 [March 29th, 2024]
- Household Chemicals Linked to Brain Health Risks - Neuroscience News - March 29th, 2024 [March 29th, 2024]
- Cheers to Longevity: Couples Who Drink Together, Live Longer - Neuroscience News - March 29th, 2024 [March 29th, 2024]
- Sleeplessness Makes You Feel Up To Ten Years Older - Neuroscience News - March 29th, 2024 [March 29th, 2024]
- Aging Brain Cells Have Prolonged Death Process - Neuroscience News - March 29th, 2024 [March 29th, 2024]
- Anxiety Drives Wishful Thinking to Risky Levels - Neuroscience News - March 29th, 2024 [March 29th, 2024]
- Prolonged Progestogen Use Linked to Brain Tumor Risk - Neuroscience News - March 29th, 2024 [March 29th, 2024]
- The Genetic Secrets of Neuron Formation - Neuroscience News - March 29th, 2024 [March 29th, 2024]
- Vigil Neuroscience Reports Fourth Quarter and Full Year 2023 Financial Results and Provides Business Update - Yahoo Finance - March 29th, 2024 [March 29th, 2024]
- Big research, little time: Medical neuroscience student wins 3 Minute Thesis finals - Dal News - March 29th, 2024 [March 29th, 2024]
- The new NeuroAI - Nature.com - March 29th, 2024 [March 29th, 2024]
- Exploring Aphantasia: The Mind Without a Mental Picture - Neuroscience News - March 29th, 2024 [March 29th, 2024]
- Altered Brain pH Linked to Cognitive Disorders - Neuroscience News - March 29th, 2024 [March 29th, 2024]
- Emotion vs. Reason: Rethinking Decision-Making - Neuroscience News - March 29th, 2024 [March 29th, 2024]
- DNA Damage and Inflammation Key to Memory Formation - Neuroscience News - March 29th, 2024 [March 29th, 2024]
- Embracing Neurodiversity: Beyond Stigma to Strength - Neuroscience News - March 29th, 2024 [March 29th, 2024]
- Devil in the Details: The Visual World of Prosopometamorphopsia - Neuroscience News - March 29th, 2024 [March 29th, 2024]