Cystic fibrosis pharmacology

A number of different low molecular weight compounds are known to stablize proteins in their native conformation and, therefore, may be effective in correcting of protein folding abnormalities in vivo. Relevant compounds are iV-acetyl-L-lysine, L-camitine, taurine, betaine, ectoine, and hydroxy-ectoine [4]. Some of these chemical chaperones and pharmacological chaperones are already used in clinical trials to combat protein folding diseases, such as cystic fibrosis. 

Ronghe, M. et al. (2001). Remission induction therapy for childhood acute lymphoblastic leukaemia clinical and cellular pharmacology of vincristine, corticosteroids, L-asparaginase and anthracyclines. Cancer Treat. Rev. 27(6), 327-337. Welsh, M. Smith, A. (1995). Cystic fibrosis. Sci. Am. (December), 36-43. 

Although there is still no cure for cystic fibrosis, several pharmacologic techniques have been recently developed that may help decrease the viscosity of respiratory secretions in patients with this disease. One technique uses aerosol preparations that contain enzymes known as deoxyribonucleases. These enzymes can be inhaled to break down the large quantities of DNA that are present in respiratory secretions of patients with cystic fibrosis.48,104 Respiratory secretions in these patients often contain large amounts of DNA because the genetic material contained in airway in-... 

H. M. Bryson and E, M, Soritin. Dornaac alfa a review of its pharmacological properties and therapeutic potential in cystic fibrosis. Drugs 4ft894-906 (1994). 

Pharmacological Rescue of Mutant CFTR Function for the Treatment of Cystic Fibrosis... 

Gelman, M.S., Kopito, R.R. Rescuing protein conformation prospects for pharmacological therapy in cystic fibrosis (review). J. Clin. Invest. 2002 110 1591-1597... 

A pharmacological role for vitamin E may exist in claudication arising from peripheral vascular disease. Studies with small numbers of patients having cystic fibrosis, glucose-6-phosphate dehydrogenase deficiency, and sickle cell anemia conditions associated with decreased erythrocyte half-lives showed that many had chemical evidence of vitamin E deficiency. Administration of vitamin E supplements (400-800 lU/d) significantly increased red cell survival time. Claims that doses of vitamin E 10-20 times the RDA are beneficial for treatment of skin disorders, fibrocystic breast disease, sexual dysfunction, cancer, baldness, and other disorders have not been substantiated. 

Wallace CS, Hall M, Kuhn RJ. Pharmacologic management of cystic fibrosis. Clin Pharm 1993 12 657-674. 

Yerxa BR, Sabater JR, Davis CW, et al. Pharmacology of INS37217 [P(l)-(uridine 5 )-P(4)-(2 -deoxycytidine 5 )tetraphosphate, tetrasodium salt], a next-generation P2Y2 receptor agonist for the treatment of cystic fibrosis. J Pharmacol Exp Ther 2002 ... 

Pancrelipase, Accelerase Cotazym Ilozyme Ku-Zyme HP Pancrease Viokase. Porcine pancreatic enzyme concentrate containing principally lipase, with amylase and protease. Clinical pharmacology and comparison with pancreatin, q. v. Y. W. Cho, D. M, Aviado, J. Clin. Pharmacol 21, 224 (1981), Clinical trial in cystic fibrosis E. H. Mischler ei al, Am. J. Dis. Child. 136, 1060 (1982) in adult pancreatic insufficiency S. K, Dutta, D. K, Tilley, J. Clin, Gastroenterol 5, 51 (1983). 

Membrane transporters constitute a rather small family of drug targets. Some of them have yet to reveal their relevant therapeutic interest, that is, as targets of diuretics or antide-pressive drugs, but some others stiU resist to pharmacological control, that is, CFTR (Cystic Fibrosis Transmembrane conductance Regulator) for cystic fibrosis therapy and multidmg resistance transporter to improve cancer therapy. 

Describe a process to deliver pharmacological chaperone proteins to treat cystic fibrosis. 

Larry G. Johnson, M.D. Associate Professor, Departments of Medicine and Pharmacology, and Cystic Fibrosis Pulmonary Research and Treatment Center, University of North Carolirra at Chapel Hill, Chapel Hill, North Carolirra, U.S. A. 

Knowles MR, Olivier KN, Hohneker KW, Robinson J, Bennet WD, Boucher RD. Pharmacological treatment of abnormal ion transport in the airway epithelium in cystic fibrosis. Chest 1995 107(suppl) 71S-76S. 

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