How a farsighted initiative is powering revolutionary science

Cancer treatment can be something of a trade-off for a patient. Radiation therapy, for example, is effective at killing or slowing the growth of cancer cells; however, the damage to nearby healthy cells can cause gruelling side effects, including fatigue, nausea and hair loss. Challenging for any patient with cancer, these side effects are a particularly heavy burden for a child.

Researchers at Cincinnati Children’s hope they have found a solution through an investigational ultra-high-dose-rate proton therapy that can be administered in less than one second, significantly reducing exposure to healthy cells. The team, in the Cincinnati Children’s and University of Cincinnati’s Proton Therapy Center, is conducting the world’s first clinical trial of FLASH, which is showing promise in maintaining treatment efficacy while reducing side effects. John Perentesis, physician and research director of the Proton Therapy Center and director of oncology and cancer programmes at Cincinnati Children’s, says, “Our goal is to establish a foundation for future potential trials in brain tumours, sarcomas, lymphomas, lung cancer and other malignancies, and we are excited about the impact this research might have on cancer care.”

The cutting-edge radiation treatment available at the Proton Therapy Center is a major reason the Cincinnati Children’s was ranked as the Best Children’s Hospital in 2023-2024 by the US News & World Report. And it’s not Ohio’s only entry in that list. Just over 100 miles north is sixth-ranked Nationwide Children’s Hospital in Columbus. The state also boasts the Cleveland Clinic, ranked by Newsweek as the second-best general hospital in the world, and the highly regarded University Hospitals Rainbow Babies & Children’s. This clinical expertise is paired with a thriving university system: attracting nearly $1 billion in funding from the National Institutes of Health and creating more than 11,000 life science graduates each year.

However, according to JobsOhio, the state’s private economic development corporation, the life science story is just getting started. In 2020 and 2021, as many US states were pulling away from innovation funding during the pandemic, the State of Ohio began investing. JobsOhio made a $300 million commitment to further grow life-science research, commercialization, talent and real estate.

As part of the investment, JobsOhio has facilitated the creation of three Innovation Districts in Cleveland, Columbus and Cincinnati. As well as the paediatric institutions already mentioned, the initiative includes The Ohio State University, Case Western Reserve University, the University of Cincinnati, and MetroHealth Medical Center in Cleveland. The aim is to translate the investment into more than 60,000 new jobs, 40,000 new STEM graduates, and $20 billion of research spend over the coming decade.

Innovation with a clinical focus

The impact of the support is already being felt. The Cleveland Innovation District played a key role in enabling a cutting-edge sickle-cell trial at Cleveland’s University Hospitals. Led by John Letterio, division chief of paediatric haematology and oncology, the trial uses gene-editing technology (CRISPR/Cas12) to permanently correct the genetic mutation responsible for sickle-cell disease. The early results are encouraging. “The very first patient who received this life-changing therapy has just gone home,” says Letterio. “He walked into the hospital with sickle-cell disease and, for all practical purposes, he left without it.” The investment from JobsOhio enabled Letterio to add the talent and the personnel necessary to execute and deliver the gene therapy, he adds.

Growth is key. Ohio is relatively new to the life sciences scene, compared to the more established research hubs around Boston and San Francisco, and its institutions are aggressively recruiting principal investigators, hunting federal funding, and building statewide consortiums.

Serpil Erzurum, chief research and academic officer at the Cleveland Clinic, says her institution has been rapidly growing its research enterprise, which reached an all-time high of US$402 million in 2023, around 23% higher than in 2021. Its Center for Immunotherapy and Precision Immuno-Oncology, which was established in 2020, is advancing the development of novel anti-tumour vaccines as well as chimeric antigen receptor (CAR) T cell therapies, in which a patient’s own immune cells are engineered to recognize and destroy tumours¹.

