Delivering RNA-Targeted
Medicines
Delivering RNA-Targeted
Medicines
Preliminary research has demonstrated that investigational RNA-targeted medicines can penetrate tissues throughout the central nervous system (CNS) and are active across a wide range of cell types in the CNS.1-6
These findings offer the opportunity to develop RNA-targeted medicines for many types of neurologic diseases.1
Investigational RNA-targeted medicines can be delivered to the spinal cord and deep regions within the brain, including the hippocampus, pons, and amygdala.1-4
Dose Response and Accumulation of
Investigational RTMs in Mouse CNS Tissue1,a,b
aEach of the symbols (ie, circle, square, diamond, triangle) represents data from a single mouse at the dose plotted. bRTM used in the study targets Malat1 RNA.
CNS, central nervous system; PBS, phosphate-buffered saline; RTID, RNA-targeted investigational drug; RTM, RNA-targeted medicine.
Broad distribution of investigational RTMs and their activity in different brain structures and the spinal cord potentially offers the opportunity to develop these therapeutics for many types of neurological diseases that originate in the spinal cord and deep within the CNS.
Research in animal models has shown investigational RNA-targeted medicines are active in neurons, microglia, astrocytes, and oligodendrocytes.1-4
Dose-Dependent Reduction of mRNA With Investigational RTMs in All Four Major CNS Cell Types in Rodents1,a
aRTM used in the study targets Malat1 RNA.
CNS, central nervous system; ED50, effective dose; mRNA, messenger RNA; PBS, phosphate-buffered saline; RTM, RNA-targeted medicine.
Investigational RTMs can target the major cell types throughout the CNS, including neurons, oligodendrocytes, astrocytes, and microglia.
In human patients, investigational RNA-targeted medicines have been shown to distribute within the CNS.7
To see how this technology functions in the CNS, please watch the video below:
Learn more about Ionis’ approach to screening investigational RNA-targeted medicines and its pipeline candidates.
References
- Jafar-Nejad P, Powers B, Soriano A, et al. The atlas of RNase H antisense oligonucleotide distribution and activity in the CNS of rodents and non-human primates following central administration. Nucleic Acids Res. 2021;49(2):657-673.
- Korobeynikov VA, Lyashchenko AK, Blanco-Redondo B, Jafar-Nejad P, Shneider NA. Antisense oligonucleotide silencing of FUS expression as a therapeutic approach in amyotrophic lateral sclerosis. Nat Med. 2022;28(1):104-116.
- Mazur C, Powers B, Zasadny K, et al. Brain pharmacology of intrathecal antisense oligonucleotides revealed through multimodal imaging. JCI Insight. 2019;4(20):e129240.
- Mortberg MA, Gentile JE, Nadaf NM, et al. A single-cell map of antisense oligonucleotide activity in the brain. Nucleic Acids Res. 2023;51(14):7109-7124.
- Edwards AL, Collins JA, Junge C, et al. Exploratory tau biomarker results from a multiple ascending-dose study of BIIB080 in Alzheimer disease: a randomized clinical trial. JAMA Neurol. 2023;80(12):1344-1352.
- Finkel RS, Chiriboga CA, Vajsar J, et al. Treatment of infantile-onset spinal muscular atrophy with nusinersen: a phase 2, open-label, dose-escalation study. Lancet. 2016;388(10063):3017-3026.
- Bennett CF, Krainer AR, Cleveland DW. Antisense oligonucleotide therapies for neurodegenerative diseases. Annu Rev Neurosci. 2019;42:385-406.
