Nusinersen
Nusinersen Uses, Dosage, Side Effects, Food Interaction and all others data.
An antisense oligonucleotide that induces survival motor neuron (SMN) protein expression, it was approved by the U.S. FDA in December, 2016 as Spinraza for the treatment of children and adults with spinal muscular atrophy (SMA). It is adminstrated as direct intrathecal injection.
Autopsy samples from patients (n=3) had higher levels of SMN2 messenger ribonucleic acid (mRNA) containing exon 7 in the thoracic spinal cord compared to untreated SMA infants.Cardiac Electrophysiology: In 121 patients with spinal muscular atrophy who received either nusinersen or sham-control, QTcF values >500 ms and change from baseline values >60 ms were observed in 5% of patients receiving nusinersen. Compared to the sham-control, there was no increase in the incidence of cardiac adverse reactions associated with delayed ventricular repolarization in patients treated with nusinersen.
| Trade Name | Nusinersen |
| Availability | Prescription only |
| Generic | Nusinersen |
| Nusinersen Other Names | Nusinersen |
| Related Drugs | Spinraza, Evrysdi, Zolgensma, risdiplam |
| Weight | 12mg/5ml |
| Type | Intrathecal, Intrathecal Solution, Injection |
| Protein binding | CSF: < 25% Plasma: >94% |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | United States |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Nusinersen is a medication used to treat spinal muscular atrophy.
Indicated for the treatment of spinal muscular atrophy (SMA) in pediatric and adult patients.
Nusinersen is also used to associated treatment for these conditions: Spinal Muscular Atrophy (SMA)
How Nusinersen works
Nusinersen is a survival motor neuron-2 (SMN2)-directed antisense oligonucleotide (ASO) designed to treat SMA caused by mutations in chromosome 5q that lead to SMN protein deficiency. Using in vitro assays and studies in transgenic animal models of SMA, nusinersen was shown to increase exon 7 inclusion in SMN2 messenger ribonucleic acid (mRNA) transcripts and production of full-length SMN protein. Nusinersen acts to replace the SMN protein deficit which causes SMA, by increasing the splicing efficiency of the SMN2 pre- mRNA. More specifically, nusinersen in an 18-mer 2’-MOE phosphorothioate antisense oligonucleotide that acts as a splice-altering oligonucleotide. Nusinersen was designed to pair with a specific target sequence on the SMN2 pre-mRNA to displace heterogeneous ribonucleoproteins (hnRNPs) at the intronic splice silencing site-1 (ISS-1) between exons 7 and 8 to allow for more complete translation of SMN protein from the paralogous gene SMN2. Further reinforcing this concept, SMA phenotype is closely tied to SMN2 copy number. SMN2 serves to produce SMN protein, however at a greatly reduced rate because of differential splicing caused by the binding of the hnRNPs at the ISS-1.
Toxicity
Single injection to adult monkeys produced apparent acute neurological impairment.
Food Interaction
No interactions found.Nusinersen Disease Interaction
Volume of Distribution
CSF: 0.4 L Plasma: 29 L
Elimination Route
Intrathecal injection of nusinersen into the cerebrospinal fluid (CSF) allows it to be distributed from the CSF to the target central nervous system (CNS) tissues. Following intrathecal administration, trough plasma concentrations of nusinersen were relatively low, compared to the trough CSF concentration. Median plasma Tmax values ranged from 1.7 to 6.0 hours. Mean plasma Cmax and AUC values increased approximately dose-proportionally up to a dose of 12 mg.
Half Life
The mean terminal elimination half-life is estimated to be 135 to 177 days in CSF, and 63 to 87 days in plasma .
Clearance
Slow clearance is observed
Elimination Route
Excreted by the kidney as chain-shortened oligonucleotides, which are not considered pharmacologically active.
Innovators Monograph
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