Isis Pharmaceuticals Inc. has teamed up with a trio of academic groups to develop
antisense therapeutics for the largest subset of patients with amyotrophic
lateral sclerosis,1-3 and all three teams have converged on a common
mechanism of neurotoxicity caused by carrying hexanucleotide repeat expansions
in the C9orf72
gene. Antisense oligonucleotides targeting the repeats decreased the toxicity in
vitro. The teams now need to determine whether the reduced toxicity
correlates with decreased neurodegeneration in patients.
Bryan Traynor, investigator and chief
of the neuromuscular disease research unit at the National Institute of Aging
and an author on the Neuron paper, told SciBX, "It has just
been two years since the C9orf72 gene was published. We have been able
to develop the oligonucleotides so quickly that the animal models for this
genetic form of the disease do not exist yet."
Martz, L. SciBX 6(43); doi:10.1038/scibx.2013.1210 Published online
Nov. 7, 2013
1. Sareen, D. et al.
Sci. Transl. Med.; published online Oct. 23, 2013;
doi:10.1126/scitranslmed.3007529 Contact: Robert H. Baloh, Cedars-Sinai
Medical Center, Los Angeles, Calif. e-mail: firstname.lastname@example.org
2. Donnelly, C.J. et
al. Neuron; published online Oct. 16, 2013;
doi:10.1016/j.neuron.2013.10.015 Contact: Jeffrey D. Rothstein, The
Johns Hopkins University School of Medicine, Baltimore, Md. e-mail: email@example.com
Contact: Rita Sattler, same affiliation as above e-mail: firstname.lastname@example.org
3. Lagier-Tourenne, C. et
al. Proc. Natl. Acad. Sci. USA; published online Oct. 28, 2013;
doi:10.1073/pnas.1318835110 Contact: John Ravits, University of
California, San Diego, La Jolla, Calif. e-mail: email@example.com Contact: Don
W. Cleveland, same affiliation as above e-mail: firstname.lastname@example.org
4. DeJesus-Hernandez, M.
et al. Neuron 72, 245-256 (2011)
5. Renton, A.E. et al.
Neuron 72, 257-268 (2011)
6. Rosen, D.R. et al.
Nature 362, 59-62 (1993)
7. Deng, H.X. et al
Science 261, 1047-1051 (1993)
Biogen Idec Inc. (NASDAQ:BIIB), Weston, Mass.
Catholic University Leuven, Leuven, Belgium
Cedars-Sinai Medical Center, Los Angeles, Calif.
CuroNZ Ltd., Auckland, New Zealand
Isis Pharmaceuticals Inc. (NASDAQ:ISIS), Carlsbad, Calif.
The Johns Hopkins University School of Medicine, Baltimore, Md.
Ludwig Institute for Cancer Research Ltd., La Jolla, Calif.
Mayo Clinic, Jacksonville, Fla.
National Institute on Aging, Bethesda, Md.
University of California, Los Angeles, Calif.
University of California, San Diego, La Jolla, Calif.
University of Helsinki Helsinki,
University in St. Louis School of Medicine, St. Louis, Mo.