NIH identifies antisense oligos to treat progeria; plus epigenetic gene therapies for chronic pain and Cend’s pancreatic cancer therapy

Antisense oligonucleotides to treat progeria
Two NIH teams, one led by NIH director Francis Collins, discovered antisense oligonucleotides (ASOs) against the LMNA gene to treat Hutchinson-Gilford progeria syndrome (HGPS). The disorder is caused by progerin, a toxic protein encoded by mutated LMNA. A group led by Tom Misteli, cell biology of genomes group head, identified in a screen lipid-conjugated ASO that extended lifespan in a mouse model of HGPS. Collins’ group created an antisense peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO), dubbed SRP-2001, that decreased progerin transcript levels in patient fibroblasts. In a mouse model of HGPS, life-long treatment with IV SRP-2001 beginning at age three weeks extended life and prevented vascular smooth muscle cell loss in large arteries. Both studies were published in Nature Medicine.

Epigenetic sodium channel repression for chronic pain
University of California San Diego scientists including Navega Therapeutics Inc. co-founders presented in Science Translational Medicine adeno-associated viral (AAV) vector-delivered epigenetic therapies to treat chronic pain. The AAVs delivered CRISPR-dCas9 or zinc finger constructs that repress sodium channel Nav1.7. In models of neuropathic pain including a chemotherapy-triggered model, administration into the spinal canal decreased thermal hyperalgesia and tactile allodynia. Navega is developing gene therapies for chronic pain as non-addictive, long-lasting alternatives to opioids...