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Efficacy of CMX001 as a prophylactic and presymptomatic antiviral agent in New Zealand white rabbits infected with rabbitpox virus, a model for orthopoxvirus infections of humans.

Rice AD, Adams MM, Lampert B, Foster S, Robertson A, Painter G, Moyer RW - Viruses (2011)

Bottom Line: CMX001 has dramatically increased potency versus CDV against all dsDNA viruses and, in contrast to CDV, is orally available and has shown no evidence of nephrotoxicity in healthy volunteers or severely ill transplant patients to date.In the absence of human cases of smallpox, new treatments must be tested for efficacy in animal models.Our results should also be applicable to monkeypox virus infections and for treatment of adverse reactions to smallpox vaccination.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610, USA. amandar@ufl.edu

ABSTRACT
CMX001, a lipophilic nucleotide analog formed by covalently linking 3-(hexdecyloxy)propan-1-ol to cidofovir (CDV), is being developed as a treatment for smallpox. CMX001 has dramatically increased potency versus CDV against all dsDNA viruses and, in contrast to CDV, is orally available and has shown no evidence of nephrotoxicity in healthy volunteers or severely ill transplant patients to date. Although smallpox has been eliminated from the environment, treatments are urgently being sought due to the risk of smallpox being used as a bioterrorism agent and for monkeypox virus, a zoonotic disease of Africa, and adverse reactions to smallpox virus vaccinations. In the absence of human cases of smallpox, new treatments must be tested for efficacy in animal models. Here we first review and discuss the rabbitpox virus (RPV) infection of New Zealand White rabbits as a model for smallpox to test the efficacy of CMX001 as a prophylactic and early disease antiviral. Our results should also be applicable to monkeypox virus infections and for treatment of adverse reactions to smallpox vaccination.

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Clinical observations for evaluation of minimum dosage of CMX001 to provide protection from RPV disease. Animals were dosed at concentrations and schedules as outlined in Table 1. (A) Average weight change from weight at day of infection. Negative values indicated weight loss. (B) Average body temperatures. (C) Average clinical scores. (D) Pictures of primary lesions from representative animals at 7 dpi. Bars represent 1 cm. Black circles denote site of intradermal inoculation.
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f4-viruses-03-00063: Clinical observations for evaluation of minimum dosage of CMX001 to provide protection from RPV disease. Animals were dosed at concentrations and schedules as outlined in Table 1. (A) Average weight change from weight at day of infection. Negative values indicated weight loss. (B) Average body temperatures. (C) Average clinical scores. (D) Pictures of primary lesions from representative animals at 7 dpi. Bars represent 1 cm. Black circles denote site of intradermal inoculation.

Mentions: Although all the animals that received CMX001 were protected from lethal RPV disease there was a difference in clinical symptoms that was dependent on the dose of CMX001 received. Animals treated with 5 or 10 mg/kg BID or 20 mg/kg QD exhibited few clinical symptoms over the course of the experiment. All three treatment groups exhibited a positive weight change, indicating a nearly constant weight gain, with no significant differences between groups (Figure 4A). Animals that received 1 mg/kg of CMX001 exhibited a weight loss profile similar to that of the vehicle treated animals (Figure 4A).


Efficacy of CMX001 as a prophylactic and presymptomatic antiviral agent in New Zealand white rabbits infected with rabbitpox virus, a model for orthopoxvirus infections of humans.

Rice AD, Adams MM, Lampert B, Foster S, Robertson A, Painter G, Moyer RW - Viruses (2011)

Clinical observations for evaluation of minimum dosage of CMX001 to provide protection from RPV disease. Animals were dosed at concentrations and schedules as outlined in Table 1. (A) Average weight change from weight at day of infection. Negative values indicated weight loss. (B) Average body temperatures. (C) Average clinical scores. (D) Pictures of primary lesions from representative animals at 7 dpi. Bars represent 1 cm. Black circles denote site of intradermal inoculation.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3045966&req=5

f4-viruses-03-00063: Clinical observations for evaluation of minimum dosage of CMX001 to provide protection from RPV disease. Animals were dosed at concentrations and schedules as outlined in Table 1. (A) Average weight change from weight at day of infection. Negative values indicated weight loss. (B) Average body temperatures. (C) Average clinical scores. (D) Pictures of primary lesions from representative animals at 7 dpi. Bars represent 1 cm. Black circles denote site of intradermal inoculation.
Mentions: Although all the animals that received CMX001 were protected from lethal RPV disease there was a difference in clinical symptoms that was dependent on the dose of CMX001 received. Animals treated with 5 or 10 mg/kg BID or 20 mg/kg QD exhibited few clinical symptoms over the course of the experiment. All three treatment groups exhibited a positive weight change, indicating a nearly constant weight gain, with no significant differences between groups (Figure 4A). Animals that received 1 mg/kg of CMX001 exhibited a weight loss profile similar to that of the vehicle treated animals (Figure 4A).

Bottom Line: CMX001 has dramatically increased potency versus CDV against all dsDNA viruses and, in contrast to CDV, is orally available and has shown no evidence of nephrotoxicity in healthy volunteers or severely ill transplant patients to date.In the absence of human cases of smallpox, new treatments must be tested for efficacy in animal models.Our results should also be applicable to monkeypox virus infections and for treatment of adverse reactions to smallpox vaccination.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610, USA. amandar@ufl.edu

ABSTRACT
CMX001, a lipophilic nucleotide analog formed by covalently linking 3-(hexdecyloxy)propan-1-ol to cidofovir (CDV), is being developed as a treatment for smallpox. CMX001 has dramatically increased potency versus CDV against all dsDNA viruses and, in contrast to CDV, is orally available and has shown no evidence of nephrotoxicity in healthy volunteers or severely ill transplant patients to date. Although smallpox has been eliminated from the environment, treatments are urgently being sought due to the risk of smallpox being used as a bioterrorism agent and for monkeypox virus, a zoonotic disease of Africa, and adverse reactions to smallpox virus vaccinations. In the absence of human cases of smallpox, new treatments must be tested for efficacy in animal models. Here we first review and discuss the rabbitpox virus (RPV) infection of New Zealand White rabbits as a model for smallpox to test the efficacy of CMX001 as a prophylactic and early disease antiviral. Our results should also be applicable to monkeypox virus infections and for treatment of adverse reactions to smallpox vaccination.

Show MeSH
Related in: MedlinePlus