We’re thrilled to tell you about a study funded by the A-T Children’s Project and conducted by Charles River Laboratories which has provided new insights into potential treatments for ataxia-telangiectasia (A-T). While still in the early stages, the study identified eight existing drugs—already approved for other diseases or in advanced testing phases—that may correct biological pathways crucial for improving the repair of damaged DNA in A-T. Because these drugs are already well-studied for other conditions, researchers have a head start in understanding their potential. Please keep in mind, however, that these drugs have not been tested for safety or effectiveness in A-T yet, and so they should not be tried by anyone with A-T at this time.How Was the Study Conducted?
The process began with the development of a specialized test or “assay” to measure a particular way that cells respond to DNA damage (by activating a protein called Chk2). A combination of liquid dispensers, microplate readers, robotic plate handlers, high content imaging machines, cell culture systems and data analysis platforms was then assembled to create a high-throughput, automated pipeline.
Next, after performing a small pilot study, scientists applied this system to cells donated by individuals with A-T and screened about 6,000 compounds from drug libraries – collections of medications already approved for other uses or in late stages of clinical development. Drugs from the Prestwick and Selleck Chem FDA libraries, which include medications with well-known safety records, were screened first. Next, the search was expanded to a larger collection called the SPECS library, containing more experimental compounds.
What Did We Find?
From more than one hundred initial candidates, researchers narrowed the list to eight drugs that most effectively restored the response of A-T cells to DNA damage in the assay:
- Benzydamine Hydrochloride: A pain reliever and anti-inflammatory that may support cellular repair by reducing inflammation.
- Dimethisoquin Hydrochloride: A topical anesthetic that might improve cell stress responses and nerve function.
- Mepazine: A drug that influences immune activity and could help stabilize DNA repair mechanisms.
- Domperidone: A medication that interacts with dopamine receptors and might support brain signaling and movement.
- Carbetapentane Citrate: Traditionally used to suppress coughs, it may also reduce oxidative stress and inflammation.
- Dicyclomine HCl: Often used for digestive issues, this drug could ease cell stress and improve movement by blocking certain overactive neurotransmitters.
- 3-Alpha-Bis-(4-Fluorophenyl)-Methoxytropane: A drug that inhibits dopamine uptake, potentially enhancing brain function and stabilizing dopamine levels.
- Detropine: A histamine blocker that may create healthier environments for brain cells by reducing inflammation.
Why Does This Matter?
The biological commonalities shared by these drugs suggest that targeting processes like inflammation, oxidative stress, and a natural cell-cleaning process called autophagy could address some of the challenges caused by A-T. Autophagy helps cells clear out damaged components and recycle them to maintain health. By understanding how these drugs enhance autophagy and other pathways, researchers hope to develop strategies to improve movement, brain function, and overall health in individuals with A-T. It’s important to note, however, that these drug screens were not performed in brain cells—so further research is needed to confirm if the same effects apply to brain function.
What’s Next?
The next steps will involve working with A-T specialists and drug development experts to evaluate these findings further. Future research will focus on validating the drugs in preclinical studies, understanding their effects on brain cells, and exploring how they might work together with other treatments. These discoveries mark an exciting starting point in the search for effective A-T therapies, separate from other strategies being explored concurrently, such as gene therapy.
Thank You to Our Supporters
This progress wouldn’t be possible without a perfectly timed introduction to CRL provided by the family of Connor Graban who has A-T and the generosity of numerous donors and fundraisers. We look forward to keeping you updated as this research moves forward.
Learn more about the specific methods and detailed findings from this study:
