Medicinal Chemistry of Multiple Sclerosis: Focus on Cladribine

Abstract

Background: In the recent years, many novel Disease-Modifying Drugs (DMD) have been introduced to the market in the treatment of multiple sclerosis. Objectives: To provide the reader with an up to date, compact review on the pharmacokinetic properties, mechanism of action, and clinical attributes of one of the most recently approved drugs in the therapy of multiple sclerosis, cladribine. Conclusion: Cladribine tablets proved to be a highly efficient treatment choice for Relapsing- Remitting Multiple Sclerosis (RRMS), especially for patients with high disease activity. It is the first DMD for MS with a complex mechanism of action, by inhibiting the adenosine-deaminase enzyme it increases the intracellular levels of deoxyadenosine triphosphate, which with relative selectivity depletes both T- and B-cells lines simultaneously. However long term follow-up safety and effectiveness data are still missing, and clear treatment protocols are lacking beyond the first two treatment years cladribine should prove to be a valuable addition to the therapeutic palette of RRMS, and potentially for Clinically Isolated Syndrome (CIS) as well.

Mapping the Therapeutic Options for Multiple Sclerosis in Brazil: A Comprehensive Analysis

“…Due to this enzymatic deficiency, levels of deoxyadenosine triphosphate increase within the cells, leading to the destruction of T and B lymphocytes and, consequently, resulting in immunodeficiency. These cells play a crucial role in autoimmune responses, including those related to MS [95].…”

Cladribine Tablets for Relapsing–Remitting Multiple Sclerosis: A Clinician’s Review

“…This activity is counterbalanced by 5-nucleotidase (5′NTase). Cladribine has well-defined and specifically designed activity against lymphocytes that leads to selective depletion and most importantly, cladribine only affects the adaptive immune system whilst sparing innate immune cells, thus reducing the risk of infections [ 4 , 13 , 21 , 22 ]. The high selectivity of cladribine for lymphocytes is due to the high ratio of DCK to 5′NTase and the high ratio of DCK to adenosine deaminase that leads to preferential accumulation in these cells.…”

Magnetic Multi-Enzymatic System for Cladribine Manufacturing

“…Cladribine (Mavenclad, 2-chloro-2′-deoxyadenosine) is a clinical drug for the treatment of hairy cell lymphoid and myeloid leukemia [ 17 ] which has also received EMA and FDA approval for the treatment of relapsing–remitting multiple sclerosis (RRMS) [ 18 ]. Due to its broad clinical applicability, the development of novel, efficient and eco-friendly alternatives to classical chemical methods are gaining ground.…”