Protein therapeutic agents

TABLE 12.2 Comparison of Protein Therapeutic Agents with Small Molecule Drugs... 

Galluppi, G.R., M.C. Rogge, L.K. Roskos, L.J. Lesko, M.D. Green, D.W. Feigal, Jr., and C.C. Peck, Integration of pharmacokinetic and pharmacodynamic studies in the discovery, development, and review of protein therapeutic agents a conference report. Clin Pharmacol Ther, 2001. 69(6) 387-99. 

Immunogenicity assays for investigating the frequency and consequences of antibody development against a protein therapeutic agent are typically based on an immunoassay technique (mostly ELIS As of various types). However, other assay formats are available such as radioimmunoprecipitation assay, surface plasmon resonance, and electrochemiluminescence [3]. Assays for measuring antibody response should be established in the early preclinical stage of development to estimate the value of the applied animal models (see Chapters 16 and 20). 

In addition to small molecules, a number of protein therapeutic agents, such as neurotrophic factors27 and insulin,28 have been successfully delivered to the CNS using IN delivery in a variety of species. The therapeutic benefit of IN delivery of proteins has been demonstrated by Liu et al. in rat stroke models.29 Their studies demonstrated that insulin-like growth factor I (IGF-I) could be delivered to the brain directly from the nasal cavity, even though IGF-I did not cross the BBB efficiently by itself. As a consequence, IN IGF-I markedly reduced infarct volume and improved neurological function following focal cerebral ischemia. Research in... 

As mentioned previously in Section 41.2.2.5, age can be a covariate for biologies. The effects of age on the PK properties of a protein appear to be due to changes in endothelial and macrophage function and to a lesser extent to changes in organ blood flow. Alterations of the immune response in elderly patients have been associated with increased amounts of memory and alloreactive T-cells, as well as altered cytokine responses (69), which can impact both on the pharmacokinetics and pharmacodynamics of a protein therapeutic agent. 

Gelatin can be a source of essential amino acids when used as a diet supplement and therapeutic agent. As such, it has been widely used in muscular disorders, peptic ulcers, and infant feeding, and to spur nail growth. Gelatin is not a complete protein for mammalian nutrition, however, since it is lacking in the essential amino acid tryptophan [73-22-3] and is deficient in sulfur-containing amino acids. 

Electrotransport technology offers a number of benefits for therapeutic appHcations, including systemic or local adininistration of a wide variety of therapeutic agents with the potential adininistration of peptides and proteins long-term noninvasive administration, improving convenience and compliance controlled release, providing a desired deflvery profile over an extended period with rapid onset of efficacious plasma dmg levels and in some cases reduced side effects and a transport rate relatively independent of skin type or site. Additional benefits include easy inception and discontinuation of treatment, patterned and feedback-controlled deflvery, and avoidance of first-pass hepatic metaboHsm. 

Alterations to the P53 gene are the most common genetic defects known in cancer [5]. The protein product of P53 is involved in a number of pathways that directly and indirectly lead to apoptosis. Many genes that are involved in apoptosis can be induced by this protein, which is a transcriptional transactivator. The emerging hypothesis is that p53 is a central node of a complex apoptotic network that may function differ ently in diver se cell types and tissues. For example, Bax, the prototype proapoptotic member of the Bcl2 family, can be transcriptionally induced by p53 in certain, but not all, cell types. Like p53, Bax can modulate the extent to which cells are sensitive to apoptosis caused by therapeutic agents. 

Levitzki A (2000) Protein Tyrosine Kinase Inhibitors as Therapeutic Agents. 211 1-15 Li G, Gouzy M-F, Fuhrhop J-H (2002) Recognition Processes with Amphiphilic Carbohydrates in Water. 218 133-158 Li X, see Paldus J (1999) 203 1-20... 

The development of peptides and proteins as therapeutic agents has been greatly accelerated by advances in the fields of biotechnology. 

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