A History of Margie's Involvement in Homocystinuria
Margie's involvement in homocystinuria (HCU) began with a profound personal loss that would shape the course of her life's work. In 1963, her sisters, Judy and Susie, were diagnosed with classical homocystinuria at the ages of six and two. At that time, little was known about the disorder, and treatment options were virtually nonexistent. Over the following years, both girls suffered devastating complications of HCU, including blood clots, strokes, ophthalmologic issues, and cognitive impairment. In 1971, Margie lost both
sisters—Judy at age 14 from a stroke and Susie at age 9 from a pulmonary embolism. At just 11 years old, she made a promise to herself that someday she would do something to change the future for families affected by HCU.
After a successful 26-year career at Merck, Margie decided it was time to fulfill that promise. She took early retirement and established the Hempling Foundation for Homocystinuria Research, funding it through Merck stock she had accumulated during her career. Drawing on advice from former colleagues in pharmaceutical research and inspired by the work of John Crowley, whose efforts led to a treatment for his
children with Pompe disease, Margie developed a strategy focused on supporting early-stage research that could demonstrate proof of concept and eventually attract pharmaceutical or biotechnology partners capable of bringing therapies to patients.
A pivotal moment came when Margie connected with Dr. Jan Kraus while pursuing genetic testing for her family. In addition to helping identify carriers within the family, Dr. Kraus shared his research on enzyme replacement therapy for HCU. Recognizing the promise of this approach, Margie provided a research grant in 2012 that helped support the foundational work leading to the development of what is now pegtibatinase, currently in Phase 3 clinical trials. Margie later played an active role in facilitating the licensing of this technology to Orphan Technologies and served on its board for several years before the program was acquired by Travere Therapeutics in 2020.
Through Dr. Kraus and the pioneering physician scientist Dr. Harvey Mudd, Margie became connected with many of the leading researchers in the HCU field. Dr. Mudd shared the early history of identifying cystathionine beta-synthase deficiency as the underlying cause of classical HCU and introduced Margie to investigators around the world. One such researcher was Dr. Warren Kruger at Fox Chase Cancer Center, whose work on chaperone therapies demonstrated that stabilization of certain defective CBS enzymes was scientifically feasible, even though the compounds tested were ultimately not suitable for long-term clinical use.
Over the following years, the Hempling Foundation funded numerous additional research initiatives, including studies on disease incidence, newborn screening, and gene therapy. One gene therapy program, conducted in collaboration with Dr. Ron Crystal at Weill Cornell Medicine, demonstrated particularly promising results. Although commercial development partners have not yet been secured, efforts to advance this work continue.
Margie's commitment extended beyond research to building a stronger patient and family community. In 2011, she met Danae Bartke at a patient and family gathering in Colorado organized by a geneticist who believed families affected by HCU should be connected. Although initial efforts to establish a U.S. patient organization were unsuccessful, the idea persisted.
Several years later, Margie and Danae connected with Tara Morrison of Australia, who had established a patient advocacy organization there and was organizing an international HCU expert meeting in Prague in 2016. Attending this meeting proved transformative. Witnessing the dedication of researchers, clinicians, and advocates from around the world reinforced the urgent need for both expanded research efforts and a formal patient advocacy organization in the United States.
Following the Prague meeting, Margie and Tara established a global Scientific Advisory Board and research grants program, funding multiple projects in classical HCU and newborn screening. Simultaneously, Margie and Danae worked tirelessly to establish HCU Network America. Through pro bono legal and consulting support, they successfully incorporated the organization and obtained 501(c)(3) status by the end of 2016.
From its earliest days, HCU Network America benefited from Danae Bartke's exceptional leadership. Under her guidance, the organization expanded its advocacy efforts in newborn screening, contributing to improvements in state screening practices and supporting the development of enhanced testing methodologies through the CDC. Recognizing unmet needs within the broader homocystinuria community, the organization also expanded its mission to include support for individuals and families affected by cobalamin and MTHFR disorders, broadening both patient services and research funding opportunities.
Together, Margie, Danae, and a dedicated board of directors and advisors built a thriving organization that established research grant programs, organized national patient and family conferences, expanded staff and volunteer engagement, and strengthened partnerships throughout the rare disease community. In 2021, Margie further advanced patient care by endowing a Chair in Clinical Pharmacy at the University at Buffalo to improve medication management and support for individuals with metabolic disorders.
In 2026, after serving as President of HCU Network America since its founding, Margie stepped down due to term limits and assumed the role of Emeritus Director. Although no longer involved in governance decisions, she remains committed to supporting the organization's mission. As HCU Network America celebrates its 10th anniversary, Margie takes pride in the extraordinary progress that has been achieved through the collective efforts of patients, families, researchers, clinicians, advocates, and volunteers, and remains optimistic about the future advances yet to come.
