"In addition to its clinically-validated activity in a broad range of hematologic and solid tumor cancers, nuclear export protein Exportin 1, or XPO1, has also emerged as an attractive target for the treatment of neuro-inflammatory disorders such as traumatic brain injury," said
In an oral presentation titled "Functional and Imaging Studies of the Selective Inhibitor of Nuclear Export (SINE) Compound KPT-350 in a Clinically Relevant Murine Model of Traumatic Brain Injury (TBI)," Karyopharm researchers and collaborators presented data evaluating the efficacy of KPT-350 as a treatment for TBI in a murine model of closed head injury (CHI) and determined that orally administered KPT-350 improved functional outcomes, possibly by reducing cytotoxic intracellular edema.
Highlights of the data include:
- KPT-350 demonstrated improved long-term measures of physical and cognitive function relative to the vehicle or delayed treatment group.
- Mice that received KPT-350 two hours post-CHI recovered body weight more quickly and performed better in the Rotarod test of vestibulomotor function
- Diffusion tensor imaging studies demonstrated changes in the mean diffusivity index in several brain regions, suggesting that KPT-350 reduced cellular swelling versus vehicle
In an oral and poster presentation titled "Using the Selective Inhibitor of Nuclear Export (SINE) Compound KPT-350 to Reduce Cortical Circuit Hyperexcitability and Interneuron Cell Loss in the Controlled Cortical Impact (CCI) Model of Traumatic Brain Injury (TBI)," Karyopharm researchers and collaborators presented data evaluating the effects of orally administered KPT-350 on cortical network dysfunction in a murine model of TBI and determined that KPT-350 treatment protected mice from the damaging electrophysiological changes associated with CCI injury, suggesting a potential anti-epileptogenic effect.
Highlights of the data include:
- Following CCI-injury, brain tissues from mice treated with KPT-350 were free of seizure-associated activity, as compared with vehicle-treated mice, which showed high levels of such activity
- KPT-350 treatment normalized various measures known to correlate with aberrant brain function, such as coastline values and input-output response relationships, as compared with vehicle
KPT-350, an oral SINETM compound, is an investigational new drug application-ready oral compound with preclinical data supporting potential efficacy in a number of neurological, autoimmune and inflammatory conditions. XPO1 inhibition leads to potent, multifaceted inhibition of the inflammatory mediator nuclear factor kappa-light-chain-enhancer of activated B cells, or NF-kB, a protein that plays very important roles in many types of inflammation. KPT-350 has additional important activities such as activation of proteins leading to anti-oxidant and neuroprotective properties. Preclinical data, generated mainly by Karyopharm's academic collaborators, has shown efficacy of orally-administered KPT-350 in animal models of amyotrophic lateral sclerosis, or ALS, traumatic brain injury, or TBI, multiple sclerosis, or MS, systemic lupus erythematosus, or SLE, and rheumatoid arthritis, or RA.
This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding the therapeutic potential of and potential clinical development plans for Karyopharm's drug candidates, including the timing of initiation of certain trials and of the reporting of data from such trials. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from the company's current expectations. For example, there can be no guarantee that any of Karyopharm's SINE™ compounds, including KPT-350, or any other drug candidate that Karyopharm is developing will successfully complete necessary preclinical and clinical development phases or that development of any of Karyopharm's drug candidates will continue. Further, there can be no guarantee that any positive developments in Karyopharm's drug candidate portfolio will result in stock price appreciation. Management's expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the following: Karyopharm's results of clinical trials and preclinical studies, including subsequent analysis of existing data and new data received from ongoing and future studies; the content and timing of decisions made by the
Justin Renz(617) 658-0574 email@example.com Gina Nugent(617) 460-3579 firstname.lastname@example.org
Source: Karyopharm Therapeutics
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