Hector Ribeiro Benatti, Rachel D Prestigiacomo, Toloo Taghian, Rachael Miller, Robert King, Matthew J Gounis, Ugur Celik, Stephanie Bertrand, Susan Tuominen, Lindsey Bierfeldt, Elizabeth Parsley, Jillian Gallagher, Erin F Hall, Abigail W McElroy, Miguel Sena-Esteves, Anastasia Khvorova, Neil Aronin, Heather L Gray-Edwards
Oligonucleotide therapeutics offer great promise in the treatment of previously untreatable neurodegenerative disorders; however, there are some challenges to overcome in pre-clinical studies. (1) They carry a well-established dose-related acute neurotoxicity at the time of administration. (2) Repeated administration into the cerebrospinal fluid may be required for long-term therapeutic effect. Modifying oligonucleotide formulation has been postulated to prevent acute toxicity, but a sensitive and quantitative way to track seizure activity in pre-clinical studies is lacking...
December 14, 2023: Molecular Therapy. Methods & Clinical Development