Sleeping Sickness Drug Shows Promise for Rare Bachmann-Bupp Syndrome

A decades-old drug previously used to treat sleeping sickness is showing potential as a treatment for Bachmann-Bupp syndrome (BABS), an extremely rare and life-threatening genetic disorder. Early treatments with the drug, difluoromethylornithine (DFMO), have demonstrated encouraging results in easing severe symptoms by targeting the underlying genetic malfunction, according to a collaboration between Corewell Health, Michigan State University, and Every Cure.

Currently, there are only 20 diagnosed cases of BABS worldwide. The drug’s potential was first identified through a partnership aimed at repurposing existing medications for rare diseases. “Beyond helping us build preclinical studies and retrospective analyses, the team at Every Cure 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 patients,” said Caleb Bupp, M.D., a pediatric geneticist at Corewell Health Helen DeVos Children’s Hospital in Grand Rapids.

What is Bachmann-Bupp Syndrome?

Bachmann-Bupp syndrome is a genetic disorder caused by mutations in the ornithine decarboxylase (ODC1) gene. These mutations lead to severe neurodevelopmental delays, poor muscle tone, and hair loss. DFMO works by inhibiting the ODC protein, effectively slowing down the activity of the mutated gene and potentially mitigating the symptoms of BABS.

Marley Berthoud of Mattawan, Michigan, was the first patient to be diagnosed with Bachmann-Bupp Syndrome, with the assistance of Dr. Bupp. Her case helped to bring awareness to the disorder and spurred research into potential treatments.

Drug Repurposing and Regulatory Challenges

The use of DFMO for BABS represents a prime example of drug repurposing – identifying new uses for existing medications. This approach can significantly accelerate the development of treatments for rare diseases, as the drug has already undergone safety testing for its original intended use. However, even with a known safety profile, bringing a repurposed drug to market for a new indication presents significant regulatory hurdles.

The collaboration with Every Cure, a nonprofit biotech group, is proving crucial in navigating these regulatory pathways. The organization is assisting researchers with compliance and the necessary steps to expand treatment access to more BABS patients. Researchers have already treated a handful of patients under an FDA-approved, single-patient investigational protocol.

Historical Use of DFMO

Difluoromethylornithine, also known as eflornithine, has a history of use in treating several conditions. It was originally developed to treat African sleeping sickness, a chronic parasitic infection. It is also currently used to reduce unwanted facial hair growth in women and to prevent the recurrence of neuroblastoma, a type of cancer that primarily affects children.

The discovery that DFMO might be effective against BABS stemmed from understanding its mechanism of action – its ability to inhibit the ODC protein. This led researchers to investigate its potential in addressing the underlying genetic cause of the syndrome.

Future Directions

While the early results are promising, further research is needed to fully understand the long-term effects of DFMO treatment for BABS. Researchers are continuing to build preclinical studies and retrospective analyses to gather more data and refine treatment protocols. The primary goal is to secure broader access to DFMO for all patients who could benefit from this potentially life-changing therapy.

The success of this collaborative effort highlights the potential of combining clinical expertise, academic research, and nonprofit support to address the challenges of rare disease treatment. The team hopes that their work will pave the way for new therapies and improved outcomes for individuals affected by BABS and other rare genetic disorders.