Efficacy Of Increasing Doses Of TPI ASM8 On Allergen Inhalation Challenges In Asthmatics

Gauvreau, Gail M.; Séguin, Rosanne; Carballo, D. Calero; Danjou, H.; Campbell, Heather; Watson, Richard M.; Parry-Billings, Mark; Killian, Kieran J.; Renzi, Paolo

doi:10.1164/ajrccm-conference.2010.181.1_meetingabstracts.a5669

Cited by 4 publications

(3 citation statements)

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“…In mild asthmatics, TPI‐ASM8 attenuated allergen‐induced increases in mRNA of the common β chain and CCR3, and also significantly reduced the early asthmatic response and sputum eosinophilia (85). A subsequent study demonstrated dose‐response relationships for these effects, significant attenuation of the late asthmatic response, and tolerability at all tested doses (86). In a rat model of asthma, TPI‐ASM8 added to nebulized budesonide showed a synergistic, dose‐dependent reduction of eosinophil recruitment induced by allergen challenge and decreased bronchoalveolar lavage fluid levels of monocyte chemotactic protein‐1 (MCP‐1) and IL‐13, suggesting that TPI‐ASM8 may be an effective adjunctive treatment in asthma (87).…”

Section: Eosinophilsmentioning

confidence: 93%

Immune modulation for treatment of allergic disease

Nguyen

Casale

2011

Immunological Reviews

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Immune modulation for treatment of allergic diseases aims to decrease the pathologic immune response rather than to cause a return to an immunologically naive or unresponsive state. Our expanding knowledge of innate and adaptive immune responses at the molecular level has led to development of immunomodulators for several allergic diseases, particularly asthma, allergic rhinitis, and eosinophilic esophagitis. Although successful immune modulation in mouse models of allergic disease have often failed to translate into significant results in human clinical trials, much has been learned about the pleotropic nature of cytokines and their effector mechanisms and of the varied phenotypes of allergic disease. We examine strategies of immune modulation in allergic diseases that have undergone human clinical trials, all with the common goal of decreasing the T-helper 2 (Th2) response, but through different mechanisms: blocking critical Th2 cytokines, inhibiting Th2 cytokine synthesis, blocking critical Th2 effector molecules, inhibiting important cells in the Th2 response, and stimulating Th1 responses. Therapies directed against specific effector molecules, such as immunoglobulin E and prostaglandin D2, hold promise in immune modulation of allergic disease, as do targeting the IL-4/IL-13 receptor and augmenting Th1/Th2 balance with Toll-like receptor agonists.

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Section: Eosinophilsmentioning

confidence: 93%

Immune modulation for treatment of allergic disease

Nguyen

Casale

2011

Immunological Reviews

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“…The phase 2a studies that have been performed until now have not shown any of this potential toxicity but longer term studies are needed to confirm these results. Furthermore, to date AON have been delivered via inhalation of a nebulisate to asthma patients (Gauvreau et al 2008;Gauvreau 2010), but not to COPD patients who have severely decreased FEV 1 . How well this patient cohort inhales the nebulisate would need to be determined.…”

Section: Discussionmentioning

confidence: 99%

“…An initial Phase 2 study design does not test in COPD patients but rather in allergic asthmatic patients following inhaled allergen challenge (2009). Another AON drug, ASM8 designed specifically for asthma and as such has targets different from PXS TPI1100, has demonstrated clinical efficacy in this allergen challenge model (Gauvreau et al 2008;Gauvreau 2010) clearly showing the potential for the AON approach. An advantage of this allergen challenge model is that the studies are generally brief in duration and the fall in FEV 1 is a well-recognized response as well as the incorporation of monitoring induced sputum allows for other inflammatory indicators to be measured.…”

Section: Challenges In Copd Clinical Studiesmentioning

confidence: 99%