Repurposing of Sodium Thi0sulfate for the Managemnt of Tumoral Calcinosis & “Determination of Stress Levels in University Faculty

Abstract

Orphan diseases means diseases which are less prevalent compared to other commonly occurring diseases and affect limited number of patients. There are over 7000 known rare diseases in this world out of which only 300-400 have established treatment options. These rare diseases and clinical development process for finding treatment for them are far different compared to traditional diseases and their medicines. Hence, in order to find suitable treatment for these diseases in shorter period of time, alternative approaches need to examine. Repurposing generally refers to studying a compound or biologic to treat one disease or condition to see if it is safe and effective for treating other diseases. As per the available data, around 72, 611, 605 patients (which is more than US and EU orphan disease population combined) were having orphan diseases in India up to 2012. Sodium thiosulfate (Na2S2O3• 5H2O) is a colourless crystals or coarse crystalline powder, very soluble in water. Sodium thiosulfate used as chelating agent, anti- browning agent (Brown pigmentation and in food industry as a chemical additive in food processing like prevention of browning of cut fruits, peeled potatoes), anti-oxidant, anti- inflammatory agent and as a preservative. Actively used in the treatment of Cyanide poisoning. The first time potential of sodium thiosulfate unlocked for management of cyanide poisoning and used from 1885 to till date for management of acute cyanide poisoning and for which it holds lots of orphan drug designation. Even before 1925 sodium thiosulfate was specifically known for cyanide antidote only.Aim and Objectives:  To review already existing drugs for their suitability for the treatment of orphan diseases.  To identify at least one drug-disease combination in orphan area.  To develop and get orphan drug designation for the identified drug for management of identified orphan disease in US/EU market. Search Strategy Because of several mechanism and use of sodium thiosulfate we tried to focus use of sodium thiosulfate in calcification disorders. For that we identified total seven orphan disease, Arterialcalcification (Idiopathic Infantile Arterial Calcification), Juvenile Dermatomyositis and Calcinosis Cutis, Nephrogenic Systemic Fibrosis, Tumoral Calcinosis, Nephrocalcinosis, Systemic Lupus Erythematosus, Oxalate nephropathy And Acute Pancreatitis. We tried to repurpose sodium thiosulfate for management of several orphan diseases. Our analysis of several reports suggested the promising effects of Sodium thiosulfate in seven orphan diseases. Sodium thiosulfate has been prescribed as off label for the treatment of tumoral calcinosis. Based on the literature survey, we narrowed down our efforts to identify Sodium thiosulfate as a target for tumoral calcinosis. Tumoral calcinosis is a rare familial condition which is characterized by painless, peri-articular masses. The term is used for a disease caused by a hereditary metabolic dysfunction of phosphate regulation associated with massive peri-articular Calcinosis. We identified 1172 cases of tumoral calcinosis from all over the world. Out of which 129 cases were present in India. Till now there is no specific treatment available for the management of tumoral calcinosis. Results, Discussion and Clinical Trial outlook Sodium thiosulfate has been used as an off label treatment for management tumoral calcinosis in several countries. We approached off-target mechanism for repurposing of sodium thiosulfate in calcification disorders where mechanism of sodium thiosulfate as a chelating agent is taken into the consideration for treatment of several diseases. We also found several other disease in which sodium thiosulfate can be used but because of lack of evidence we couldn’t proceed further. We also propose a clinical trial outlook of sodium thiosulfate treatment for tumoral calcinosis. We hope to get orphan drug designation for sodium thiosulfate for management of tumoral calcinosis in future. Conclusion There are total 15 orphan drug designations filed for sodium thiosulfate in United States and Europe. Sodium thiosulfate is used as off-label for the treatment of seven orphan diseases. But no orphan drug designation of Sodium thiosulfate was filed for any of the above mentioned diseases. 16 evidences were found where in sodium thiosulfate was used for the treatment of tumoral calcinosis establishing its chelating mechanism. Based on the evidences Sodium thiosulfate can be repurposed and designated for tumoral calcinosis. We are hopeful that ourclinical trial outlook will be taken up by some industry and Sodium thiosulfate will get an orphan designation for tumoral calcinosis in future.