Selecting the right candidate: Which disease-causing variants are eligible for N=1 ASOs?

September 18, 2023 12:30-1:30 pm US EST -

Individualized genetic treatments provide new opportunities for targeted therapies for rare disease patients. Unfortunately, not all individuals affected by a rare disease qualify for tailored N=1 approaches, and selecting those most likely to benefit is challenging. Patient identification can be divided into the evaluation of (i) the disease-causing variant, (ii) the disease, and (iii) the status of the affected individual.

Here, we present recommendations on evaluating the disease-causing variants of individuals affected by a rare disease for their amenability to N=1 treatment approaches using splice-switching antisense oligonucleotides. We illustrate that only a small percentage of variants qualify for these individualized treatments, and, hence, careful prioritization of genetic variants is a crucial step in patient identification. The selection criteria and framework have been established by members of the N1C Patient Identification group.

Marlen Lauffer, MD is a senior researcher at the Dutch Center for RNA Therapeutics (DCRT). She has a background in biochemistry, human molecular genetics, and medicine, and has been studying rare diseases in and outside of the wet lab for the past decade. Marlen is especially interested in rare neurological disorders manifesting in childhood, like neurodevelopmental disorders and childhood dementias. At the DCRT, Marlen is responsible for patient evaluation and selecting amenable genetic variants for N=1 treatments as well as overseeing the development and testing of antisense oligonucleotides in the wet lab. She is co-leading the N1C Patient Identification Group.