Rapid developments in paediatric neurology: Keeping up with the patient's voice

2022 has seen the arrival of more disease modification therapies for children and worldwide collaborations have expedited their introduction. It remains to be seen whether the disruptive nature of the pandemic to clinical services was outweighed by the leap in telemedicine and international communication. Technologies have been leapfrogging, such as antisense oligonucleotide (ASO) therapy for spinal muscular atrophy (SMA) type 1, which has been followed by gene therapy. The modes of genomic therapy are wider than one could have envisaged previously – from lentiviral assisted treatments, to exon skipping and ultimately, full genomic replacements. Mode of administration and targeted cell types varies considerably between technologies, such as the recent development of a UK National Health Service clinical program for metachromatic leukodystrophy with venous delivery of the viral vector. Animal models demonstrate potentially greater efficacy with more targeted and multiple central nervous system injections in other white cell enzyme disorders. 2022 has seen a further upshift in the development of both diseasespecific and more precise therapies for genomic disorders, including their availability for prescription as they gain UK, European, and international licences. The efficacy of fenfluramine in SCN1Arelated epilepsies has been demonstrated in a robust randomized controlled trial. This showed better outcome than many other treatments in both this/other early onset epilepsies, as well as reassuring data regarding tolerability/safety. Many studies are proposed for other genomic epilepsies, or stratifying larger populations so that the effects can be analysed in smaller groups. The above developments were unlikely to have occurred without the patient voice. The older neurologist will remember the emotive tale of dietary modification in adrenoleukodystrophy that was made into the film Lorenzo's Oil. There are now many examples where families and small organizations have pushed for new therapies. A good example of this would be the development of an ASO to treat Angelman syndrome. This was initially proposed and developed by parents of a child affected by this condition, with subsequent development of a patient organization, research group, multiple grants, and a biotech company – with phase 1 clinical trials (https://curea ngelm an.org/resea rch#FFRes earch). There continues to be substantial clinical challenges. Early enthusiasm for ASO therapy in SMA type 1 has been dented by poor response when treatment is later in the journey, with neonatal/newborn infant screening being a necessary next step to start presymptomatic/early treatment. Altering these protocols is a Herculean task. We should plan for setbacks, the combined voice of both the professional and parent/carer community is essential in challenging the existing paradigm. For wider dissemination of ‘curative’ technologies, funders need robust data on efficacy, that reflects the issues that parents/carers, children, and young people believe are important – particularly their quality of life (QoL). This emphasizes the importance of QoL assessment, but also tools assessing the areas that are prioritized by the relevant population – well reported for autism spectrum disorder. The BPNA Conference in 2023 will cover many of the above issues. There will be reporting on advanced medical therapies and careful review of the outcome measures that are being reported. The volume of the patient and carer voice will be louder, although possibly not as loud as we need it to be. We will be hearing from children of their realworld experience, as well as from parents who have both proposed and developed advanced therapies. We hope that 2023 will be a year when these issues come together to allow further development of advanced therapies, based on the need identified by families, supported with robust, patient/groupappropriate data on outcome including QoL.