Development of Aromatic Aldehydes for the Treatment of Sickle Cell Disease

Authors

Albert Opare, Virginia Commonwealth University

Original Publication Date

2025

Document Type

Presentation

Comments

11th Annual VCU 3MT® Competition, held on October 3, 2025.

Abstract

Sickle cell disease (SCD) is a genetic disorder that causes red blood cells to become rigid and sickle-shaped, blocking blood flow and leading to severe pain, organ damage, and shortened life expectancy. Current treatments are often toxic, costly, or only partially effective. Albert Opare's research aims to develop aromatic aldehydes as affordable, functional cures for SCD. These small molecules bind directly to hemoglobin, preventing red blood cells from sickling and reducing the complications of the disease. Specifically, Albert is synthesizing amide analogs of our clinical lead compound, ILX-002, to improve potency and stability.

Transcription

Next, we have Albert Opare, Development of Aromatic Aldehydes for the Treatment of Sickle Cell Disease. They're in the School of Pharmacy, and their advisor is Dr. Yan Zhang. Picture this. Imagine being stabbed multiple times all over your body whilst having a migraine. Or imagine having multiple fractures and broken bones and glass flowing through your body. I'm not here to scare you, but you see, these are some of the ways that some patients with sickle cell disease describe the excruciating pain associated with vaso-occlusive crisis. And this pain can persist for days and weeks without end, rendering them helpless and weak. Sickle cell disease in itself is a genetic disease that causes the red blood cells, which are normally flexible and free-flowing, to become rigid and adopt a characteristic sickle shape. Once sickled, these red blood cells polymerize together, blocking blood vessels and even destroying them. This leads to a series of complications such as inflammation, vaso-occlusive crisis, multiple organ damage, and premature death. In the U.S., over 100,000 people are affected by this disease, with more than 8 million people being affected globally. The disheartening thing is patients with sickle cell disease have a reduced life expectancy of 20 to 30 years, less than the expected average. Currently, most drugs approved for the treatment of the disease are either too toxic, less efficacious, or too expensive with gene therapies going for two to three million dollars per person. So obviously there's a need for a drug that is more efficacious, less toxic, and more affordable. And this is where I come in. My research therefore involves developing compounds known as aromatic aldehydes as functional cure for sickle cell disease. These compounds work by binding directly to hemoglobin preventing the red blood cells from sickling and also destabilizing the polymer hence preventing the negative complications i mentioned previously specifically i am developing amide analogs of our clinical lead ilx002 and this these amide analogs were developed to be superior in terms of potency and stability currently 65 of these compounds have been synthesized and preliminary studies show that some of these compounds potentially inhibits red blood cell sickling interestingly these compounds also were stable in these cells even after 48 hours additionally none of these compounds tested showed any significant toxicity to the red blood cells based on these results we will be synthesized we will be testing the most potent compounds in animal models where we hope to select a lead for future preclinical studies. It is worth knowing that being small molecules, our compounds will be more affordable than some current therapies, including gene therapy, whilst addressing issues of efficacy and toxicity. Ultimately, our goal is to develop a drug that makes it to the clinic to treat sickle cell disease, eventually becoming a beacon of hope for these patients and creating a world where they are no longer weak, but strong. Thank you.

Rights

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