The effect of Bosutinib on ALS

Bosutinib is a tyrosine kinase inhibitor that was originally developed and used to treat chronic myelogenous leukemia (CML). Its core mechanism of action is to inhibit BCR-ABL kinase activity, thereby blocking abnormal signaling in cancer cells. However, in recent years, researchers in the field of neuroscience have discovered that this drug is receiving attention for its potential role in neurodegenerative diseases, especially amyotrophic lateral sclerosis (ALS).

ALS, commonly known as "ALS", is a progressive and fatal motor neuron disease in which patients lose motor function due to the gradual degeneration of neurons. Traditional treatments mainly focus on delaying disease progression, such as drugs such as riluzole and edaravone, but their efficacy is still limited. The key reason why bosutinib has received renewed attention is that it can inhibit the Src/c-Abl pathway, which has been proven to be closely related to neuronal apoptosis and neuroinflammatory responses. Studies have shown that c-Abl protein kinase activity is abnormally elevated in ALS models, leading to TDP-43 protein aggregation, and this protein aggregation is one of the pathological characteristics of ALS. By inhibiting c-Abl activity, bosutinib helps reduce neuronal damage, improve cellular energy metabolism and reduce inflammation levels, thereby theoretically delaying the neurodegeneration process.

The results of an early Phase I clinical trial showed that bosutinib showed good safety and tolerability in ALS patients, with no serious side effects, providing confidence for subsequent expansion of research. Although it has not yet received formal indication approval for ALS, this exploration of "new uses of old drugs" shows new ideas for targeting molecular mechanisms in neurodegenerative diseases. It is worth noting that the pharmacokinetic characteristics of bosutinib enable it to have good brain penetration, which provides a basis for the treatment of central nervous system diseases. If subsequent clinical trials confirm that bosutinib can delay the progression of ALS, it will mean that existing anti-cancer targeted drugs are expected to achieve cross-border breakthroughs in the field of neurological diseases.

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