Gene therapy’s pipeline is overwhelmingly paediatric
Many of the conditions that one-time genetic treatments target first appear in infancy. That puts children at the centre of the field’s scientific, commercial and ethical debates.
In brief
Why gene therapy targets children first: early irreversible disease, newborn screening, AAV durability in growing bodies and one-time treatment costs.
- Many monogenic diseases cause irreversible damage early, which pushes treatment towards the youngest patients.
- Newborn screening and gene therapy are increasingly developed together.
- Durability, immune responses to vectors and price remain the field’s open questions.
Gene therapy’s defining approvals have often been for diseases that strike early in life. Onasemnogene abeparvovec, approved by the FDA in 2019 for spinal muscular atrophy in children under two, became the reference case for what a single infusion can do, and for what it can cost.
Why children come first
Most gene therapies target monogenic diseases: conditions caused by a fault in a single gene. Many of these begin in infancy or early childhood and cause damage that cannot be reversed, such as the loss of motor neurons in spinal muscular atrophy. Treating before that damage occurs preserves function that later treatment cannot restore.
That logic pushes development towards the youngest patients, and towards finding them before symptoms start. Newborn screening programmes and gene therapy developers now have a shared interest in adding conditions to screening panels.
Technical questions specific to children
Most in vivo gene therapies use adeno-associated virus (AAV) vectors. AAV genomes largely stay separate from the patient’s chromosomes, so in tissues where cells keep dividing, as they do in a growing child, the therapeutic gene can be diluted over time. That raises the question of whether a treatment given in infancy will last into adulthood.
Pre-existing antibodies to AAV can rule patients out, and once treated, a patient will usually develop antibodies that make redosing difficult. Dose is typically calculated by body weight, so treating smaller children can also mean lower manufacturing cost per patient.
The questions that follow
Long-term follow-up is still building, since the earliest trial participants were treated only around a decade ago. Regulators require years of monitoring after approval. Pricing models that spread payment over time, or tie it to outcomes, are being tested by payers on both sides of the Atlantic.
The field also faces an ethical tension. When a disease is rare and rapidly fatal, families and regulators may accept more uncertainty than they would elsewhere. Getting that balance right, without either stalling progress or approving therapies that do not deliver, is the central challenge of paediatric gene therapy.
