New chemical designs for gene-silencing medicines that reach the brain and spinal cord
Expanding the Chemical Diversity of Therapeutic Oligonucleotides
Developing new chemical versions of gene-silencing medicines to reach the brain and spinal cord for people with ALS and similar genetic neurodegenerative diseases.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Univ of Massachusetts Med Sch Worcester NIH-funded |
| Lab location | 1 site (Worcester, United States) |
| Project ID | NIH-11306598 on NIH RePORTER |
What this research studies
This project creates modified gene-silencing molecules (like siRNA and antisense oligonucleotides) designed to be more stable and to spread evenly through the brain and spinal cord. Scientists attach specially designed chemical groups (multivalent structures and lipophilic tags) and test delivery by infusing these compounds into the cerebrospinal fluid of animals including rodents, sheep, and nonhuman primates to measure distribution and safety. The team is also developing allele-selective and intra-nuclear targeting so the molecules can silence harmful gene copies while sparing normal ones. If the chemistry and delivery work well in these models, the work would support moving these therapies toward human clinical testing for ALS and related disorders.
Who could benefit from this research
Good fit: People with ALS or other genetically-defined neurodegenerative diseases caused by known harmful gene variants would be the likely candidates for later clinical trials of these therapies.
Not a fit: People whose disease is not driven by a specific gene mutation, who cannot undergo CSF-based treatment, or who have very advanced disease may not benefit from these approaches.
Why it matters
Potential benefit: Could enable gene-silencing drugs that safely and evenly reach the brain and spinal cord to lower toxic gene products in ALS and related disorders.
How similar studies have performed: Antisense and siRNA therapies delivered into the spinal fluid have worked in conditions like spinal muscular atrophy and in early ALS trials, but these specific multivalent chemistries and goals for broad uniform CNS distribution are newer.
Where this research is happening
Worcester, United States
- Univ of Massachusetts Med Sch Worcester — Worcester, United States (Active)
Researchers
- Principal investigator: Khvorova, Anastasia — Univ of Massachusetts Med Sch Worcester
- Study coordinator: Khvorova, Anastasia
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page below.