On October 24, 2018, CMI hosted a seminar given by Dr. Ethan Perlstein, CEO of Perlara. Perlara’s mission, according to their website https://www.perlara.com/about-us/, is “to accelerate the discovery of cures for rare genetic diseases and uncover underlying mechanisms that enable the development of treatments that work across a range of diseases and individuals.” Dr. Perlstein presented a seminar entitled, Model Organisms for n-of-1 Drug Discovery.
Conventional drug discovery involves human cell-based phenotypic screens or human protein target-based (often in silico-assisted) screens followed by validation in mice. While model organisms routinely identify and elucidate fundamental principles and mechanisms in biology, invertebrates are absent from or systematically under-utilized in academic and biopharma drug screening, especially for the 3,000+ rare monogenic diseases. Lysosomal storage diseases and congenital disorders of glycosylation are ideal for disease modeling in invertebrates because causal genes, regulatory pathways and pathophysiology are well conserved. Here we describe CRISPR-edited yeast, nematode, fly “patient avatars” of N-glycanase 1 Deficiency (NGLY1), Phosphomannomutase 2 Deficiency (PMM2-CDG), Niemann-Pick Type C (NPC) and Niemann-Pick Type A(NPA)/Acid Sphingomyelinase Deficiency (ASMD) for use in natural history and biomarker discovery studies, as well as high-throughput whole-animal drug repurposing and drug discovery.
Special thank you for the lunch hosted by Dr. Sean Ekins and Dr. Maggie Hupcey of Collaborations Pharmaceuticals, Inc.