Analysis of the clinical efficacy of bosutinib/bosutinib in the treatment of ALS

Bosutinib/Bosutinib (Bosutinib) is a second-generation tyrosine kinase inhibitor (TKI) that is widely used in the treatment of chronic myelogenous leukemia (CML). Its research focus is mainly on the field of hematological tumors. However, in recent years, with the in-depth research on the pathogenesis of neurodegenerative diseases, bosutinib has been gradually introduced into the exploratory treatment of amyotrophic lateral sclerosis (ALS, commonly known as amyotrophic lateral sclerosis) and other diseases. ALS is a progressive neurological disease that primarily affects upper and lower motor neurons, eventually leading to muscle atrophy, weakness and even death. Since there is currently no cure for ALS, the exploration of new mechanisms and new drugs is crucial to improving patients' quality of life and delaying disease progression.

The reason why bosutinib is considered to have the potential to treat ALSis mainly due to its inhibitory activity on Src family kinases. This type of kinase is not only related to the proliferation of tumor cells, but also participates in a variety of signal transduction pathways in nerve cells, especially playing an important role in processes such as neuroinflammation, axonal degeneration, and synaptic transmission. Some cutting-edge basic research and animal model studies have shown that Src inhibitors can slow down the degenerative changes of motor neurons in ALS models, suggesting that such drugs may have neuroprotective effects.

In addition, bosutinib has also been found to have the potential to intervene in the pathological changes ofTDP-43 protein. TDP-43 is one of the core pathological hallmarks of ALS, and its abnormal aggregation is considered to be an important cause of neuronal dysfunction and death. In some early in vitro cell studies, bosutinib demonstrated the ability to reduce TDP-43 aggregate formation to a certain extent. This provides theoretical support for its “drug repurposing” strategy that extends from traditional TKIs to neurodegenerative diseases.

Despite this, the current clinical research of bosutinib forALS is still in a very early stage, with only a few exploratory small-sample clinical trials and case observations. For example, some overseas research institutions are conducting feasibility and safety trials of bosutinib in ALS patients, trying to evaluate its role in motor neuron protection. Some results indicate that patients are tolerable to the drug, but its substantial delaying effect on the disease process still needs to be verified by evidence of larger-scale, long-term follow-up. At this stage, no mainstream neurological guidelines recommend it as a first-line or auxiliary drug for ALS.

In treatmentWithin the overall framework of ALS, the introduction of any potential new drugs must consider their multidimensional effects on respiratory function, motor ability, swallowing system, and cognitive status. Although bosutinib provides some possible target-modulating advantages in mechanism, its side effects as an anti-cancer drug, including gastrointestinal discomfort, elevated liver enzymes, risk of infection, etc., may bring additional risks in this already vulnerable patient group of ALS. Therefore, a comprehensive assessment of the risk-benefit ratio is particularly critical.

Reference materials:https://go.drugbank.com/drugs/DB06616