Across these ethical considerations, the researchers emphasize the importance of collaborating with patients and their caregivers.
Amidst a changing landscape for spinal muscular atrophy (SMA), researchers from Australia have outlined ethical considerations stakeholders face when it comes to both the screening and treatment of the disease, including how severity of disease is taken into account.
Across these ethical considerations, the researchers emphasized the importance of collaborating with patients and their caregivers, including in decisions about treatment eligibility as additional longitudinal evidence becomes available for treatments like risdiplam (approved in 2020) and nusinersen (approved in 2016), both of which have shown improvements in motor function and survival.
“While new therapies for SMA are extremely welcome, the rapid pace of their development is generating ethical complexity for health professionals and families. The long-term effects and outcomes of novel therapies for SMA remain uncertain,” the study authors wrote in Australian Journal of General Practice. “While they may prevent further decline, disease-modifying therapies are not a cure for SMA, and children who commence treatment after symptom onset might continue to live with impairment. It is important to manage parental optimism and hope, and ensure that benefits are not overestimated while possible harms are underplayed.”
Access to these treatments also poses concerns, explained the researchers, citing restrictions related to age, treatment location, SMN2 copies, and disease progression. For example, patients who are presymptomatic with at least 3 copies of SMN2 are unable to be reimbursed for disease-modifying treatments.
In their paper, the researchers also pose ethical considerations for SMA prior to and immediately after birth. As with other genetic conditions, SMA is included in most commercial panels for reproductive carrier screening (RCS). If it’s determined that a child will likely have SMA, parents have the option for further interventions, including undergoing preimplantation genetic testing where they choose an embryo without 2 copies of the SMN1 pathogenic variant.
Prenatal diagnosis is also used to help a couple prepare for or avoid the birth of a child with SMA.
The researchers noted that although RCS gives parents the opportunity to make their own reproductive decisions, the process also carries ethical concerns, with the group recommending couples be referred to appropriate RCS providers who are available to provide counseling after testing.
“For SMA specifically, identifying carriers of a pathogenic variant in the SMN1 gene does not, on its own, predict the severity of SMA that a child may develop,” they explained. “A further consideration is the wider debate on the place of disability and difference in society. It has been argued that prenatal screening is unjustly discriminatory, particularly when there is variable presentation. Reasons include an implicit purpose of eradicating disability and diminishing diversity, thereby devaluing people living with genetic conditions such as SMA.”
With an emphasis placed on timely intervention, newborn screening (NBS) is recognized as another crucial opportunity for early detection of the disease, with countries worldwide implementing NBS programs.
However, similar to RCS, the screening method also comes with controversies, as in the case of a patient having more than 3 copies of SMN2, leaving questions of the severity of disease and uncertainty around when the patient will present with symptoms and how and when should intervention be initiated.
Newson AJ, Dive L, Cini J, Hurley E, Farrar MA. Ethical aspects of the changing landscape for spinal muscular atrophy management in Australia. Aust J Gen Pract. 2022;51(3):131-135. doi:10.31128/AJGP-06-21-6028