Mesenchymal Trophic Factor
Safety and Feasibility Study of Intranasal Mesenchymal Trophic Factor (MTF) for Treatment of Asthma
Asthma is a chronic illness affecting some 235 million people worldwide. Asthma can be triggered by immunologic stimuli and is characterized by chronic inflammation of the airways. Mesenchymal stem cells (MSC) are effective at treating allergic airway inflammation in a mouse model of asthma [1-3]. Mechanisms of therapeutic activity appear to be associated with regenerative and anti-inflammatory factors produced by MSC [4,5]. Mesenchymal trophic factor (MTF) is a preparation of cytokines and growth factors that are collected from the conditioned media of MSC grown in animal-free media. MTF allows for subjects to be provided various benefits of MSC therapy without the need to administer cells. This allows for larger accessibility of treatment, as well as potential economic benefit. MTF has been demonstrated to possess anti-inflammatory [6,7], antioxidant , antifibrotic , and regenerative properties  in vitro and in vivo.
The proposed study will involve twenty subjects suffering from asthma. The subjects will be treated a total of 4 times with 2 ml of intranasal MTF, one time per week for 4 weeks. The primary endpoint will be safety and feasibility as assessed by lack of adverse events related to the MTF. The secondary endpoint will be improvements in pulmonary function and quality of life as measured by FEV1 and FVC following ATS guidelines and the University of Pittsburgh Medical Center (UPMC) Asthma Questionnaire (http://www.asthmainstitute.pitt.edu/asthma control.html). Patients will be examined at baseline and weekly during treatment, as well as at one week and at one month following the final dose of MTF.
This study is intended to provide support for subsequent larger, controlled investigations. The potential of using MTF for this debilitating condition will open the door for future investigations in other inflammatory conditions if results demonstrate safety and feasibility of this approach.
- Signed consent form by the subject
- Male or female
- Between 21 and 60 years old and capability to comprehend this trial.
- Asthma diagnosed by a physician at least 1 year prior to study enrollment
- Poorly-controlled asthma at study enrollment. Poorly controlled asthma is defined as: chronic symptoms, episodic exacerbations, persistent and variable airways obstruction despite a continued requirement for short-acting beta 2-agonists despite the use of high doses of inhaled steroids.
- Nonsmokers (stopped smoking at least 1 year ago) and limited life-time history of smoking (less than a 3 pack year history).
- Body mass index 19-31
- On a stable dose of inhaled corticosteroid for at least 4 weeks prior to study entry
- FEV1 >50% predicted
- Pregnant or lactating women
- Cognitively impaired adults
- Systemic steroids within the 4 weeks prior to enrollment
- Non-steroidal anti-inflammatory drugs (NSAIDs) for arthritis
- Current diagnosis of polyposis or sinusitis.
- Infection treated by antibiotics within the 4 weeks prior to enrollment
- Immunization within the 4 weeks prior to enrollment
- Lung pathology other than asthma
- Other significant non-pulmonary co-morbidities such as: coronary artery disease, peripheral vascular disease, cerebrovascular disease, congestive heart failure with an ejection fraction <50%, liver disease or elevated liver enzymes at baseline, malignancy (excluding non-melanoma skin cancers), AIDS, renal failure with serum creatinine >3.0, or disorders requiring steroid treatment such as vasculitis, lupus, rheumatoid arthritis
- Illicit drug use within the past year
- Current/active upper respiratory infection (URI) (if active URI, wait until asymptomatic for 1 week to enroll)
- Asthma exacerbation within the 4 weeks prior to enrollment (includes ER, urgent care, or hospital visits due to asthma resulting in an increase in asthma-related medications)
- Undergoing evaluation for sleep apnea, or plans to institute treatment for sleep apnea (patients on a stable treatment regimen for sleep apnea for the last 3 months prior to enrollment will be allowed to participate)
- Clinically significant abnormalities present on screening 12-lead electrocardiogram
- Women of childbearing potential using oral contraceptives who are not willing to use a second method of contraception during the study
- Participation in another clinical study within 4 weeks prior to enrollment
- Subject does not sign informed consent
- Bonfield, T.L., et al., Human mesenchymal stem cells suppress chronic airway inflammation in the murine ovalbumin asthma model. Am J Physiol Lung Cell Mol Physiol, 2010. 299(6): p. L760-70.
- Ge, X., et al., Intratracheal transplantation of bone marrow-derived mesenchymal stem cells reduced airway inflammation and up-regulated CD4(+)CD25(+) regulatory T cells in asthmatic mouse. Cell Biollnt, 2013. 37(7): p. 675-86.
- Ou-Yang, H.F., et al., Suppression of allergic airway inflammation in a mouse model of asthma by exogenous mesenchymal stem cells. Exp Bioi Med (Maywood}, 2011. 236(12): p. 1461-7.
- van Buul, G.M., et al., Mesenchymal stem cells secrete factors that inhibit inflammatory processes in short-term osteoarthritic synovium and cartilage explant culture. Osteoarthritis Cartilage, 2012. 20(10): p. 1186 96.
- Lo, W.C., et al., Preferential therapy for osteoarthritis by cord blood MSCs through regulation of chondrogenic cytokines. Biomaterials, 2013. 34(20): p. 4 739-48.
- Tsyb, A.F., et al., In vitro inhibitory effect of mesenchymal stem cells on zymosaninduced production of reactive oxygen species. Bull Exp Bioi Med, 2008. 146(1 ): p. 158-64.
- Tu, Z., et al., Mesenchymal stem cells inhibit complement activation by secreting factor H. Stem Cells Dev, 2010. 19(11}: p. 1803-9.
- Kemp, K., et al., Mesenchymal stem cell-secreted superoxide dismutase promotes cerebellar neuronal survival. J Neurochem, 2010. 114(6): p. 1569-80.
- Ortiz, L.A., et al., lnterleukin 1 receptor antagonist mediates the anti-inflammatory and antifibrotic effect of mesenchymal stem cells during lung injury. Proc Natl Acad Sci U S A, 2007. 104(26): p. 11002-7.
- Osugi, M., et al., Conditioned media from mesenchymal stem cells enhanced bone regeneration in rat calvarial bone defects. Tissue Eng Part A, 2012. 18(13-14): p. 1479- 89.