Researcher Pioneers Faster, Cheaper Gene Therapy for Hemoglobin Disorders

For millions living with hemoglobin deficiencies such as sickle cell disease or beta thalassemia, every day is a battle against pain, costly treatments, and uncertainty. Dr. Frank Park is racing to help.

A new gene therapy being developed at the University of Tennessee Health Science Center could provide a more accessible cure. Frank Park, PhD, a researcher at UT Health Sciences' College of Pharmacy, believes he's on the verge of a more efficient and affordable solution that could revolutionize how we combat hemoglobin deficiencies through his gene therapy, nicknamed "Minirolu."

"My main goal isn't to make money," Dr. Park said. "I've been working on this for almost a year for free, because of my background in vector biology and genome manipulation."

Unlike existing gene therapy methods for treating hemoglobin deficiencies, which are costly and require lengthy hospital stays as well as multiple blood draws, Minirolu aims to deliver results efficiently at the point of care, enabling faster, more accessible, life-saving treatment.

"There are always going to be issues where if you are not first to market," Dr. Park said. "You can't come out with an equally effective product. You must deliver something that's considerably better. Is that possible? I think we can. I believe we have something."

Dr. Park's contributions to drug discovery and development are a vital part of the College of Pharmacy's reputation for research excellence, and contribute to the university's R1 status among the nation's top research institutions. Since 2020, the college has consistently ranked among the top 15 institutions funded by the National Institutes of Health (NIH) among colleges of pharmacy, reaching as high as No. 6 in 2022.

Current Hemoglobin Deficiency Treatments and A Hope for A Cure

Hemoglobin deficiencies affect how red blood cells carry oxygen. These inherited conditions impact thousands in the U.S. and millions globally, often requiring repeated transfusions and lifelong treatment and medication. In the U.S., sickle cell disease is the most encountered version, affecting about 100,000 Americans, mostly African Americans, while beta thalassemia is more common in Europe. Gene therapy offers hope for a cure to these diseases.

"What we're doing is taking a replication-defective viral vector from Lentiviruses," Dr. Park said. "We strip it down to just the virus shell and add an expression cassette, including gene components to overexpress beta-globin. Essentially, the goal is to replace the faulty variant with a functional wild-type protein, enabling individuals with this disease to function normally."

The treatment begins by collecting the patient's own blood-forming cells, which are sent to a specialized laboratory where they are modified using a viral vector system, so they can begin to produce normal hemoglobin. Before the genetically modified cells can be transfused back into the same patient, they must go through multiple rounds of testing to ensure they're safe and functioning as intended. These steps and others involving the patients, and higher costs per patient, can take several months or longer to complete. Dr. Park and his group are looking to shorten this timeline in order to treat patients more efficiently.

How Minirolu Lowers Costs and Improves Efficiency

"It's not only that the cost is lower, but it's also more efficient," Dr. Park said of Minirolu. "With other companies, you may need to perform multiple blood isolations, two, three, or even four, and it could take up to a year before patients can receive treatment. So, we can get in there if it's just as effective, but if its cost is cheaper and we can get it timelier, I mean, we're really looking sweet then."

Dr. Park and his investor, Patrick Girondi, president and founder of San Rocco Therapeutics, whose son has beta-thalassemia, aim to challenge the lengthy, costly process by developing a point-of-care system within the hospital. They're currently collaborating with a hospital in Bambino Gesù, Italy, where experienced clinicians will handle cell isolation, vector addition, and testing. This approach seeks to streamline treatment, reduce time and expenses, and enable earlier patient care.

"I believe our technological advances are now ready to move forward," Dr. Park said. "I made some tweaks to optimize our vector, we customized it slightly, tested various versions, and found one that's about 50% better at producing more of the needed protein, which reduces costs. This is important because increasing protein production addresses a key concern from the FDA about manufacturing capacity. Our improvements should lead to a safer and more effective drug, even though we're not the first to market. Compared to other companies' current vectors, ours should be better and cheaper, with fewer serious side effects."

Future Steps for Minirolu

The team has already developed a Good Manufacturing Practice-compliant vector, a type of gene delivery vehicle such as a viral vector, designed to meet rigorous regulatory standards. This ensures the vector is consistently produced at the highest quality, suitable for human clinical trials and commercial use.

Additionally, they have secured over a million dollars in self-funding. Currently, they're developing sterile, safe cell products for patient infusion, with regulatory submissions underway in Europe (Italy) and collaborations in the U.S., including NIH. Their goal is to finalize their process within four to six months and commence a phase 1/2 clinical trial in 2026. Beyond beta thalassemia, this innovation shows potential for sickle cell disease and other hemoglobinopathies, offering new hope to millions affected by these conditions.