Effects Of Asthma And Masitinib

The current situation of asthma

There are a large proportion of asthmatic patient in the world. As we known, asthmatic can be satisfactorily treated by combining anti-inflammatory drugs and bronchodilators. Asthma is a chronic inflammatory condition, with bronchial recruitment, activation of inflammatory cells and enhanced release of mediators. Besides, a complete absence of response to corticosteroids in severe asthma is rare while reduced responsiveness, which is often described as corticosteroid-dependent asthma, is more common. Inhaled and oral corticosteroids are required to manage severe cases. These asthmatic patients who remain symptomatic represent a major health and clinical problem and give rise to asthma-associated health care costs.

Factors that influence asthma control such as exposure to environmental hazards, co-morbidities, and medication compliance, as well as inhalation technique should be considered for diagnosis. Patients usually report recurrent symptoms, occurrence of exacerbations and a daily requirement of rescue medications. Although these patients account for only a small part proporation, lack of disease control contributes significantly to their poor quality of life. Finally, patients with severe asthma who require long-term oral steroid therapy usually comply with the treatment but are at higher risk of harmful side-effects.

Agents for treatment of asthma

Therefore, biological agents which are elaboratively designed to interfere with immune targets have been extensively explored, but lots of results were disappointing. To date only omalizumab, which is an anti-immunoglobulin E antibody, has EMEA approval for severe allergic asthma. Nonetheless, a significant proportion of severe asthmatics are not allergic or are not managed by this kind of therapeutic method. And so novel and efficacy drugs are urgently needed to control this type of severe refractory asthma.[1]

Signaling transduction pathway involved in asthma

As previously described, asthma belongs to a chronic inflammation. Dendritic and mast cells are likely to play a key role in severe asthma. These cells can be activated through the engagement of the stem cell factor (SCF) receptor c-kit. Prevention of the SCF/c-kit signaling pathway results to significant decrease of the mast cell population, histamine levels and eosinophile infiltration, interleukin-4 production and airway hyper-responsiveness in vivo, implying that SCF/c-kit may be a potential therapeutic target. Experimental results revealed that dendritic cells expressing nonfunctional c-kit elicited diminished allergic airway inflammation. Also, growth factors such as platelet-derived growth factor (PDGF) contribute to bronchial remodeling, a characteristic of severe asthma, and targeting PDGF receptor tyrosine kinase may be an interesting novel therapeutic option.

Introduction of mastitinib

Masitinib (also called AB1010) and imatinib (also called Glivec or STI571) are protein tyrosine kinase inhibitors, which potently and selectively prevent c-kit and PDGF receptors. Accordingly, masitinib and imatinib are currently developed in various nononcologic chronic diseases characterized by chronic inflammation and remodeling. In this randomized, dose-ranging, placebo-controlled trial, a 16-week treatment with masitinib was a safe and efficient add-on option in corticosteroid-dependent severely asthmatic patients.[2] Conclusively, masitinib may represent an innovative avenue of treatment in corticosteroid-dependent asthma.

References:
[1] Allergy. 2009 Aug;64(8):1194-201.
[2] Asthma. N Engl J Med 2001;344:350362.


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