A recent breakthrough in medical research has been made by a team of scientists from the National Centre for Cell Science (NCCS) based in Pune. In their quest to combat drug resistance in Kala-azar (visceral leishmaniasis), they have successfully uncovered new biomolecules. The NCCS is an autonomous body functioning under the Department of Biotechnology, Government of India, primarily established to boost cell biology research in the nation.
Understanding Leishmaniasis
Leishmaniasis, categorised as one of the neglected tropical diseases, affects almost 100 countries, including India. Such diseases are a diverse set of communicable illnesses that prosper in tropical and subtropical conditions, impacting 149 countries. The causative agent of Leishmaniasis is a parasite called Leishmania, which is transported through sand fly bites.
The Varied Manifestations of Leishmaniasis
There are three types of leishmaniasis. Visceral leishmaniasis impacts multiple organs and is the most severe form of the disease. Another variant is cutaneous leishmaniasis, resulting in skin sores and noted as the most prevalent form. Lastly, mucocutaneous leishmaniasis provokes skin and mucosal lesions. Notably, visceral leishmaniasis or Kala-azar, as it is commonly referred to in India, if left untreated, can be fatal in over 95% of the cases.
Challenges in Existing Treatment of Leishmaniasis
The main obstacle in treating leishmaniasis lies in the development of resistance to the only available drug, miltefosine. The effectiveness of miltefosine is declining swiftly due to the decreased accumulation of this drug inside the causative parasite, which has led to the emergence of resistance.
Proteins: Key Role Players in Drug Resistance
Two proteins play a significant role in drug intake within the parasite’s body. The protein ‘P4ATPase-CDC50’, is accountable for the absorption of the drug by the parasite. Simultaneously, another protein, ‘P-glycoprotein’, expels the drug from the parasite’s body. An increase in the latter protein’s activity and a reduction in the former’s lead to less miltefosine accumulation in the parasite’s body, thereby causing drug resistance.
Addressing Miltefosine Resistance: A Strategic Approach
The researchers’ strategic approach to overcome miltefosine resistance involved working with Leishmania major, one of the species causing infection. They made an attempt to influence the transporter proteins in this species to magnify the drug uptake and minimise its expulsion from the parasite’s body.
Novel Use of Peptides to Improve Drug Effectiveness
Scientists employed computational methods to design distinct small molecules, peptides, to interact specifically with Leishmania major’s transporter proteins. These peptides don’t interfere with human proteins, circumventing potential adverse effects. These are short chains of amino acids that are organic compounds combining to form proteins.