Although this is just a single case so far, this observation suggests that Spinraza could be beneficial to other body systems beyond motor neurons, a theory that still needs to be confirmed in other treated patients. This also may add insight on the therapy’s mode of action and the role of the SMN2 gene in less common SMA symptoms such as injury to the skin.
The study, “Resolution of skin necrosis after nusinersen treatment in an infant with spinal muscular atrophy,” was published in the journal Muscle & Nerve.
Skin necrosis is thought to stem from problems in multiple organs, including poor blood supply to tissues and a malfunction of the autonomic nervous system. This system regulates the function of internal organs, including blood vessels, stomach, intestine, liver, kidneys, and lungs, that work automatically to control blood pressure and breathing rate, for example.
The child was diagnosed immediately after birth, showing severe hypotonia (lack of muscle tone) and lack of crying.
At 4 months old, she was seen in the emergency room due to necrosis, or dying tissue, in her toes. Necrosis is a type of cell or tissue death resulting from severe injury or disease, including insufficient blood supply, bacterial infection, traumatic injury, or abnormally high body temperature.
Over the next month after that visit, the infant’s fingertips also became extensively necrotic. In a few days, the lesions had spread into deep necrotic areas of dying tissue, which eventually led to the loss of one of her toes.
A diagnosis of epidermolysis bullosa, a rare condition marked by skin blisters, was discarded given the clinical signs and the lack of response to an antibacterial cream commonly used for this disease.
At 7.6 months old, she began treatment with Spinraza, which increases the ability of the SMN2 gene to produce the full-length SMN protein. She received her first intrathecal infusion of 10.8 mg, followed by another dose at days 15 and 30. During Spinraza therapy, her wound care protocol remained the same as before.
When admitted on day 60 for her Spinraza dose, a clinical evaluation showed that the skin lesions were healing, and the damaged regions were being replaced by scar tissue. In follow-up observations at nine months, doctors confirmed that all the lesions had been cured. Over that time, no changes in motor function were observed. The infant remained on treatment with Spinraza.
The researchers emphasize that these findings should be interpreted with caution since this was a single case, but they also say these results may point to a beneficial effect of Spinraza beyond motor neurons, particularly in peripheral tissues such as the skin.
“We can hypothesize that skin rescue was multifactorial and nusinersen [Spinraza] may have contributed to resolve lesions more rapidly than what was occurring prior to treatment,” the researchers said.
“As treatment continues in this and other children it will be interesting to see if other patients with skin lesions have a similar response, as this will contribute to a better understanding of the mode of action of [Spinraza] and of the role of SMN2 regulation in SMA beyond motor neurons,” they concluded.