Harman Patil (Editor)

Miravirsen

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Covid-19
ATC code  none
Synonyms  SPC3649
PubChem CID  56843415
Legal status  Investigational
CAS Number  1072874-90-8
Miravirsen Antiviral Proof of Concept Study of Miravirsen an
Routes of administration  Intravenous or subcutaneous injection

Miravirsen (INN; codenamed SPC3649) is an experimental drug for the treatment of hepatitis C, being developed by Santaris Pharma.

Contents

Miravirsen

Mechanism of action

Miravirsen FINAL RESULTS Randomized Doubleblind Placebocontrolled Safety

Miravirsen is a short modified RNA molecule that is applied by intravenous or subcutaneous injection. It reaches the liver and binds to the human microRNA called miR-122; this mechanism makes it an antisense RNA. Miravirsen can also bind to the precursors of miR-122 with nanomolar affinity, inhibiting its biogenesis. The hepatitis C virus needs miR-122 to multiply, but cannot utilise it if bound by miravirsen.

Potential side effects

Miravirsen Closing Summary by JeanMichel Pawlotsky New HCV Drug Development

As miR-122 has tumour protective properties in liver cells, concerns about a possible risk of hepatic cancer have been voiced. The drug did not induce liver toxicity in non-human primates, nor in a human study.

Chemical properties

Miravirsen httpsuploadwikimediaorgwikipediacommonsthu

Miravirsen is a modified oligonucleotide consisting of a chain of 15 nucleotides, the base sequence of which is designed to selectively bind to miR-122. Seven of the 15 sugar units are desoxyriboses, and the other eight are riboses with an additional bridge between the 2' oxygen and the 4' carbon atoms; this makes the molecule a locked nucleic acid. Furthermore, the phosphate units have been replaced by thiophosphates.

The complete base sequence is

mC*-dC-A*-dT-dT-G*-mU*-dC-dA-mC*-dA-mC*-dT-mC*-mC* [d = 2'-deoxy, * = 2'-O,4'-C-methylene, i.e. bridged or "locked" sugar]

with 3'→5' thiophosphate linkages.

Research

Miravirsen Treating hepatitis C by blocking a cellular microRNA

Miravirsen reduced HCV viremia in a small-scale trial in chimpanzees and was found to be safe in a clinical trial in 27 humans over eight to eleven weeks.

Miravirsen Treatment of HCV Infection by Targeting MicroRNA NEJM

The drug underwent a Phase IIa trial in which patients were randomly assigned to placebo groups or one of the three multiple ascending dose groups (3 mg/kg, 5 mg/kg, 7 mg/kg of miravirsen). The naïve patients were given 5 weekly doses of miravirsen via subcutaneous injection for four weeks, and 4 out of 9 patients receiving the highest dose (7 mg/kg) exhibited significant decrease in hepatitis C virus RNA (p<0.001). The result was sustained even 10 weeks after the last miravirsen administration.

References

Miravirsen Wikipedia


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