Treatment of spinal muscular atrophy with onasemnogene abeparvovec: off-label case report and follow-up protocol proposal

Case presentation: Male patient whose hypotonia was observed around 2 months-old. He was diagnosed with Spinal Muscular Atrophy (SMA) when he was 4 months-old - heterozygous deletion of the SMN1 gene (1 copy of exon 7 and exon 8), 2 copies of SMN2 (2 copies of exon 7 and exon 8 8). In the copy of SMN1, a p.Pro246Thrfs*10 variant is observed, characterizing a compound heterozygosity. This patient always had has an excellent multidisciplinary follow-up – motor and respiratory physiotherapy, speech therapy, occupational therapy, several times per week. He is periodicaly evaluated by pediatrician, child neurologist, orthopedist, pulmonologist and nutritionist. He uses BIPAP and has a gastrostomy to supplement oral feeding. He has never been hospitalized for respiratory or other complications, only for elective gastrostomy. He begun the treatment with nusinersene when he was 8 months-old, having applied 12 doses. The last dose was at 3 years and 5 months-old. At 3 years and 6 months-old, he had the onasemnogene abeparvovec application. He evolved with an increase in hepatic transaminases and required corticosteroid therapy for 19 weeks. In general terms, he always had a good evolution, but, apparently, he increased the speed of gaining points on the CHOP INTEND scale after the application of gene therapy. He also improved his ventilometry. In addition, he has been able to feed more quickly, better handling the accumulation of saliva in the mouth and his speech is less interrupted and presents a more audible tone.

Discussion: The new era of therapies for SMA broke paradigms and created a new reality. Currently, there is extensive discussion about which therapy would be most suitable for each case. Thus, the need arises to define parameters that can guide and assist in these choices, especially in patients considered off-label. The case has shown a better evolution compared with its peers described so far in the literature – patients who have received gene therapy older than 24 months-old. We believe that this is highly related to the good clinical condition of the patient, combined with the therapies and the fact that he has a compound heterozygosity.

Final comments: Through this case report, we would like to share the clinical experience with an off-label patient who received gene therapy, presenting a suggestion for a protocol of pre-infusion and follow-up exams, which can provide greater confidence in the diagnosis and management of possible complications - more incidents in this profile of patient.

 

MissingLinkText

No conflict of interest has been declared by the author(s).

Publication History

Article published online:
18 September 2023