Decades-Old Drug Show Promise as Treatment for Ultra-Rare Disorder

Rare Daily Staff

A decades-old drug originally developed to treat a tropical disease is offering new hope to children with one of the rarest genetic disorders in the world.

Researchers in Michigan say early results suggest that difluoromethylornithine, better known as DFMO, may help treat Bachmann-Bupp syndrome (BABS), a life-threatening condition that has been diagnosed in only about 20 people worldwide.

The disorder was first identified in a young patient, Marley Berthoud of Mattawan, Michigan, by Caleb Bupp, a pediatric geneticist at Corewell Health. BABS is caused by mutations in a gene called ODC1, leading to abnormal enzyme activity that results in severe developmental delays, low muscle tone, and hair loss.

Now, scientists believe DFMO may directly counteract that genetic malfunction.

“It’s a hopeful and exciting time,” said Bupp, who has been leading efforts to treat patients. “More importantly, it’s hopeful for our patients.”

DFMO is not a new drug. It has been used for decades to treat African sleeping sickness, a parasitic infection spread by tsetse flies. It is also prescribed in some cases to help prevent relapse in pediatric cancer and to reduce unwanted facial hair. Its ability to block the ODC enzyme has made it a promising candidate for BABS.

In a small number of patients treated so far, six in total, doctors have seen encouraging improvements in symptoms. These treatments were carried out under special FDA-approved protocols that allow experimental use on an individual patient basis.

The idea to try DFMO in BABS builds on years of research into the ODC1 gene. Michigan State University scientist André Bachmann, who has studied the drug for decades, collaborated with Bupp after the syndrome was first identified.

Despite the early promise, progress has been slow.

Because BABS is so rare, researchers face major challenges in identifying patients, raising awareness, and designing clinical trials. Regulatory hurdles have also delayed efforts to move forward with broader studies, even as the FDA has encouraged a formal trial.

“For the past year, we’ve been at a standstill,” Bupp said.

Now, the nonprofit Every Cure is stepping in to help accelerate the work. The organization focuses on repurposing existing drugs for new diseases and is helping researchers navigate regulatory requirements, strengthen the evidence base, and connect with rare disease communities.

“Our goal is to ensure no child goes undiagnosed or untreated,” said David Fajgenbaum, co-founder of Every Cure.

A preclinical study is expected to begin next year, which researchers hope will pave the way for larger trials and potentially make the treatment more widely available.

For families affected by BABS, even incremental progress is meaningful. A drug once used for a parasitic disease may now offer a lifeline where none previously existed.

Photo: Caleb Bupp, a pediatric geneticist at Corewell Health