The findings, “Cancer Drug Repurposing for Treating Amyotrophic Lateral Sclerosis (ALS),” were presented at the 2019 American Academy of Neurology (AAN) annual meeting, taking place through May 10 in Philadelphia.
Repurposing existing medications — particularly those approved by regulatory bodies such as the U.S. Food and Drug Administration and the European Medicines Agency — has a number of benefits. Most notably, solid data on the safety of the treatment usually already exists through previous studies done in humans.
A type of cancer therapy called a tyrosine kinase inhibitor (TKI) — which, as the name suggests, work by inhibiting tyrosine kinases, a protein involved in many cellular signaling processes — can promote the growth of brain cells. This has piqued interest in these medications as possible therapeutics for neurodegenerative diseases, including ALS.
This led researchers to test four of these TKIs — imatinib mesylate, dasatinib (sold under the brand name Sprycel), bosutinib (brand name Bosulif), and nilotinib (brand name Tasigna) — in cellular models of ALS. All of these therapies target similar proteins and are all used to treat different types of leukemia.
These four treatments were tested in cells with an ALS-causing mutation, known as G93A-SOD1, in the SOD1 gene. Imatinib mesylate — but none of the other tested compounds — decreased the amount of G93A-SOD1 protein that these cells produced, suggesting that this therapy might have beneficial effects in ALS.
Based on these findings, the researchers used imatinib mesylate to treat 12–14 mice with modeled ALS caused by the same G93A-SOD1 mutation. The animals were treated with 2.5 mg/kg of the compound daily, beginning at 60 days old, approximately 30 days before disease symptoms.
They reported that the treatment significantly delayed the start of the disease (onset of tremor), and treated mice lived longer than untreated ones.
This treatment also “provided improvements in progression,” which was measured by observed paralysis in the animals.
The 2.5 mg/kg dosage used in the mice corresponds to 188 mg per day in an adult weighing 75 kilograms (about 165 pounds). This dose is comparable to the dose that would be given for a human undergoing cancer treatment (200–800 mg per day). Furthermore, imatinib mesylate can be taken orally and can penetrate the blood-brain barrier.
This suggests that this therapy, already approved to treat cancer, could be repurposed for ALS treatment — though, of course, further studies will be needed to determine whether it has any significant benefit for human ALS patients as well as the optimal dose.
“Consequences of long-term treatments and potential side effects also need to be considered,” the researchers said in the presentation’s conclusions.