Clinical and serological outcomes in patients treated with oral doxycycline for early neurosyphilis.

OBJECTIVES: Penicillin-based antibiotic treatment for syphilis infection with CNS involvement (early neurosyphilis) is not always a suitable treatment option. We compared outcomes of patients diagnosed with early neurosyphilis and treated with doxycycline or procaine G penicillin. METHODS: Serological and clinical outcomes were analysed in patients diagnosed with early neurosyphilis between January 2015 and October 2019 at 56 Dean Street, a combined sexual health and HIV service based in London, UK. Acute onset of CNS, ocular and/or otic symptomatology and a documented seroconverting syphilis serology or a >4-fold increase in rapid plasma reagin ('RPR)' test titre within the previous 12 months were criteria used to define a case. Mann-Whitney U-test and χ2 tests were used to test distributions between baseline characteristics and outcomes according to treatment administered. RESULTS: Eighty-seven patients were included: median age = 35 years (IQR = 31-45), 98% MSM, 79% white ethnicity, 53% HIV-1 positive and 40% previously diagnosed with syphilis at any stage. They were treated exclusively with either intramuscular (IM) procaine G penicillin (71%) or oral doxycycline (18%). Patients received doxycycline treatment over a penicillin-based regimen due to IM treatment declined (31%), inability to attend for IM injections (31%) or penicillin allergy (19%). Serological response was achieved by all patients; 91% reported full symptom resolution at 30 days from end of treatment. Similar rates of clinical and serological response and seroreversion were observed in the groups treated with procaine G penicillin versus doxycycline. CONCLUSIONS: The clinical and serological outcomes seen with penicillin-based versus doxycycline treatments were similar. A randomized controlled trial is needed to establish the effectiveness of doxycycline in the treatment of early neurosyphilis.

Novel lipoproteoplex delivers Keap1 siRNA based gene therapy to accelerate diabetic wound healing.

Therapeutics utilizing siRNA are currently limited by the availability of safe and effective delivery systems. Cutaneous diseases, specifically ones with significant genetic components are ideal candidates for topical siRNA based therapy but the anatomical structure of skin presents a considerable hurdle. Here, we optimized a novel liposome and protein hybrid nanoparticle delivery system for the topical treatment of diabetic wounds with severe oxidative stress. We utilized a cationic lipid nanoparticle (CLN) composed of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and the edge activator sodium cholate (NaChol), in a 6:1 ratio of DOTAP:NaChol (DNC). Addition of a cationic engineered supercharged coiled-coil protein (CSP) in a 10:1:1 ratio of DNC:CSP:siRNA produced a stable lipoproteoplex (LPP) nanoparticle, with optimal siRNA complexation, minimal cytotoxicity, and increased transfection efficacy. In a humanized murine diabetic wound healing model, our optimized LPP formulation successfully delivered siRNA targeted against Keap1, key repressor of Nrf2 which is a central regulator of redox mechanisms. Application of LPP complexing siKeap1 restored Nrf2 antioxidant function, accelerated diabetic tissue regeneration, and augmented reduction-oxidation homeostasis in the wound environment. Our topical LPP delivery system can readily be translated into clinical use for the treatment of diabetic wounds and can be extended to other cutaneous diseases with genetic components.