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 Says Music Is an Emotion Regulation Machine. Heres What to Play for Happiness, Productivity, or Deep Thinking - Inc.com - April 19th, 2025 [April 19th, 2025]
- Early Maternal Affection Shapes Key Personality Traits for Life - Neuroscience News - April 19th, 2025 [April 19th, 2025]
- Elons new neuroscience major highlighted by Greensboro News & Record - Elon University - April 19th, 2025 [April 19th, 2025]
- Brain Blast event at St. Lawrence University teaches local students neuroscience - North Country Now - April 19th, 2025 [April 19th, 2025]
- AI Reveals What Keeps People Committed to Exercise - Neuroscience News - April 19th, 2025 [April 19th, 2025]
- The "Holy Grail" of Neuroscience? Researchers Create Stunningly Accurate Digital Twin of the Brain - The Debrief - April 19th, 2025 [April 19th, 2025]
- Annenberg School Vice Dean Emily Falk publishes book on the neuroscience of decision-making - The Daily Pennsylvanian - April 19th, 2025 [April 19th, 2025]
- Music-Induced Chills Trigger Natural Opioids in the Brain - Neuroscience News - April 19th, 2025 [April 19th, 2025]
- What We Value: The Neuroscience of Choice and Change - think.kera.org - April 19th, 2025 [April 19th, 2025]
- Kile takes top neuroscience post at Sutter Health as system pushes to align care, expand trials - The Business Journals - April 19th, 2025 [April 19th, 2025]
- A Grain of Brain, 523 Million Synapses, and the Most Complicated Neuroscience Experiment Ever Attempted - SciTechDaily - April 19th, 2025 [April 19th, 2025]
- Mild Brain Stimulation Alters Decision-Making Speed and Flexibility - Neuroscience News - April 19th, 2025 [April 19th, 2025]
- Cannabis studies were informing fundamental neuroscience in the 1970s - Nature - April 10th, 2025 [April 10th, 2025]
- To make a meaningful contribution to neuroscience, fMRI must break out of its silo - The Transmitter - April 10th, 2025 [April 10th, 2025]
- Steve Jobss Unexpected Secret to Being More Creative (Backed by Neuroscience) - Inc.com - April 10th, 2025 [April 10th, 2025]
- Challenging Decades of Neuroscience: Brain Cells Are More Plastic Than Previously Thought - SciTechDaily - April 10th, 2025 [April 10th, 2025]
- Q&A: Lundbecks head of R&D on letting biology speak in neuroscience - Endpoints News - April 10th, 2025 [April 10th, 2025]
- Why it's hard to study the neuroscience of psychedelics : Short Wave - NPR - April 10th, 2025 [April 10th, 2025]
- Fear Sync: How Males and Females Respond to Stress Together - Neuroscience News - April 10th, 2025 [April 10th, 2025]
- Chemotherapy Disrupts Brain Connectivity - Neuroscience News - April 10th, 2025 [April 10th, 2025]
- Newly awarded NIH grants for neuroscience lag 77 percent behind previous nine-year average - The Transmitter - April 10th, 2025 [April 10th, 2025]
- Wittstein interviewed by The Times News about new neuroscience major - Elon University - April 10th, 2025 [April 10th, 2025]
- Alto Neuroscience initiated with a Buy at H.C. Wainwright - Yahoo Finance - April 10th, 2025 [April 10th, 2025]
- New map of brain hailed as watershed for neuroscience - The Times - April 10th, 2025 [April 10th, 2025]
- GSK Ramps Up Neuroscience Investment With ABL Brain Shuttle Deal - insights.citeline.com - April 10th, 2025 [April 10th, 2025]
- ADHD and Music: Why Background Beats May Boost Study Focus - Neuroscience News - April 10th, 2025 [April 10th, 2025]
- Brains Rewire Themselves to Survive Deadly Infection - Neuroscience News - April 10th, 2025 [April 10th, 2025]
- AbbVie Hold Rating: Balancing Strong Immunology Growth with Challenges in Aesthetics, Neuroscience, and Oncology - TipRanks - April 10th, 2025 [April 10th, 2025]
- Want to Feel Better and Be More Mindful? Neuroscience Says This Habit Might Be Holding You Back - Inc.com - April 10th, 2025 [April 10th, 2025]
