Researchers publish promising results for ultra-rare disease gene therapy method

Researchers have published some promising results for a new gene therapy method that may offer hope for children born with the ultra-rare genetic disease aromatic amino acid decarboxylase (AADC) deficiency.

The study, conducted by researchers at the Ohio State University Wexner Medical Centre and the Ohio State University College of Medicine in the US, evaluated the targeted delivery of gene therapy to two regions of the midbrain – the substantia nigra pars compacta (SNc) and the ventral tegmental area (VTA).

AADC is characterised by a deficiency in AADC, an enzyme involved in the synthesis of neurotransmitters – dopamine and serotonin – which are responsible for the communication between neurons in the nervous system.

Approximately 135 patients are known to have this condition across the world, although the true incidence is currently unknown.

Symptoms of this disease include decreased muscle tone, movement disorders, developmental delay, restricted growth and disruption of the automatic nervous system.

Patients can also experience oculogyric crises that are characterised by intermittent or sustained tonic vertical, horizontal or convergent deviation of the eyes and sometimes accompanied by other involuntary movements of the face and body.

According to researchers, targeted gene therapy treatment in seven children aged four to nine years old provided ‘dramatic’ improvement of symptoms, motor function and quality of life.

“Twelve months after surgery, 6/7 subjects gained normal head control and 4/7 could sit independently. At 18 months, 2 subjects could walk with 2-hand support. Both the primary and secondary endpoints of the study were met. Midbrain gene delivery in children with AADC deficiency is feasible and safe, and leads to clinical improvements in symptoms and motor function,” wrote the US researchers.

“This work provides a framework for the treatment of other human CNS genetic diseases, and iterative refinement of the individual components of this approach will facilitate broader application,” they concluded.

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