golotimod and Disease-Models--Animal

To evaluate the efficacy of a novel immunomodulating peptide (SCV-07) in attenuating the course of radiation-induced mucositis in an established animal model of oral mucositis (OM).. In three separate experiments, golden Syrian hamsters received either an acute radiation challenge to the buccal mucosa of eight fractionated doses of 7.5 Gy of radiation over a 2-week-period, or a combination of acute radiation and cisplatin. In each experiment, animals were treated with varying doses or schedules of SCV-07 or placebo. OM was scored in a blinded fashion using digital images obtained during the experimental period.. We found that SCV-07 reduced the severity and duration of both acute and fractionated radiation-induced OM. Similarly, when radiation and chemotherapy were used to induce OM, treatment with SCV-07 significantly reduced the duration of ulcerative OM. The therapeutic benefit was dependent on both dose and schedule of administration.. Taken together, we found SCV-07 was able to modify the duration and severity of oral mucositis and was dependent on schedule and dose.

Topics: Animals; Antineoplastic Agents; Cisplatin; Cricetinae; Dipeptides; Disease Models, Animal; Dose Fractionation, Radiation; Dose-Response Relationship, Drug; Gingivitis, Necrotizing Ulcerative; Immunologic Factors; Male; Mesocricetus; Mouth Mucosa; Oral Ulcer; Placebos; Radiotherapy; Single-Blind Method; Stomatitis; Time Factors

Herpes simplex virus type 2 (HSV-2) infections produce a recurrent disease state associated with susceptibility to other pathogens, including human immunodeficiency virus (HIV), and cannot be cured by current therapeutic treatments. The HSV-2 epidemic must therefore be addressed by therapeutic strategies that reduce recurrent lesions and ideally lack the possibility for development of drug resistance. To this end, the therapeutic potential of SCV-07 (gamma-D-glutamyl-L-tryptophan), a synthetic dipeptide with potent immunomodulatory and antimicrobial activity, was studied in the guinea pig model of recurrent genital HSV-2. Initial evaluations showed that when delivered orally, but not subcutaneously, SCV-07 significantly reduced recurrent lesions. Oral dose ranging studies indicated that, of the tested amounts, 5microg/kg was optimal when delivered after an overnight fast. Interestingly, fasting induced a significant increase in recurrent lesions in vehicle-treated guinea pigs relative to non-fasted animals. Despite this increase, SCV-07 significantly reduced lesion formation in treated animals but showed no durability following cessation of treatment. In fact, this regimen of SCV-07 treatment produced statistically indistinguishable outcomes compared with those provided by topical aciclovir. These data illustrate that SCV-07 may provide an easily administered alternative or supplemental treatment option for genital HSV-2 recurrent disease.

Topics: Acyclovir; Animals; Antiviral Agents; Dipeptides; Disease Models, Animal; Drug Therapy, Combination; Female; Guinea Pigs; Herpes Genitalis; Herpesvirus 2, Human; Humans; Secondary Prevention; Treatment Outcome