- How One Bad Meal Rewires the Brain to Avoid That Food Forever - Neuroscience News - April 10th, 2025 [April 10th, 2025]
- Marcus Neuroscience Institute to Host Brain and Spine Symposium - South Florida Hospital News - March 30th, 2025 [March 30th, 2025]
- Elon University to launch neuroscience major in fall 2025 - Today at Elon - March 30th, 2025 [March 30th, 2025]
- The brains stalwart sentinels express an unexpected gene - The Transmitter: Neuroscience News and Perspectives - March 30th, 2025 [March 30th, 2025]
- Video catches microglia in the act of synaptic pruning - The Transmitter: Neuroscience News and Perspectives - March 30th, 2025 [March 30th, 2025]
- Null and Noteworthy: Reexamining registered reports - The Transmitter: Neuroscience News and Perspectives - March 30th, 2025 [March 30th, 2025]
- Accepting the bitter lesson and embracing the brains complexity - The Transmitter: Neuroscience News and Perspectives - March 30th, 2025 [March 30th, 2025]
- NIH neurodevelopmental assessment system now available as iPad app - The Transmitter: Neuroscience News and Perspectives - March 30th, 2025 [March 30th, 2025]
- Stronger Bonds Before Birth Shape Healthier Mother-Child Futures - Neuroscience News - March 30th, 2025 [March 30th, 2025]
- How Emotionally Intelligent People Learn to Control Their Inner Voice, Backed by Neuroscience - Inc. - March 30th, 2025 [March 30th, 2025]
- Gabriele Scheler reflects on the interplay between language, thought and AI - The Transmitter: Neuroscience News and Perspectives - March 30th, 2025 [March 30th, 2025]
- Worlds first crowd-sourced neuroscience study aims to understand how our brains predict the future - EurekAlert - March 15th, 2025 [March 15th, 2025]
- Rewriting Neuroscience: Possible Foundations of Human Intelligence Observed for the First Time - SciTechDaily - March 15th, 2025 [March 15th, 2025]
- Calculating neurosciences carbon cost: Q&A with Stefan Pulver and William Smith - The Transmitter: Neuroscience News and Perspectives - March 15th, 2025 [March 15th, 2025]
- The future of neuroscience research at U.S. minority-serving institutions is in danger - The Transmitter: Neuroscience News and Perspectives - March 15th, 2025 [March 15th, 2025]
- Dopamine and social media: Why you cant stop scrolling, according to neuroscience - PsyPost - March 15th, 2025 [March 15th, 2025]
- Neuroscience Discovered a Clever Trick for Squeezing More Joy Out of Everyday Pleasures - Inc. - March 15th, 2025 [March 15th, 2025]
- The limits of neuroscience - The Transmitter: Neuroscience News and Perspectives - March 15th, 2025 [March 15th, 2025]
- BPOM Explains The Benefits Of Fasting From The Health And Neuroscience Side - VOI English - March 15th, 2025 [March 15th, 2025]
- How tiny tardigrades could help tackle systems neuroscience questions - The Transmitter: Neuroscience News and Perspectives - March 15th, 2025 [March 15th, 2025]
- Alison Preston explains how our brains form mental frameworks for interpreting the world - The Transmitter: Neuroscience News and Perspectives - March 15th, 2025 [March 15th, 2025]
- The Mystical Mind Meets Neuroscience: Seeking the Roots of Consciousness - Next Big Idea Club Magazine - March 15th, 2025 [March 15th, 2025]
- Myosin Therapeutics Closes Second Seed Round to Advance Clinical Trials for Innovative Cancer and Neuroscience Therapies - PR Newswire - March 5th, 2025 [March 5th, 2025]
- Neuroscience Ph.D. programs adjust admissions in response to U.S. funding uncertainty - The Transmitter: Neuroscience News and Perspectives - March 5th, 2025 [March 5th, 2025]
- New tools help make neuroimaging accessible to more researchers - The Transmitter: Neuroscience News and Perspectives - March 5th, 2025 [March 5th, 2025]
