Repurposed Sleeping Sickness Drug Shows Promise for Ultra-Rare Bachmann-Bupp Syndrome
核心洞察
Eflornithine (DFMO), a decades-old drug originally used for West African sleeping sickness (搜索), has shown promising results in treating Bachmann-Bupp syndrome (搜索) (BABS (搜索)), an ultra-rare genetic disorder affecting only about 20 patients worldwide.
Five BABS (搜索) patients treated with DFMO through FDA single-patient protocols have demonstrated visible improvements in muscle tone, developmental milestones, and hair growth by targeting the overactive ODC1 (搜索) enzyme pathway.
A new collaboration between Corewell Health, Michigan State University, and Every Cure (搜索) aims to accelerate research and navigate regulatory pathways to bring this potential treatment to more patients with the rare genetic condition.
A decades-old drug originally developed to treat West African sleeping sickness (搜索) is offering new hope for families affected by one of the world's rarest genetic disorders. Eflornithine, also known as difluoromethylornithine (搜索) (DFMO), has shown promising early results in treating Bachmann-Bupp syndrome (搜索) (BABS (搜索)), a devastating condition that affects only about 20 diagnosed patients worldwide.
The breakthrough emerged from a collaboration between Dr. Caleb Bupp at Corewell Health and Dr. André Bachmann at Michigan State University, who connected a Michigan child's symptoms to the underlying genetic mechanism and moved from diagnosis to treatment in just 16 months.
Targeting the Root Cause
BABS (搜索) is caused by gain-of-function mutations in the ornithine decarboxylase (搜索) (ODC1 (搜索)) gene, which leads to overactivity of the ODC enzyme. This excessive enzyme activity results in serious developmental challenges, including significant delays, low muscle tone, and hair loss in affected children.
DFMO works by directly inhibiting the ODC protein, reducing the excessive enzyme activity caused by the mutated gene. "By slowing the enzyme, DFMO lowers excess putrescine, a cell chemical linked to growth and may ease the symptoms downstream," according to the research findings.
Dr. Bachmann, who has studied DFMO and its effects on the ODC1 (搜索) gene for three decades, explained: "It was a chance encounter with Dr. Bupp that we connected and were able to use DFMO on a patient -- and now five others -- with promising early results."
Visible Clinical Improvements
The five BABS (搜索) patients treated so far through FDA-approved single-patient investigational protocols have shown encouraging responses. Families and clinicians have reported visible improvements in daily movement, development, and hair growth. Specifically, doctors observed steadier muscle tone, achievement of new developmental milestones, and hair regrowth in treated patients, though the timing and extent of improvements varied among individuals.
These visible changes represent significant hope for families who previously had few options beyond diagnosis. However, researchers acknowledge that the small treated group cannot definitively show whether age, specific gene variants, or baseline symptoms influenced each patient's response.
Advantages of Drug Repurposing
DFMO's appeal lies in its established medical history. The drug has been used to treat West African sleeping sickness (搜索), reduce unwanted facial hair in women, and prevent neuroblastoma (搜索) relapse in children. In 2023, the FDA approved oral eflornithine to reduce relapse risk in high-risk neuroblastoma, a nerve-cell cancer.
This extensive background provides researchers with crucial advantages, including dosing guidelines, known side effects, and safety experience in children requiring long-term treatment. "Doctors already know far more about it than they would a brand-new medicine," the research indicates.
Overcoming Rare Disease Challenges
The extreme rarity of BABS (搜索) presents significant obstacles to traditional clinical development. With only about 20 diagnosed patients worldwide, the condition lacks sufficient numbers for large-scale trials typically required to establish treatment efficacy. A 2024 federal report found that while nearly one in ten Americans have a rare disease, only about five percent of rare diseases have approved treatments.
"For the past year, we've been at a standstill as far as moving our DFMO therapy forward," Dr. Bupp acknowledged, citing regulatory requirements and the complexity of launching clinical trials as key hurdles.
New Partnership Accelerates Progress
To address these challenges, a new collaboration has formed between Corewell Health, Michigan State University College of Human Medicine, and Every Cure (搜索), a nonprofit biotech organization focused on finding new uses for existing drugs.
"Beyond helping us build preclinical studies and retrospective analyses, the team at Every Cure (搜索) has already begun helping us navigate regulatory pathways and compliance on so many levels in the hopes that we can treat more of our BABS (搜索) patients," said Dr. Bupp. "They are opening doors that we never would have been able to crack open."
Dr. David Fajgenbaum, co-founder and president of Every Cure (搜索), outlined their role: "Our role is to help bridge this gap by strengthening the evidence behind BABS (搜索) and DFMO through preclinical studies, increasing awareness among physicians and rare disease organizations, and ensuring that no child goes undiagnosed or untreated."
Looking Forward
The partnership has already begun building on years of prior research, with a preclinical study expected to begin next year. This represents an important step toward potentially bringing the therapy to more patients.
However, researchers emphasize that important questions remain. Future studies must determine who will benefit most from treatment, when therapy should begin, and which clinical signs indicate lasting improvement. Additionally, diagnostic guidance warns that uncertain ODC1 (搜索) gene changes do not definitively establish or rule out BABS (搜索), and in at least one reported case, a child with an unusual variant did not show elevated enzyme activity above control samples.
The research findings have been published in the American Journal of Medical Genetics Part C: Seminars in Medical Genetics, marking a significant milestone in the journey from a forgotten medicine to a potential lifeline for families facing this ultra-rare genetic disorder.