Treatment of Leprosy with Clofazimine, Rifampicin and Bayrena

Since 1970, when the lifelong monotherapy with dapsone (DDS) in leprosy could be replaced by short-term combination therapy with rifampicin + isoniazid + protionamide-!-DDS (Isoprodian-RMP), chemotherapeutic research was faced with two problems: (1) to find alternative treatment regimens for cases of intolerance, and (2) to work out forms of therapy allowing a further reduction of the average treatment time of 2 years. The present paper describes the attempts made to find solutions to these problems. With two new combinations, alternatives have become available, and the average treatment time is shortened to 6 months. Both combinations are also effective in tuberculosis.

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“…We agree with Languillon [30], Basset and Samsoen [7] and Coudert et at. [10], that certain sulfonamides are good antileprotic drugs.…”

Section: New Combinations Including Sulfonamidessupporting

confidence: 82%

New Forms of Multidrug Therapy for the Treatment of Leprosy

Freerksen¹,

Rosenfeld²,

Spannuth³

1989

Chemotherapy

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“…In the course of this study, we identified two compounds, including sulfameter and mexenone, that bind to sialidase-1. Sulfameter is an old antibacterial drug that has been used in the treatment of leprosy 26 and urinary tract infections, 27 while mexenone is an active sun screen agent. 28 These compounds have not been previously reported in the literature to bind to sialidase-1, nor are they represented in the machine learning model training set.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Using Bibliometric Analysis and Machine Learning to Identify Compounds Binding to Sialidase-1

Klein

Baker²,

Foil

et al. 2021

ACS Omega

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Rare diseases impact hundreds of millions of individuals worldwide. However, few therapies exist to treat the rare disease population because financial resources are limited, the number of patients affected is low, bioactivity data is often nonexistent, and very few animal models exist to support preclinical development efforts. Sialidosis is an ultrarare lysosomal storage disorder in which mutations in the NEU1 gene result in the deficiency of the lysosomal enzyme sialidase-1. This enzyme catalyzes the removal of sialic acid moieties from glycoproteins and glycolipids. Therefore, the defective or deficient protein leads to the buildup of sialylated glycoproteins as well as several characteristic symptoms of sialidosis including visual impairment, ataxia, hepatomegaly, dysostosis multiplex, and developmental delay. In this study, we used a bibliometric tool to generate links between lysosomal storage disease (LSD) targets and existing bioactivity data that could be curated in order to build machine learning models and screen compounds in silico. We focused on sialidase as an example, and we used the data curated from the literature to build a Bayesian model which was then used to score compound libraries and rank these molecules for in vitro testing. Two compounds were identified from in vitro testing using microscale thermophoresis, namely sulfameter (K d 2.15 ± 1.02 μM) and mexenone (K d 8.88 ± 4.02 μM), which validated our approach to identifying new molecules binding to this protein, which could represent possible drug candidates that can be evaluated further as potential chaperones for this ultrarare lysosomal disease for which there is currently no treatment. Combining bibliometric and machine learning approaches has the ability to assist in curating small molecule data and model building, respectively, for rare disease drug discovery. This approach also has the capability to identify new compounds that are potential drug candidates.

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“…■ Very good results were observed with the combination of dapsone and rifampicin, and there were some evidence of the equivalence of once a month rifampicin with everyday regimen [30][31][32];…”

Section: Who Multidrug Therapy: Rationale Evidence and Criticismsmentioning

confidence: 92%

Considerations in the design of clinical trials for multibacillary leprosy treatment

Penna¹

2014

Clinical Investigation

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In 1991, the World Health Assembly adopted a resolution to attain the goal of global elimination of leprosy as a public health problem by the year 2000, based on universal access to multidrug therapy established by the WHO. The WHO multidrug therapy recommendation was not based on clinical trial results, but was based on all scientific knowledge available at the time and incorporated some financial constraints, such as the impossibility of daily rifampin use. Further decisions regarding treatment duration were needed to allow the World Health Assembly resolution target to be reached, which was set without a deep epidemiological evaluation. At present there are many uncertainties about leprosy treatment, including for instance, its ideal duration including decisions concerning daily or intermittent use of drugs, the use of immune modulators with antibacterial drugs as prophylaxis, and treatment of reactions during and after chemotherapy. To advance our knowledge of leprosy treatment, knowledge revision of the available research would be the first step to develop comprehensive Bayesian clinical trials designed to shed light on these uncertainties.

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Treatment of Leprosy with Clofazimine, Rifampicin and Bayrena

Cited by 5 publications

References 0 publications

New Forms of Multidrug Therapy for the Treatment of Leprosy

New Forms of Multidrug Therapy for the Treatment of Leprosy

Using Bibliometric Analysis and Machine Learning to Identify Compounds Binding to Sialidase-1

Considerations in the design of clinical trials for multibacillary leprosy treatment

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