- Future Thinking Training Reduces Impulsivity - Neuroscience News - March 5th, 2025 [March 5th, 2025]
- Null and Noteworthy, relaunched: Probing a schizophrenia biomarker - The Transmitter: Neuroscience News and Perspectives - March 5th, 2025 [March 5th, 2025]
- How to communicate the value of curiosity-driven research - The Transmitter: Neuroscience News and Perspectives - March 5th, 2025 [March 5th, 2025]
- Cognitive neuroscience approach to explore the impact of wind turbine noise on various mental functions - Nature.com - March 5th, 2025 [March 5th, 2025]
- Football on the Brain: Helping coaches embed neuroscience knowledge - Training Ground Guru - March 5th, 2025 [March 5th, 2025]
- Taking Control: Using Neuroscience to Build Better Lives - theLoop - March 5th, 2025 [March 5th, 2025]
- Creating a pipeline of talent to feed the growth of Neuroscience: Lessons from Ghana - Myjoyonline - March 5th, 2025 [March 5th, 2025]
- Exclusive: NIH appears to archive policy requiring female animals in studies - The Transmitter: Neuroscience News and Perspectives - February 25th, 2025 [February 25th, 2025]
- Roll On Down The Highway 2025 Tour coming to Neuroscience Group Field - WeAreGreenBay.com - February 25th, 2025 [February 25th, 2025]
- STEM organizations host Neuroscience Outreach Fair for local K-12 students - University of Virginia The Cavalier Daily - February 25th, 2025 [February 25th, 2025]
- Adapt or die: Safeguarding the future of diversity and inclusion funding in neuroscience - The Transmitter: Neuroscience News and Perspectives - February 25th, 2025 [February 25th, 2025]
- The last two-author neuroscience paper? - The Transmitter: Neuroscience News and Perspectives - February 25th, 2025 [February 25th, 2025]
- Gate Neurosciences Strengthens Focus on the Synapse as a Therapeutic Target with Acquisition of Boost Neuroscience - Business Wire - February 25th, 2025 [February 25th, 2025]
- Why Firefly Neuroscience, Inc. (AIFF) Is Soaring This Year So Far - Yahoo Finance - February 25th, 2025 [February 25th, 2025]
- Breaking the barrier between theorists and experimentalists - The Transmitter: Neuroscience News and Perspectives - February 25th, 2025 [February 25th, 2025]
- Preserving Brain Health and Advancing Neuroscience - University of Miami - February 25th, 2025 [February 25th, 2025]
- Science must step away from nationally managed infrastructure - The Transmitter: Neuroscience News and Perspectives - February 25th, 2025 [February 25th, 2025]
- Repurposed Blood Pressure Drug May Treat ADHD - Neuroscience News - February 25th, 2025 [February 25th, 2025]
- How to teach students about science funding - The Transmitter: Neuroscience News and Perspectives - February 25th, 2025 [February 25th, 2025]
- Reflecting on 2024: Advancing Neuroscience Research to Improve Neurological Health - National Institute of Neurological Disorders and Stroke - February 25th, 2025 [February 25th, 2025]
- Brains Hidden Circuitry for Risk and Reward Uncovered - Neuroscience News - February 25th, 2025 [February 25th, 2025]
- Why We Keep Exploring Even After Learning the Best Strategy - Neuroscience News - February 25th, 2025 [February 25th, 2025]
- Unlocking Cellular Youth: The Protein That Reverses Aging - Neuroscience News - February 25th, 2025 [February 25th, 2025]
- This paper changed my Life: Bill Newsome reflects on a quadrilogy of classic visual perception studies - The Transmitter: Neuroscience News and... - February 25th, 2025 [February 25th, 2025]
- Roundup: The false association between vaccines and autism - The Transmitter: Neuroscience News and Perspectives - February 3rd, 2025 [February 3rd, 2025]
- Static pay, shrinking prospects fuel neuroscience postdoc decline - The Transmitter: Neuroscience News and Perspectives - February 3rd, 2025 [February 3rd, 2025]