The associate neurologist-in-chief at Boston Children’s Hospital discussed the 4-copy conundrum and whether treatment decisions differ based on SMN2 copies for patients with spinal muscular atrophy. [WATCH TIME: 2 minutes]
WATCH TIME: 2 minutes
"There was a committee convened by Cure SMA which has met a few times. During the last meeting, we voted in favor of treating babies with 4 copies of SMN2. That was published in a journal, but in spite of that, some insurance companies don’t even know about it or won’t take it into consideration."
Spinal muscular atrophy (SMA), a devastating neuromuscular disorder, is caused by low levels of the survival motor neuron (SMN) protein due to inactivating mutations in the encoding gene SMN1. A second duplicated gene, SMN2, produces little but sufficient functional protein for survival. Each of the 3 approved therapies for SMA increases the amount of full-length SMN protein; however, nusinersen (Spinraza; Biogen) and risdiplam (Evrysdi; Genentech) operate from SMN2, whereas AVXS-101 (Zolgensma; Novartis) produces the protein from SMN1.
AVXS-101, the only gene replacement therapy on the market, is approved for patients with type 1 SMA who have up to 3 SMN2 copies. The number of SMN2 copes was the first SMA modifier identified and is still the strongest known; however, the SMN2-copy number does not allow to precisely predict the course of the disease in a given individual. Clinicians within the space, including Basil Darras, MD, are still learning how to approach and treat infants with 4 copies of SMN2, otherwise known as the four-copy conundrum.
In a presentation given at the 2022 Cure SMA Clinical & Scientific Conference, June 15-17, in Anaheim, California, Darras provided an overview on the lingering questions with treating presymptomatic SMA and choosing the appropriate treatments. Darras, associate neurologist-in-chief at Boston Children’s Hospital, provided background on how the clinical community has approached infants with 4 SMN2 copies and whether treatment strategies change based on copy number.