A new Boston-area startup is setting its sights on neurodegenerative diseases including ALS and frontotemporal dementia (FTD). The early-stage biotech company, known as Skyhawk Therapeutics, aims to treat ALS and FTD by correcting RNA splicing defects that may underlie at least some forms of the disease (for example, see March 2011 news; Polymenidou et al., 2011).
The approach, being developed in collaboration with Celgene in Summit, New Jersey, uses RNA-targeted small molecules to reduce exon skipping during the splicing process. Skyhawk Therapeutics is currently using this strategy to develop therapies for certain forms of cancer including tumors in the brain and the pancreas.
The partnership, announced on June 26, enables Celgene to license up to 5 potential therapies for ALS, Huntington’s disease and other neurological disorders. The $60M USD licensing deal comes at the heels of a recent study, led by Pietro Fratta at the University College London in England, which found that ALS-linked changes in TDP-43 leads to exon skipping during the splicing of transcripts of at least some genes (see May 2018 news; Fratta et al., 2018).
To learn more about the emerging role of RNA mis-splicing in ALS, check out TDP-43 Skips Out On Some Exons in ALS.
Fratta P, Sivakumar P, Humphrey J, Lo K, Ricketts T, Oliveira H, Brito-Armas JM, Kalmar B, Ule A, Yu Y, Birsa N, Bodo C, Collins T, Conicella AE, Mejia Maza A, Marrero-Gagliardi A, Stewart M, Mianne J, Corrochano S, Emmett W, Codner G, Groves M, Fukumura R, Gondo Y, Lythgoe M, Pauws E, Peskett E, Stanier P, Teboul L, Hallegger M, Calvo A, Chiò A, Isaacs AM, Fawzi NL, Wang E, Housman DE, Baralle F, Greensmith L, Buratti E, Plagnol V, Fisher EM, Acevedo-Arozena A. Mice with endogenous TDP-43 mutations exhibit gain of splicing function and characteristics of amyotrophic lateral sclerosis. EMBO J. 2018 Jun 1;37(11). pii: e98684. [PubMed].
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Ling JP, Pletnikova O, Troncoso JC, Wong PC. TDP-43 repression of nonconserved cryptic exons is compromised in ALS-FTD. Science. 2015 Aug 7;349(6248):650-5. [PubMed].