At Columbus-based Nationwide Children’s Hospital, researchers have played a foundational role in developing FDA-approved treatments for life-threatening congenital disorders including Duchenne Muscular Dystrophy — a progressive, degenerative disease that until recently meant disability and an early death for patients. In June 2023, Sarepta Therapeutics, a Cambridge, Massachusetts based biotechnology company with a significant R&D team in Columbus, received FDA approval for the first gene therapy to treat Duchenne Muscular Dystrophy. Based on technology developed at Nationwide by paediatric neurologist and principal investigator Jerry Mendell, the technology addresses the root cause of Duchenne – mutations in the dystrophin gene.

Nationwide Children’s has built a reputation for treating children with rare diseases — conditions diagnosed in fewer than 200,000 people in the United States, although these various disorders collectively affect up to 30 million Americans. “We attract families from all over — from all 50 states, as well as 40 different countries this past year,” says Cynthia Gerhardt, Nationwide Children’s chief clinical research officer. As a psychologist, she also praises her hospital’s extensive facilities for studying and treating mental health and behavioural disorders in youths. In 2020, the hospital opened its Big Lots Behavioral Health Pavilion, which is the largest paediatric centre of its kind in the United States. “Most mental health disorders will develop in the teenage and early adulthood years, so it's important to get those kids and families help early,” says Gerhardt.

On the regenerative medicine front, the Center for Stem Cell and Organoid Medicine (CuSTOM), at Cincinnati Children’s, has assembled world-renowned experts in organoids: three-dimensional assemblies of cultured cells that can be used to model, and potentially repair, human organs. “They’ve done it with the gut, and they’re working on the liver, neural cells, stomach — many different organs,” says Tina Cheng, chief medical officer at Cincinnati Children’s. She adds that CuSTOM director, Michael Helmrath, hopes to begin clinical testing of an organoid-based strategy for repairing congenital intestinal defects in paediatric patients soon.

Investing in the future

The influx of state, federal and private sector funding is helping to attract expertise and commercial partners to explore new and emerging medical technologies. In the Cleveland Innovation District, Azenta Life Sciences is creating a biobank — a repository of patient samples that researchers can use to better understand the molecular and genetic features of a wide range of diseases. In another recent partnership, Cleveland Clinic welcomed IBM’s Quantum System One, the first quantum computer dedicated to healthcare research, to its campus. The installation is part of a 10-year Discovery Accelerator Partnership intended to quicken the pace of solving big challenges in biomedical research.

Building a homegrown biotech and pharma industry is also a priority. Several hospitals have spawned successful start-ups, which can be invaluable for creating a critical mass that attracts even more talent and entrepreneurship. Nationwide Children’s has spun off 18 Columbus-based companies in recent years, including gene-therapy manufacturing specialists Andelyn Biosciences. With support from JobsOhio, Andelyn Biosciences opened a new manufacturing facility in June 2023, dedicated to producing the precisely engineered viral particles needed to deliver gene therapies to patients. This company has experienced rapid growth in the past three years as more of its gene therapies enter the clinic, and the new Columbus facility will triple Andelyn’s production capacity.

The final component of the Innovation District project is ensuring that there is a growing corpus of young talent. “By bringing together world-class medical and research facilities, academic institutions, and private corporations, Ohio is creating a sustainable ecosystem of innovation and talent,” says J.P. Nauseef, JobsOhio’s president and CEO. “Our Innovation District initiative invests in the talent and infrastructure critical to propelling the next generation of discovery within our paediatric centres of excellence.”

All three Innovation Districts include major universities, and JobsOhio projects that their investments will ultimately result in 40,000 additional college graduates with degrees that prepare them for STEM careers. But this training must also evolve to meet the needs of a rapidly evolving scientific and medical landscape. “We need to be very agile and adept at understanding and projecting what knowledge gaps will need filling 5 to 10 years from now,” says Gerhardt.

Considerable work remains to be done, but Erzurum is optimistic about the future of Cleveland and its sister cities, and believes that this ongoing infusion of investment and strategic planning can turn Ohio’s clinical research community into a shining example for others. “We're planting seeds,” she says. “What I would hope for — and I see it happening as we plant these seeds and companies come — is that the heartland in general becomes an opportunity for all of America to see how we can work together.”