Leprosy

=__**Disease/Drug of interest** : __=

**Motivation and Background** :
Hansen’s disease, commonly known as leprosy, is an infectious disease caused by Mycrobacterium leprae. Leprosy carries a great stigma due to its biblical references as well as the fear associated with what the disease used to be hundreds of years ago; therefore, the disease is now referred to as Hansen’s disease, named after Doctor Gerhard H. A. Hansen who discovered the bacillus which causes the disease, in 1873. Hansen’s disease is largely misconceived in its frequency, contractibility, and effects.

To address some of these misconceptions, ninety-five percent of people have a strong natural defense against the Mycrobacterium leprae [1]. Of the five percent of the world’s population who have a weak or non-existent natural defense only those exposed to an untreated individual, can contract the disease. Hansen’s disease can also only be contracted through airborne exposure, and is not transmitted through physical contact, exposure to bodily fluids, or from a pregnant mother to her child through child birth. Although Hansen’s disease may often be associated with loss of fingers or toes, this is an indirect effect of the disease. Hansen’s disease can lead to numbness and eventually loss of feeling in extremities if untreated. If this occurs one becomes more vulnerable to reoccurring injuries, these injuries may go unnoticed long enough to cause infections which then may result in loss of fingers, toes or more depending on the severity of the infection. With these clarifications, aside, Hansen’s disease continues as a factor of morbidity in developing countries as the world sees 250,000 new cases of Hansen’s disease each year [2].

Mycrobacterium leprae can incubate in the body for anywhere between three years and a decade; when symptoms begin to surface, rapid response is necessary to prevent permanent nerve damage. Mycrobacterium leprae begins causing nerve injury by attacking Schwann cells. By binding to Schwann cells, Mycrobacterium leprae induces demyelination in peripheral nerves and loss of conductance within the axons of nerve cells [3]. The bacillus invades the Schwann cells through a laminin-binding protein linkage between the cytoskeleton and the extracellular matrix. In the past decades, Hansen’s disease has been treated multidrug therapy, lasting between six months and a year depending on the classification of the bacillus. The classification between multibacillary and paucibacillary is determined by the number of lesions exhibited by the disease; patients exhibiting five or less lesions are classified as paucibacillary, and multibacillary for those with more than five lesions.

=__**Target Information** : __= Dapsone, rifampicin, and clofazimine primarily target the production of folic acid, which is essential to the survival of //Mycobacterium Leprae//. Additionally these drugs inhibit bacterial RNA polymerase.
 * Size: ** 441.3975 g/mol
 * Formula: **C19H19N7O6

** Location ** :

 * Function in a normal cell ** : Folic acid aids in the production and maintainence of new cells. Interestingly folic acid also prevents changes in DNA which may lead to Cancer, so by preventing the production of folic acid, these drugs may eventually result in cancer.

=__**Drug Information**** : **__ There are three drugs currently being used to treat Hansen's Disease in a multi-drug therapy. Dapsone and rifampicin are administered together for pauci-bacillary disease patients, and in cases of multi-bacillary disease, clofazimine is added to the treatment process. =


 * Schematic figure of drug ** : Left to Right: Dapsone, rifampicin, clofazimine



DADPS || Benemycin Rifadin Tubocin || Lamprine B663 ||
 * ||< **Dapsone** || **Rifampicin** || **Clofazimine** ||
 * **Chemical Formula** ||< C 12 H 12 N 2 O 2 S || C 43 H 58 N 4 O 12 || C 27 H 22 Cl 2 N 4 ||
 * **Molecular weight** ||< 248.3 g/mol || 822.953 g/mol || 473.401 g/mol ||
 * **CAS Number** ||< 80-08-0 || 13292-46-1 || 2030-63-9 ||
 * **Alternative Names** ||< Avlosulfone


 * Delivery method ** : All three drugs, Dapson, rifampicin, and clofazimine, can be administered either intravenously or orally.
 * Side effects ** : Treatment of Hansen's Disease with these three drugs may often result in discoloration of the recipient's skin, sweat, urination, tears and other bodily fluids. It is also highly advised that patients with liver disease do not take any of the drugs as it may result in death.
 * Patents and Production: ** All three of the drugs have multiple patents, for multiple forms of the drug.
 * Clinical Trials Info ** : Clofazimine is still under extensive trials and is only used in extreme cases of Hansen's disease because although it is very effective, there is much about the drug and its effects that are still not completely known.

__** Origin ** : __


 * Alternatives to this drug ** : Currently these drugs are the only drugs being used to treat Hansen's Disease in this way.
 * Miscellaneous ** :
 * Other uses ** : Cumulatively these drugs can treat dermatitis, tuberculosis, neisseria meningitis, and hemophilus influenza.


 * References: **

1. Texas Department of Safe Health Services (Accessed through http://www.dshs.texas.gov/idcu/disease/hansens/) 2. Mattos, K; Oliveira, V; Mycobacterium leprae intracellular survival relies on cholesterol accumulation in infected macrophages: a potential target for new drugs for leprosy treatment. Cellular microbiology 2014, 16, (6), 797-815. (Accessed through http://onlinelibrary.wiley.com/doi/10.1111/cmi.12279/full)  3. Pinheiro, R.; Salles, J; Mycobacterium leprae-host cell interactions and genetic determinants in leprosy; an overview. Future microbial 2011, 6, (2), 217-230. (Accessed through https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3123826/)  4. World Health Organization (Many different studies and reports provided by World Health Organization which have been vital to the treatment of Hansen’s Disease) 5. National Center for Biotechnology Information. PubChem Compound Database; CID=2955, https://pubchem.ncbi.nlm.nih.gov/compound/2955 (accessed Feb. 5, 2017). 6. Stanford.edu (authorship and publication not provided) https://web.stanford.edu/class/humbio103/ParaSites2005/Leprosy/treatment.htm 7. National Center for Biotechnology Information. PubChem Compound Database; CID=5381226, https://pubchem.ncbi.nlm.nih.gov/compound/5381226 (accessed Feb. 5, 2017). 8. National Center for Biotechnology Information. PubChem Compound Database; CID=2794, https://pubchem.ncbi.nlm.nih.gov/compound/2794 (accessed Feb. 5, 2017).