Case report suggests symptom improvement in patients with Bachmann-Bupp syndrome treated with DFMO — Evidence Review

A decades-old drug, difluoromethylornithine (DFMO), may offer the first potential therapy for Bachmann-Bupp syndrome (BABS), a life-threatening and ultra-rare genetic disorder, according to a new case series from Corewell Health and Michigan State University. Existing studies on rare disease treatments generally support the need for repurposed drugs and new therapies, aligning with the promise shown by DFMO for BABS.

• Repurposing established drugs for rare genetic conditions is a growing research trend, supported by previous studies that highlight substantial unmet needs and the lack of effective treatments in rare disease populations 8 11 12.
• The observed symptom improvements in BABS patients treated with DFMO are consistent with broader literature showing that innovative or adapted therapies can meaningfully improve outcomes in rare disease groups, even when standard options are limited 8 9 14.
• Despite progress, related studies emphasize ongoing challenges in rare disease drug development, including variable outcome measures, slow clinical trial advancement, and the need for further research to establish long-term safety and efficacy 5 9 13.

Study Overview and Key Findings

Bachmann-Bupp syndrome (BABS) is an ultra-rare neurodevelopmental disorder with no established treatments and only about 20 documented cases worldwide. The new study investigates the potential of DFMO, a drug initially developed for unrelated diseases, to improve symptoms in BABS patients. This effort is significant not only because BABS lacks any approved therapy, but also because it illustrates the challenges and opportunities of drug repurposing for ultra-rare conditions, including regulatory hurdles and limited awareness.

Below is the key study metadata:

Property	Value
Organization	Corewell Health, Michigan State University, Every Cure
Authors	Caleb Bupp, André Bachmann, Surender Rajasekaran, David Fajgenbaum
Population	Patients with Bachmann-Bupp syndrome
Sample Size	n=6
Methods	Case Report
Outcome	Symptoms improvement in patients treated with DFMO
Results	Many symptoms improved in treated patients

Literature Review: Related Studies

To contextualize these findings, we searched the Consensus paper database, which contains over 200 million research papers. The following search queries were used to identify relevant literature:

1. decades-old drug treatment outcomes
2. ultra-rare disease patient symptoms
3. long-term effects of rare disease therapies

Related Studies: Summary Table

Topic	Key Findings
What are the challenges and needs in developing therapies for ultra-rare diseases?	- Patients with rare diseases commonly face a lack of effective treatments and significant physical, mental, and financial burdens 8. - Diagnostic odyssey and variable outcome measures complicate both diagnosis and treatment evaluation in rare diseases, highlighting the need for more standardized outcomes and supportive infrastructure 5 7.
How effective are repurposed or longstanding drugs in rare and chronic diseases?	- Repurposed drugs and established therapies can meaningfully improve outcomes, as seen with enzyme replacement for Gaucher disease and beta-blockers for heart failure, but variability in results and outcome measures persists 2 9 14. - Long-term data support that therapy can reduce disease burden and improve quality of life, but patient-reported outcomes may not always align with clinical measures 9 14.
What long-term outcomes are observed in rare disease treatment?	- Long-term therapies can improve survival and function in certain rare diseases, but gaps remain in monitoring, patient experience, and standardized outcome reporting 10 14. - Gene and genetic therapies are expected to become standard care in the near future, offering hope for durable outcomes, though long-term safety and efficacy data are still emerging 11 12 13.
What are the common experiences and symptoms among patients with ultra-rare diseases?	- Patients often report multisystem involvement, repeated misdiagnoses, and ongoing physical and mental health challenges, underscoring the need for holistic and multidisciplinary approaches 6 7 8. - Symptom burden and quality of life impacts are shared across rare diseases, regardless of underlying etiology 8 9.

What are the challenges and needs in developing therapies for ultra-rare diseases?

The new DFMO study for BABS aligns with existing literature emphasizing the substantial unmet therapeutic needs in rare diseases. Many patients experience delays in diagnosis ("diagnostic odyssey") and limited access to effective treatments, often compounded by a lack of standardized outcome measures and supportive care infrastructure 5 7 8.

