Biogen added a new ALS drug candidate to its portfolio this month. The strategy, developed by Karyopharm Therapeutics in Newton, Massachusetts, aims to protect motor neurons in ALS by blocking nuclear export. The approach, which targets the exportin Xpo1/CRM1, may reduce motor neuron toxicity in ALS in part, by helping keep TDP-43 from building up in the cytoplasm (see January 2018 news).
The small molecule, known as KPT-350, is one of a group of compounds to be further developed by Biogen in Cambridge, Massachussetts as a potential therapy for neurological diseases including ALS. The strategy is at the preclinical stage.
The approach builds on previous preclinical studies led by Johns Hopkins University School of Medicine’s Jeffrey Rothstein and Thomas Lloyd, which suggest that this strategy may help reduce motor neuron loss in C9orf72 ALS/FTD and Huntington’s disease (Grima et al., 2017; Tamir et al, 2017).
The $217M USD milestone-based licensing deal, announced by Karyopharm Therapeutics on Jan 25, is announced less than a month after Mayo Clinic’s Wilfried Rossoll and colleagues in Jacksonville, Florida reported that cytoplasmic TDP-43 may disrupt nucleocytoplasmic transport of key proteins and RNAs by sequestering key structural components of nuclear pores (see January 2018 news; Chou et al., 2018). TDP-43 aggregates are estimated to clutter the cytoplasm of motor neurons in more than 95% of cases of ALS (Neumann et al., 2006).
To learn more about how a nuclear traffic tie-up may contribute to ALS, check out TDP-43 Snarls Nuclear Traffic.
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