MRC Holland Announces Quick and Low-Cost Blood Test to Screen Newborns for SMA

José Lopes, PhD avatar

by José Lopes, PhD |

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MRC Holland has launched a newborn screening test, called SALSA MC002 SMA Newborn Screen, that uses a blood sample to detect a specific SMN1 gene alteration that underlies spinal muscular atrophy (SMA).

The first in the company’s SALSA Melt Assay product line, this assay can reliably, quickly and cost-effectively detect the presence or absence of SMN1 gene exon 7, while also indicating the SMN1:SMN2 ratio, MRC Holland states in a press release. Exons are the bits of DNA that contain the information to generate proteins.

SMA is caused by mutations in the SMN1 gene that affect production of the SMN protein, which is key to the survival and working of motor neurons – cells that control muscle contraction. Although SMN2, a copy gene, can also produce SMN, only 10% of the resulting protein is functional. Still, SMN2 influences the severity of SMA and is the target of therapies like Spinraza (nusinersen, by Biogen) and potential treatments like risdiplam (Roche, PTC Therapeutics).

In most populations, 95-98% of SMA cases results from complete loss of SMN1 exon 7, which makes its assessment a reliable and sensitive way to diagnose SMA.

Since the approval of Spinraza in 2016, other therapeutic approaches are advancing in development, including treatments targeting children who have not yet displayed SMA symptoms. For example, recent results have shown that presymptomatic treatment of 25 infants with Spinraza significantly delayed disease progression and enabled them to reach motor milestones otherwise not possible, including sitting without support and walking without assistance.

Novartis, with AveXis, is conducting the SPR1NT Phase 3 trial (NCT03505099) of its SMA gene therapy candidate AVXS-101 in pre-symptomatic infants with SMA  types 12 or 3, and Roche and PTC Therapeutics are planning to soon begin recruiting pre-symptomatic SMA type 1 infants to evaluate risdiplam’s safety and efficacy in a new trial called RAINBOWFISH.

An increased focus on newborn SMA screening is evident in the recent addition of the disorder to the Recommended Uniform Screening Panel for newborns in the U.S.

The low-cost – around $5 (4 euros) per sample – SALSA MC002 SMA Newborn Screen is the first newborn screening assay for SMA that is CE-marked, a European certification that guarantees compliance with relevant regulatory requirements for a proper and safe use – for in vitro diagnostic use.

It runs on standard equipment, does not require purification of DNA samples, and has a turnaround time from dried blood spot card punch to results of nearly four hours, MRC Holland reports. Of note, as SALSA MC002 SMA Newborn Screen only determines whether a sample has SMN1 gene exon 7 – not absolute copy numbers – and cannot identify carriers.

In comparison to assays based on a molecular biology technique called qPCR, the new assay is more robust and less sensitive to sample-to-sample contamination, a frequent issue in DNA sequencing that occurs when different samples are accidentally mixed, the company reports. It can be used with common DNA sequencing, cloning and quantification devices called thermocyclers and does not require additional software.

The Netherlands-based company focuses on the production of reliable assays for gene copy number and gene variant detection to be used in research and diagnostic settings.

It previously developed the Multiplex Ligation-dependent Probe Amplification (MLPA) assays, including several assays to detect SMA patients and carriers. According to MRC-Holland, MLPA is the gold standard for DNA copy number quantification and is used in both hereditary disorders and tumors.