• Rare disease patients frequently lack effective therapies, face significant medical and psychosocial burdens, and experience diagnostic delays 7 8.
• The absence of consensus on outcome measures in rare disease studies hampers both research and clinical care 5.
• Increased awareness and interdisciplinary approaches are critical to improving diagnosis and care for ultra-rare disease populations 6 7.
• The new study's collaborative approach between clinical, academic, and nonprofit sectors reflects calls in the literature for more coordinated rare disease research and care infrastructure 8.

How effective are repurposed or longstanding drugs in rare and chronic diseases?

Repurposing established medications for rare diseases is a pragmatic strategy, given the lengthy and costly process of new drug development. The positive symptom improvements observed in BABS patients treated with DFMO are consistent with other research where repurposed or longstanding therapies have led to clinical improvement in rare or chronic conditions, although variability in outcomes and patient experiences remains 2 9 14.

• Long-term use of established therapies (e.g., enzyme replacement therapy, beta-blockers) has improved disease management and survival in other rare and chronic diseases 2 14.
• Patient-reported outcomes may highlight ongoing symptom burdens or unmet needs, even when clinical measures improve 9.
• Wide variation in outcome measures across studies suggests a need for standardized assessment of both clinical and patient-centered outcomes 5 9.
• The DFMO case series adds to growing evidence that drug repurposing can be an effective strategy for ultra-rare disorders with no existing treatment options 2 14.

What long-term outcomes are observed in rare disease treatment?

The literature indicates that long-term treatment can improve survival, function, and quality of life in some rare diseases, yet persistent gaps exist in monitoring, patient experience, and standardized outcome tracking 10 14. The introduction of genetic and gene-modifying therapies is expected to expand treatment options, but their long-term effects and safety profiles require further study 11 12 13.

• Longitudinal research demonstrates improved survival and organ function with disease-modifying therapies in certain rare diseases 10 14.
• Patient monitoring and real-world data collection remain challenging, with discordance sometimes observed between clinical and patient-reported outcomes 9 14.
• Gene therapy is poised to transform care for rare genetic diseases, but robust long-term safety and efficacy data are still needed 11 12 13.
• The DFMO study reflects the trend toward both repurposed and innovative therapies for rare conditions, emphasizing the need for rigorous long-term outcome studies 11 12.

What are the common experiences and symptoms among patients with ultra-rare diseases?

Patients with ultra-rare diseases, including BABS, often present with multisystem symptoms, undergo long diagnostic journeys, and face significant psychosocial and quality of life impacts 6 7 8 9. These challenges underscore the importance of holistic, multidisciplinary care and the need for both clinical and patient-reported outcome measures in evaluating new therapies.

• Patients frequently report physical, psychological, and social challenges, regardless of the specific rare disease 8 9.
• Experiences such as repeated misdiagnosis, multiple referrals, and ongoing unexplained symptoms are common in ultra-rare disease populations 7.
• Effective management of rare diseases requires comprehensive, multidisciplinary approaches, as reflected in the collaborative model of the DFMO study 6 8.
• Both clinical and patient-reported outcomes should be incorporated into future rare disease research and care models 9.

Future Research Questions

While this study offers promising early results for DFMO in treating BABS, significant questions remain. Future research is needed to confirm these findings in larger cohorts, define standardized outcome measures, and explore long-term safety and efficacy in this ultra-rare population.

Research Question	Relevance
What are the long-term safety and efficacy outcomes of DFMO in Bachmann-Bupp syndrome?	Long-term safety and sustained benefit are critical for any therapy in rare genetic diseases, but current data in BABS is limited to short-term case reports 10 11 12.
How can outcome measures for ultra-rare disease trials be standardized?	Standardized outcomes would facilitate trial design, enable comparison across studies, and improve regulatory and clinical decision-making in ultra-rare diseases 5 9.
What are the mechanisms by which DFMO improves symptoms in patients with ODC1 mutations?	Understanding the molecular and cellular mechanisms of DFMO's effects will inform both clinical use and future drug development for BABS and related disorders.
How do patient-reported outcomes compare to clinical outcomes in rare disease treatment?	There is often a mismatch between clinical and patient-reported outcomes, highlighting the importance of incorporating both perspectives in assessing treatment efficacy 9 14.
What are the barriers to conducting clinical trials in ultra-rare diseases and how can they be overcome?	Regulatory, financial, and logistical challenges often hinder clinical trial development in ultra-rare diseases, as highlighted in the BABS-DFMO collaboration and related literature 5 7 8.