"While efforts to develop antiviral therapies are important, provision of high-quality supportive care that includes diligent fluid and electrolyte repletion is fundamental to treating patients infected with Ebola virus," Dr. West said. "Based on the available evidence to date, these supportive interventions are likely to be key factors in improving survival from Ebola virus disease."
Dr. Patrick L. Iversen from Sarepta Therapeutics, Inc. in Cambridge, Massachusetts, has studied several compounds for their activity against Ebola virus.
"Both brincidofovir from Chimerix and TKM-Ebola have been used in humans in the current Ebola outbreak but efficacy data are limited or adverse events have been severe so I would not recommend them," Dr. Iversen, also at Oregon State University in Corvallis, told Reuters Health by email.
"The selective estrogen receptor agonists such as toremifene and the antimalarial agent chloroquine have demonstrated efficacy in mouse models of Ebola at more modest doses than favipiravir and both are readily available suggesting equivalent rationale to favipiravir for current human studies," he said.
A compound under development by Sarepta (AVI-7537) and a Biocryst compound (BCX4430) have also shown promise in animal models, and both are in phase 1 trials in humans.
Dr. Iversen concluded, "The most ethical approach to Ebola patients would be to use the most advanced Ebola antiviral drugs, those agents that have demonstrated efficacy in multiple animal models including nonhuman primates and those agents with human safety data. Pharmacokinetic data comparisons between nonhuman primates and humans would also be preferred over comparisons between mouse and human."
OLIGOMER 2015 OXFORDWelcome to OLIGO 2015 Oxford We are delighted to announce our first Oxford Symposium on antisense and therapeutic oligonucleotides.
The symposium is aimed at bringing together chemists and biologists from academia and industry to discuss the latest advances and breakthroughs in the development of synthetic oligonucleotides as therapeutics. We hope this symposium will form the foundations of an annual gathering of oligonucleotide researchers at Oxford.
The symposium agenda is currently in progress. We invite proposal for oral presentations, in particular on THERAPEUTIC APPLICATIONS AND DELIVERY STRATEGIES of synthetic oligonucleotides, including:
Toxicity and pharmacokinetics
Effective therapies for the prevention and treatment of the deadly Ebola virus are urgently needed. A promising approach involves the use of synthetic antisense molecules called phosphorodiamidate morpholino oligomers (PMOs), which are able to target viral mRNA and suppress translation.
US researchers have previously shown that a combination PMO targeting genes that code for two proteins, VP24 and VP35, protected monkeys from lethal Ebola virus infection. Now, the team has found that a PMO targeting VP24 alone conferred protection, whereas a PMO targeting VP35 alone was ineffective.
The finding suggests that VP24 is an important virulence factor encoded by the Ebola virus, the researchers conclude in mBio (online, 10 February 2015). Furthermore, using a single PMO will simplify drug development and regulatory approval.
Use of the compounds PMO and 2OMePS as currently in clinical trials is limited by their low efficiency and high variability in exon skipping and dystrophin induction in all muscles, as revealed from studies in both animal models and the clinical trials. One special concern is the very low efficiency of exon skipping in cardiac muscle, which in boys with DMD is severely affected by the lack of dystrophin expression. Results from animal model studies suggest that a detectable dystrophin induction in cardiac muscle will require biweekly injections of PMO at 60 mg/kg.23 This has led to the use of cationic peptides and other polymers to improve the efficiency of PMO delivery.15,16,24–28 PMOs conjugated with an arginine-rich peptide (PPMO) were able to restore dystrophin expression to near-normal levels in bodywide skeletal muscle and to approximately 50% in cardiac muscle at a dose of 30 mg/kg by single injection. Such high levels of dystrophin expression significantly improved function of both skeletal and cardiac dystrophic muscle.15 However, it is well documented that the use of positively charged peptides and polymers increases toxicity considerably.15,16,26–28 This together with the requirement of lifelong AO drug administration for treating DMD necessitates investigation of these modified PMOs for their long-term applicability and efficacy in relevant animal models in vivo.
In the present study, we investigated the acute toxicity and dose-related 1-year efficacy of PPMO treatment targeting mouse dystrophin exon 23 systemically in dystrophic mdx mice. Our results show that PPMO has a high level of acute toxicity (the LD50 is approximately 85 mg/kg). However, the effective dose for inducing 20% dystrophin in skeletal muscle and 5% dystrophin in cardiac muscle requires only 6 mg/kg biweekly injections with no obvious acute or chronic adverse effects were detected. PPMO could therefore be an effective candidate compound as AO drugs for long-term treatment of DMD.
100.00 a share ,they could make all the monies back in 3-4 years ''or stock swap'' and cost zero.
proven so far for 168 weeks'' Sarepta's ''
confirmation only 22 weeks away ....
IF IT IS DIFFERENT FROM SAREPTA'S THEY WILL SPEND 10 YEARS FROM THE START TO FINISH FOR ANY DRUG.''10 YEARS BEHIND''
I see a 150 percent stock gain from now to approval and much more on approval and more again based on sales
Sarepta is under valued by far right now.
nothing to big .
Let us put it another way buy same thing''dosing closer together could make drug uptake a more constant
I was thinking of doing that..''new small trial ''3 boys being dosed every 3 days . I also think after time say 144 weeks the body starts expelling the pmo-s a little faster and causing the patch process to be less effective..''like patch on,patch off''repeating '' the only way to correct is closer dosing treatments..'' or constant application.