Future Plan

Future Plan

Following are some diseases that can be potentially treated with our PEPDEX systems. Our focus will be put on the immunological diseases, such as anti-allergy therapies and anti-cancer vacicines.



● Neurological diseases

Alzheimer disease (Perry and Greig 2004; Li, Duffy et al. 2010)

Multiple sclerosis (Bielekova et al. 2000; Holz et al. 2000; Jurynczyk et al. 2010)

Parkinson’s disease (Szeto 2006)

Epilesy (Brothers and Wahlestedt 2010)

● Psychiatric diseases

Anxiety disorder (Holmes et al. 2003; Leonard et al. 2008; Steckler 2008; Madaan and Wilson 2009)

Depression (Holmes et al. 2003; Leonard et al. 2008; Madaan and Wilson 2009)

Eating disorder (Brothers and Wahlestedt 2010)


● Anti-cancer vaccine

Melanoma(Minor 2011; Schwartzentruber, Lawson et al. 2011)

Cervical cancer (Zwaveling, Ferreira Mota et al. 2002)

● Anti-allergy vaccine

Asthma (Campbell, Buckland et al. 2009)

Rheumatoid arthritis (Holgate and Broide 2003)

Allergic rhinitis (Larche and Wraith 2005) (Takagi, Hiroi et al. 2005)

Immunological therapy

Asthma (John D. Campbell, JEM, 2009) (Campbell, Buckland et al. 2009)

There are many mucosal-associated lymphoid systems in the human body, which can react quickly as they usually lie in the host-environmental interfaces. There are many site-specific names for these immune organs; for instance, they are called gut-associated lymphoid tissue system (GALT). In our delivery system, we aim to send and present our peptides through gut-associated lymphoid tissue, since it is one of the biggest and most sophisticated immune systems inside our body, and the system works pretty well in discriminating the pathogens and common normal flora. We try to manipulate this characteristic to design our anti-allergy peptide.

Microfold cells (Wershil and Furuta 2008), abbreviated M cell, are cells found in the follicle-associated epithelium, especially in guts, and deliver foreign antigen to the underlying dendritic cells. The interaction of dendritic cells with the different types of cognate T-cell decides the outcome of immune responses, either adaptive immune responses against certain pathogens or tolerance establishment. The main determinant of the two polarized responses is not yet clear, but the current assumption points to the different types of T-cells activated after antigenic challenges (Iwasaki and Kelsall, 2001). In our project, we planned to deliver anti-allergic peptide by engineered E. coli, which would carries Fel d1, the major cat allergen, as documented(Campbell, Buckland et al. 2009). The anti-allergic peptide requires repetitive challenges, and thus express the Fel d1 through a constitutive, thermal-inducible promoter, Phs (Taylor, Straus et al. 1984). The constitutive presence of the peptide itself would desensitive the reactive immune cells, and establish the local and systemic tolerance, as proved (MacPherson and Liu 1999).


McCoy AT, et al. (2012). Evaluation of metabolically stabilized angiotensin IV analogs as pro-cognitive/anti-dementia agents. JPET #199497.

Benoist CC, et al. (2011). Facilitation of hippocampal synaptogenesis and spatial memory by C-terminal truncated Nle1-angiotensin IV analogues. JPET #182220.

Li Y, et al. (2010) GLP-1 receptor stimulation reduces amyloid-β peptide accumulation and cytotoxicity in cellular and animal models of Alzheimer’s disease. J Alzheimers Dis 19(4): 1205–1219.

Biswas SC, et al. (2008) Glucagon-like Peptide-1 (GLP-1) Diminishes neuronal degeneration and death caused by NGF deprivation by suppressing Bim induction. Neurochem Res 33:1845–1851.

Lin L. (2008) Commonality between diabetes and Alzheimer’s disease and a new strategy for the therapy. Clinical Medicine: Pathology 1: 83–91.

Li Y, et al. (2009) GLP-1 receptor stimulation preserves primary cortical and dopaminergic neurons in cellular and rodent models of stroke and Parkinsonism. Proc Nat Acad Sci 106(4): 1285-1290.

Mossello E, et al. (2011) Glucagon-like peptide-1, diabetes, and cognitive decline: Possible pathophysiological links and therapeutic opportunities. Experimental Diabetes Research 2011:1-6.

Abbas T, et al. (2009) Impairment of synaptic plasticity and memory formation in GLP-1 receptor KO mice: Interaction between type 2 diabetes and Alzheimer’s disease. Behavioural Brain Research 205:265–271.

Holst JJ, et al. (2011) Neuroprotective properties of GLP-1: theoretical and practical applications. Current Medical Research & Opinion 27(3):547–558.

Bak AM, et al. (2011) Targeting amyloid-beta by glucagon-like peptide -1 (GLP-1) in Alzheimer’s disease and diabetes. Expert Opin. Ther. Targets 15(10):1153-1162.

McClean PL, et al. (2011) The diabetes drug Liraglutide prevents degenerative processes in a mouse model of Alzheimer’s disease. The Journal of Neuroscience 31(17):6587–6594.

Pratley RE. (2008) The new science of GLP-1: Effects beyond glucose control. Adv Stud Med. 8(11):393-399.

Leonard SK, et al. (2008). Pharmacology of neuropeptide S in mice: therapeutic relevance to anxiety disorders. Psychopharmacology 197:601–611.

Brothers SP and Wahlestedt C. (2010). Therapeutic potential of neuropeptide Y (NPY) receptor ligands. EMBO Mol Med 2:429–439.

Madaan V and Wilson DR. (2009). Neuropeptides: Relevance in treatment of depression and anxiety disorders. Drug News Perspect 22(6):319-25.

Holmes A. (2003) .Neuropeptide systems as novel therapeutic targets for depression and anxiety disorders. TRENDS in Pharmacological Sciences 2(11):580-9.

Campbell, J. D., K. F. Buckland, et al. (2009). "Peptide immunotherapy in allergic asthma generates IL-10-dependent immunological tolerance associated with linked epitope suppression." J Exp Med 206(7): 1535-1547.

Iwasaki, A. and B. L. Kelsall (2001). "Unique functions of CD11b+, CD8 alpha+, and double-negative Peyer's patch dendritic cells." J Immunol 166(8): 4884-4890.

MacPherson, G. G. and L. M. Liu (1999). "Dendritic cells and Langerhans cells in the uptake of mucosal antigens." Curr Top Microbiol Immunol 236: 33-53.

Taylor, W. E., D. B. Straus, et al. (1984). "Transcription from a heat-inducible promoter causes heat shock regulation of the sigma subunit of E. coli RNA polymerase." Cell 38(2): 371-381.

Wershil, B. K. and G. T. Furuta (2008). "4. Gastrointestinal mucosal immunity." J Allergy Clin Immunol 121(2 Suppl): S380-383; quiz S415.