Genespire has started enrolling children with severe methylmalonic acidemia in an international observational study supporting development of GENE202 gene therapy.

Genespire has started patient enrolment in an international observational study designed to build a detailed picture of disease progression in children with severe methylmalonic acidemia (MMA).

The Italian biotech is conducting the prospective, multicentre InforMMA study in children aged up to 16 with MMA caused by mutations in the MMUT gene. The study will collect longitudinal clinical and biochemical data over 36 months, with the findings intended to inform development of Genespire’s investigational GENE202 gene therapy.

InforMMA will enrol patients with severe MMA both with and without a history of liver or kidney transplantation. Researchers will measure biochemical markers and clinical outcomes associated with metabolic stability and disease progression over the study period.

The study will involve seven specialist metabolic and paediatric centres across the US and Europe, including Great Ormond Street Hospital in London, Ospedale San Raffaele and Ospedale Pediatrico Bambino Gesù in Italy, and Children’s Hospital of Philadelphia in the US.

Study aims to address gaps in MMA data

Genespire said the observational study will provide longitudinal information on the course of severe MMUT-associated MMA, which it hopes will help inform later stages of GENE202 development.

“Observational studies like this require time, resources and close collaboration with the wider community – but they are fundamental to innovation in rare disease,” said Lucia Faccio, CEO of Genespire. “By investing early in our understanding of MMA, we aim to optimize the later stages of development for GENE202.”

MMA is a rare inherited metabolic disorder most commonly caused by mutations affecting the MMUT gene, which provides instructions for the methylmalonyl-CoA mutase enzyme. Deficiency of the enzyme can result in the accumulation of methylmalonic acid and other metabolic abnormalities, contributing to damage affecting organs including the brain and kidneys.

Genespire is developing GENE202 as an immune-shielded lentiviral vector (ISLV) gene therapy for MMA. The company says the approach is designed to deliver a functional MMUT gene to liver cells following intravenous administration.

International study will follow patients for 36 months

The InforMMA study is registered on ClinicalTrials.gov as NCT07432880 and will include sites in the US, Italy, Spain and the UK.

The European sites are Ospedale San Raffaele and Ospedale Pediatrico Bambino Gesù in Italy, Hospital Sant Joan de Déu and Hospital Universitario 12 de Octubre in Spain, and Great Ormond Street Hospital in the UK. US sites are Children’s Hospital of Philadelphia and UPMC Children’s Hospital of Pittsburgh.

Maddalena Migliavacca, principal investigator at the Ospedale San Raffaele site, said: “For far too long, patients with MMA have been underserved by healthcare systems and underrepresented in research, leaving substantial gaps in our understanding of disease progression over time.”

She added that the study aims to provide a more detailed understanding of the patient experience and could contribute to efforts to improve outcomes for patients and their families.

Genespire’s GENE202 programme is being developed for a disease for which there are currently no approved disease-targeted treatments. The company received orphan drug designation from both the US Food and Drug Administration and European Commission for GENE202 in January 2026.

The company has previously said it aims to take GENE202 into clinical development, with the candidate described as its lead programme for MMA.

The InforMMA dataset will therefore provide Genespire with prospective information on disease progression as it advances the gene therapy programme towards clinical testing.