Investigating attitudes toward prenatal diagnosis and fetal therapy for spinal muscular atrophy

Abstract

Objective: In utero SMA treatment could improve survival and neurologic outcomes. We investigated the attitudes of patients and parents with SMA regarding prenatal diagnosis, fetal therapies, and clinical trials. Methods:A multidisciplinary team designed a questionnaire that Cure SMA electronically distributed to parents and patients (>18 years old) affected by SMA. Multivariable ordinal logistic regression was used to analyze associations between respondent characteristics and attitudes.Results: Of 114 respondents (60% of whom were patients), only 2 were prenatally diagnosed. However, 91% supported prenatal testing and 81% felt there had been a delay in their diagnosis. Overall, 55% would enroll in a phase I trial for fetal antisense oligonucleotide (ASO) while 79% would choose an established fetal ASO/ small molecule therapy. Overall, 61% would enroll in fetal gene therapy trials and 87% would choose fetal gene therapies. Patients were less likely to enroll in a fetal gene therapy trial than parents enrolling a child (OR 0.31, p < 0.05). Older parental age and believing there had been excessive delay in diagnosis were associated with an interest in enrolling in a fetal ASO trial (OR 1.04, 7.38, respectively, p < 0.05). Conclusion:In utero therapies are promising for severe genetic diseases. Patients with SMA and their parents view prenatal testing and therapies positively, with gene therapy being favored. Key pointsWhat's already know about this topic?� Optimal therapeutic outcome in many SMA patients is limited by motor neuron pathology that begins prenatally and is incompletely reversed by treatment delivered postnatally. In a preclinical model, in utero delivered therapeutics have successfully ameliorated the SMA phenotype. Involving the patient and caregiver community is crucial as we consider the pathway to a first in-human clinical fetal therapy trial for rare diseases, such as SMA.

Preemptive dual therapy for children at risk for infantile‐onset spinal muscular atrophy

“…It appears most people who have experienced SMA as a patient or parent are willing to accept these risks. A relatively recent survey distributed by CureSMA (https://www.curesma.org) was completed by 114 respondents whose lives were affected by SMA (60% patients and 40% parents): overall, 91% supported prenatal testing, 61% would enroll in fetal gene therapy trials, and 87% would choose fetal therapy with an approved agent 56 . To the extent that fetal therapy gains traction, our growing prospective dual therapy (2D) cohort can serve as an important source of external comparator data for future clinical trials (https://www.fda.gov/media/164960/).…”