A drug with a long medical history is showing early promise for one of the rarest genetic disorders on record.
Researchers at Corewell Health and Michigan State University, working with nonprofit biotech group Every Cure, say difluoromethylornithine, also known as DFMO or eflornithine, may help treat Bachmann-Bupp syndrome, or BABS, a life-threatening genetic disorder with only about 20 reported cases worldwide.
The drug has been used to treat West African sleeping sickness, a chronic parasitic illness spread by the tsetse fly. It is also used to reduce unwanted facial hair in women and to help prevent neuroblastoma from returning.
Researchers have now given DFMO to a small number of BABS patients through an FDA-approved, single-patient investigational protocol.
BABS is caused by gain-of-function mutations in the ODC1 gene. According to Corewell Health, those mutations can cause serious developmental challenges including significant delays, low muscle tone and hair loss.
DFMO works by inhibiting the ODC protein, which reduces the excessive enzyme activity caused by the mutated gene. In the limited number of patients treated so far, researchers said the approach has led to improvements in several symptoms.
“I’ve studied DFMO and its effect on the ODC1 gene for three decades, including its clinical use in pediatric neuroblastoma,” said Michigan State University pediatrics professor André Bachmann, PhD, who with Dr Caleb Bupp was the first to identify BABS in a patient.
“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.”
Dr Bupp, a pediatric geneticist for Corewell Health Helen DeVos Children’s Hospital in Grand Rapids, said the partnership with Every Cure is helping the team move the work forward.
“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,” he said.
“They are opening doors that we never would have been able to crack open. It’s a hopeful and exciting time for all of us and more importantly, our patients.”
Despite the early signs, researchers said progress has been slow because the disorder is so rare and because of the demands involved in setting up clinical trials.
Although the US Food and Drug Administration has encouraged Drs Bupp and Bachmann to move toward a formal trial, the team still has to define study goals and reach enough patients.
“For the past year, we’ve been at a standstill as far as moving our DFMO therapy forward,” Dr Bupp said.
Every Cure said it is helping strengthen the scientific evidence, raise awareness among physicians and rare disease groups, and support systems to identify and treat patients as the research continues.
“Our role is to help bridge this gap by strengthening the evidence behind BABS and DFMO through preclinical studies, increasing awareness among physicians and rare disease organizations, and ensuring that no child goes undiagnosed or untreated,” said David Fajgenbaum, MD, co-founder and president of Every Cure.
The groups said a preclinical study is expected to begin next year.
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