New small-molecule drugs show potential clinical benefit in treating the world’s leading causes of blindness

In a UCLA study, led by Irvine, researchers have discovered small molecule drugs with potential clinical benefit in treating celiac disease Age-related macular degeneration (AMD), diabetic retinopathy (DR), and retinitis pigmentosa (RP).

The study entitled “Stress resilience-enhancing drugs preserve tissue structure and function in retinal degeneration by inhibiting phosphodiesterase.“in Proceedings of the National Academy of Sciences.

In this study, we introduce a new class of therapies called Stress-enhancing drugs (SREDs) For the treatment of neurodegenerative conditions, specifically the major global causes of blindness in age-related and inherited retinal diseases. Through selective pharmacological inhibition of cyclic nucleotide phosphodiesterase, our SRED model devices have slowed or halted the progression and progression of retinopathies in a number of genetic and environmental animal models.”

Krzysztof Palczewski, MD, Donald Brin Professor of Ophthalmology at UCI School of Medicine and corresponding author on the study.

Today, approximately 350 million people worldwide suffer from visual impairment caused by either AMD or DR, and the vast majority of these cases (>90%) have little or no effective treatment options. Chronic and advanced retinal diseases, including retinitis pigmentosa, arise from genetic and environmental disturbances of cell and tissue stability. These disorders accumulate with repeated exposure to stress over time, leading to progressive visual impairment and, in many cases, to legal blindness. Despite decades of research, treatment options for the millions of patients with these disorders are still very limited, especially for treating the early stages of the disease when the chance of preserving retinal structure and visual function is greatest.

To address this urgent unmet medical need, the researchers in this study devised a basic systems pharmacology platform that takes advantage of the latest disease models and characterization to identify novel therapies based on mechanisms that alleviate disease at the root cause. The SRED therapeutic intervention enhanced resilience to both acute and chronic forms of stress in the degenerating retina, thereby preserving tissue structure and function across multiple age-related or inherited models of retinal disease. Taken together, these findings model a systemic pharmacology approach to drug discovery and development, and reveal a new class of therapies with potential clinical utility in treating or preventing the most common causes of blindness.

“SRED devices represent a promising strategy for patients and clinicians to control the disease in the early stages at the highest level effectiveness Increasing the arsenal of ophthalmic drugs currently available in antiangiogenic drugs, corticosteroids, and non-steroidal anti-inflammatory drugs,” said lead author Jennings Lu, MD/PhD in Pharmacology in the Medical World training program at Case Western Reserve University and researcher Visitor at the University of California, Irvine.” Ultimately, we anticipate that SREDs will one day serve as the standard of care for human aging, effectively providing patients with the means to reduce suffering from debilitating diseases for which there are currently no viable treatment options, thereby extending life. human and the health period, regardless of the pathogens.

This study was funded in part by the National Institutes of Health, the United States Department of Veterans Affairs, and the International Center for Translational Eye Research and Prevention of Blindness Research.

Based in part on the discoveries highlighted in this post, Luu and Palczewski co-founded a seed-stage pharmaceutical startup, Hyperion Therapeutics, Inc. , which aims to commercialize the intellectual property associated with their recent discoveries and bring to market new therapeutic agents for the treatment or prevention of AMD, DR, RP, and other progressive and intractable blinding diseases. The company recently took first place in the Morganthaler-Pavey Startup Competition hosted by the Veale Institute for Entrepreneurship and has partnered with UCI Beall Applied Innovation in the Wayfinder Incubator Program; Through this strategic alliance, Luu and Palczewski are serving as co-investigators for a newly awarded Proof of Product grant, which will support the development of their pipeline therapies toward clinical trials and eventual commercialization.