Targeting medicine-engineering to “orphan diseases”
Clinical pharmacologist Harry Shirkey noted more than 50 years ago that children are often “therapeutic orphans” in biomedical research. Today, we see a continued five- to 10-year lag of pediatric biomedical advances behind the adult populations.
In pediatric healthcare, approximately 90% of healthcare resources are utilized by 5 to 10% of children who suffer complex and chronic medical conditions. In many cases, these 5,000 pediatric-only rare conditions, or “orphan diseases,” lack a market large enough to drive intervention, which permeates both the pharmaceutical and biomedical device industries.
More than 80% of biomedical devices approved by the Food and Drug Administration (FDA) do not have testing or indication for use in children under 18 years old. To support device development and adaptation for pediatric use, the FDA provides humanitarian use devices (HUD) exemptions for target groups of less than 8,000 individuals per year — and there are encouraging examples. Indiana-based Cook Medical has a long history of pediatric medical device development, starting with the Harrison Fetal Bladder Stent Set in 1997, the first humanitarian use device approved in the U.S. However, 25 years later, there are just 79 approved devices and only a small fraction of them are for pediatric use.
American universities have an opportunity to serve as a development force to conduct research in therapeutics and biomedical technologies for children and adolescents. Our academic institutions can approach this in in two ways: Carrying out fundamental, federally funded research on these orphan diseases; and partnering with biomedical device companies to scale, modify, test and deploy lifesaving pediatric technologies.
For example, Purdue University and Indiana University are forming a strong Engineering-Medicine partnership. The Weldon School of Biomedical Engineering at Purdue University, Indiana University School of Medicine’s Department of Pediatrics and the renowned Riley Hospital for Children in Indianapolis created an interdisciplinary nexus for addressing the longstanding lag in pediatric diagnostic devices, technologies and therapeutics. This research includes the development of wearable sensors for continuous monitoring and point-of-care diagnostics; imaging technology and data processing advancements; neuro-engineering; and micro- and nano-devices to monitor metabolic diseases and pharmaceutical delivery to children.
Take Duchenne Muscular Dystrophy, for instance, which is a pediatric cardiovascular disease that results in a progressive weakening of the heart due to a deficiency in dystrophin, a protein required for muscle fibers to work properly. Early diagnosis can improve life expectancy through prophylactic treatment with heart medications. To combat this disorder, and others like it, the aforementioned partnership brings engineers and clinicians together to image the heart using 3D and 4D non-invasive methods. These are used to form personalized files and records that can compute heart function and determine important parameters that provide a more detailed look at the underlying condition. Many of these parameters are more common in a fluid mechanics course than in a doctor’s office, such as maps and measurements of the forces, stresses, strains and velocity profiles that can be mined to predict heart condition and prognosis that informs treatment plans. In some cases, the structures near the heart are printed on 3D printers for further study, or for communicating the prognosis and treatment plan to families through 3D models. Examples like these show the benefit of collaborating engineering and medicine expertise together.
This combination of engineering and personalization can also play a role in developing new drugs. One example of personalization is the mRNA technology that enabled COVID-19 vaccines; it is projected to be the basis of one-third of all new medicines by 2035 and is being applied to develop personalized cancer vaccines that can act on patient-specific tumor mutations. The personalization implies that medicines would need to be manufactured in much smaller volumes for groups of patients with similar needs. Another example is portable and modular manufacturing of medicines; these can be transported and operated in any location. The megatrend of miniaturization is finally reaching pharmaceutical manufacturing.
Unlike some innovations though, medicine-engineering breakthroughs cannot just blossom in someone’s garage, due to the highly regulated environment and vital nature of their end products. The disruptive changes of personalization, miniaturization and automation that are on the horizon for pharmaceutical industry were the focus of the inaugural Indiana Life Sciences Manufacturing Summit this month joined by leaders such as the Indiana Secretary of Commerce Brad Chambers. My home state of Indiana traces its strong pharma-manufacturing legacy to 1950s when the Indianapolis-based Eli Lilly and Company helped end America’s polio epidemic. Medicines and medical devices are still the largest export category for Indiana, totaling more than $11 billion annually. Indiana also places second in the United States for worldwide exports in life sciences and offers the highest per capita concentration of life sciences jobs.
We need more of these conversations that bring together state and local government, industry leaders and university researchers and community college educators. The goal is to forge global solutions with regional sources, and the workforce development that is needed to keep up with onshoring and accelerating technologies for medicine and medical devices. Such an innovation ecosystem in engineering medicine will be a critical part of a long-term strategy to enhance US manufacturing sovereignty and competitiveness.
Targeting medicine-engineering to “orphan diseases”