Mass General team presents mouse data to back the case for using reformulated asthma drug to treat ALS
Can a reformulation of an old drug on the market for asthma, allergy and mastocytosis protect against liver disease, Alzheimer’s, and amyotrophic lateral sclerosis?
A team from Massachusetts General Hospital is making a case for the latter two. Having recently found an injection of cromolyn sodium effective in inhibiting amyloid beta (Aβ) aggregation in vitro and in mouse models, researchers set out to investigate whether the same compound can achieve the same in ALS.
Their conclusion, published on Nature’s open access journal Scientific Reports:
Our results indicate that cromolyn sodium treatment significantly delayed the onset of neurological symptoms, and improved deficits in PaGE performance in both male and female mice, however, there was only an effect on survival in female mice.
While the precise etiology of ALS remains poorly understood, one theory proposes that neuroinflammatory processes are implicated in its initiation and progression.
As cromolyn inhibits mast cell degranulation, the scientists at Mass General hypothesized that it could convert immune cells in the brain, including microglia and astrocytes, from a pro-inflammatory to an anti-inflammatory state as well as reducing the levels of cytokines and chemokines.
After comparing the effects of once-daily injections of cromolyn versus a placebo in wild type mice and mice carrying a genetic mutation for ALS, respectively, the researchers came up empty on the microglia and astrocytes theory. But they did find lower levels of pro-inflammatory cytokines/chemokines in the spinal cord and plasma — in addition to observing that the transgenic mice treated with cromolyn sodium had the highest motor neuron counts among the four groups.
“Our study supports the notion that inflammation has a significant role in the progression of ALS and therefore exploring anti-inflammatory treatments may be of great value for developing an effective treatment,” said Ghazaleh Sadri-Vakili, lead author of the study and director of the NeuroEpigenetics Laboratory at Mass General, in a statement.
Sadri-Vakili has previously noted that the neurology department at Mass General has a plan in place to get the drug — provided by AZTherapies — into the clinic for ALS.
Unlike the formulations of cromolyn currently available through prescription and over the counter, which are absorbed through lung and nasal inhalation or ingested drops, the version injected into mice in the study can be “fully available in the bloodstream” and cerebrospinal fluid, according to the biotech.
AZTherapies is conducting a Phase III trial of another formulation of cromolyn, combined with oral ibuprofen, to treat early Alzheimer’s. It is unclear whether any clinical programs are in place to test cromolyn sodium in primary sclerosing cholangitis after Baylor Scott and White Health researchers reported it decreased biliary proliferation and fibrosis in mice.