Why this study matters

Bardet-Biedl syndrome (BBS) is a genetically diverse condition caused by changes in genes involved in the function of cilia—tiny structures that help cells sense and respond to their environment. For many people with BBS, intense, persistent hunger (hyperphagia) and obesity are major health challenges. Kidney disease is also a key feature of the condition and can be severe enough to require transplantation in childhood.

Setmelanotide is a treatment designed to act on a brain pathway involved in hunger and energy balance. However, there is limited evidence about its use in children with BBS who have received a kidney transplant. This 2026 report describes the experiences of two genetically confirmed pediatric kidney transplant recipients treated with setmelanotide. Their different outcomes underline both the potential of the therapy and the need to understand why responses can vary so widely between individuals.

Two children with BBS, different treatment trajectories

The researchers collected information on body weight, body mass index (BMI), hunger, metabolic measures, kidney graft function, cyclosporine blood levels, and genetic findings while the children received setmelanotide.

Patient 1: Sustained improvements over 12 months

The first patient was a 17-year-old boy with a homozygous pathogenic deletion affecting an exon of SDCCAG8, a BBS-associated gene. Over 12 months of treatment, he experienced improvements across several measures:

  • Weight decreased from 55.6 kilograms to 48.0 kilograms.
  • BMI decreased from 26.6 to 23.0 kg/m².
  • His BMI-for-age z-score—a measure comparing BMI with that of children of the same age and sex—fell from +1.60 to +0.43.
  • His maximum hunger score decreased from 8 out of 10 to 5 out of 10.
  • HbA1c, a marker of average blood glucose over recent months, improved from 6.5% to 5.1%.

Together, these findings suggest that setmelanotide was associated with reduced hunger, weight loss, and improved glucose-related metabolic health in this patient.

Patient 2: Early hunger and BMI improvement, but no sustained weight benefit

The second patient was an 8-year-old girl with a homozygous likely pathogenic splice-site variant in BBS5. She also carried one copy of the PCSK1 N221D variant. The possible role of this additional variant in her treatment response remains uncertain.

She reported reduced hunger after starting setmelanotide. By approximately two and a half months, her BMI-for-age z-score declined from +6.10 to +5.69. This decrease exceeded the study’s 0.2-point threshold for a clinically meaningful change. However, the improvement was not sustained. By eight months, her BMI had increased from 38.0 to 42.7 kg/m² despite treatment at 3 mg per day.

Her experience is important because it shows that an early reduction in hunger or BMI may not necessarily translate into continued weight benefit for every child.

Reassuring observations for transplant monitoring

For families and clinicians, a central question is whether a medicine used to address hyperphagia and obesity could affect a transplanted kidney or interfere with anti-rejection treatment. In these two cases, kidney graft function remained stable during setmelanotide treatment. Cyclosporine trough concentrations—the blood levels measured to help guide dosing of this immunosuppressive medicine—also remained stable.

Skin hyperpigmentation, or darkening of the skin, was the only treatment-related adverse effect reported. Importantly, the authors emphasize that two cases cannot establish the overall safety of setmelanotide after kidney transplantation. Still, the observations provide early information that can help shape future studies and clinical monitoring.

What this could mean for treatment approaches

This report supports a personalized approach to treating hyperphagia and obesity in BBS, particularly in people with complex medical histories such as kidney transplantation. Setmelanotide may offer meaningful benefit for some individuals, as illustrated by the sustained improvements seen in the first patient. But the second patient’s course shows that response cannot be assumed based on a BBS diagnosis alone.

Genetic differences may be one reason responses vary. The two children had different BBS-associated genetic findings, and the second child also had a PCSK1 variant. This report cannot determine whether those genetic factors caused the different outcomes, but it raises an important question for future research: can genetic information help predict who is most likely to benefit from setmelanotide?

The study also highlights practical measures that may be useful when evaluating treatment response: tracking hunger alongside weight and BMI, following metabolic markers such as HbA1c, and closely monitoring graft function and immunosuppressant concentrations in transplant recipients.

Building a clearer evidence base

These two cases are hypothesis-generating rather than definitive. Larger studies, longer follow-up, and participation from more children and adults with BBS—including those with kidney transplants—will be needed to better define effectiveness and safety. Research may also clarify whether specific BBS genes or additional genetic variants influence response.

For the BBS community, the report represents a meaningful step toward understanding how treatment for hyperphagia and obesity can be tailored to individuals with substantial kidney involvement. It reinforces a central lesson of rare-disease research: even when patients share a diagnosis, their biology, clinical needs, and response to therapy may differ.