New lab test may help in studying effects of Spinraza treatment

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by Lindsey Shapiro PhD |

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A scientist works in a laboratory with a dropper and petri dishes, alongside a rack with four full vials.

Researchers have developed a new laboratory technique for measuring levels of Spinraza (nusinersen), an approved treatment for spinal muscular atrophy (SMA), in biological fluids.

The test is expected to help overcome some limitations of other approaches now in use, and may therefore aid scientists and physicians when studying the effects of the therapy in the body.

“We have developed a rapid, simple and high-throughput analytical strategy for the detection of nusinersen sodium [Spinraza] in human serum [blood] samples,” the researchers wrote, adding that the test was accurate and precise, and allowed for clinical monitoring of Spinraza treatment.

The study, “A sensitive analytical strategy of oligonucleotide functionalized fluorescent probes for detection of nusinersen sodium in human serum,” was published in Talanta.

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A researcher uses a microscope in a lab alongside a rack of vials and a full beaker.

Protein a potential biomarker of Spinraza treatment responses

New methods needed to better assess levels of Spinraza treatment in body

In SMA, Spinraza works to increase levels of the SMN protein that patients lack due to mutations in the SMN1 gene. It’s given via injections directly into the spinal canal — known as intrathecal administration — once every four months.

Another gene called SMN2 can also make SMN protein, albeit less effectively than SMN1. Spinraza essentially works to boost SMN2’s production of SMN so as to better compensate for the genetic deficiency and ease SMA symptoms.

The reason SMN2 less effectively produces SMN is because of certain changes in its messenger RNA (mRNA), a kind of intermediate template molecule that’s formed when converting the information in DNA to a functional protein.

Spinraza contains what’s called an antisense oligonucleotide, or ASO, which binds to the SMN2 mRNA and corrects the change that normally prevents it from making enough SMN protein. Oligonucleotides are made up of small strands of genetic material (DNA or RNA).

One way that scientists monitor a treatment’s pharmacological properties and clinical effects is by measuring its levels in biological fluids, namely the blood or the cerebrospinal fluid that surrounds the brain and spinal cord.

However, oligonucleotides like Spinraza have a short half-life, meaning they break down quickly, and are prone to accumulating in the liver and kidneys. As such, Spinraza’s levels are usually very low when measured in these body fluids, and scientists face a number of challenges when trying to detect it with available methods.

Now, a team of researchers from China proposed a new strategy for the sensitive detection of Spinraza in human blood samples.

Ultimately, the approach is designed in such a way that when Spinraza is present in a blood sample, it binds to a red fluorescent probe that can be detected with laboratory techniques. This strategy also uses other molecules intended to help amplify the signal and make it easier to detect.

The intensity of that fluorescent signal reflects how much Spinraza is present, with more fluorescence corresponding to a higher concentration of the SMA treatment.

[Technique proved a] rapid, accurate, and sensitive method of nusinersen sodium [Spinraza] detection in biological samples.

Through a series of optimization experiments, the scientists characterized and validated their approach, showing that the technique was a “rapid, accurate, and sensitive method of nusinersen sodium detection in biological samples,” they wrote.

The analysis took less than 30 minutes, and eliminated several lengthy steps that other analytical approaches require, the researchers reported. According to the team, it will help in evaluating the pharmacokinetics — the study of how the body interacts with a treatment for the entire time of exposure — of Spinraza.

“The established method provides technical support for the pharmacokinetic and clinical study of nusinersen sodium and antisense oligonucleotides,” the team concluded.

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