Evidence suggests that the gut microbiome may play a role in susceptibility to various diseases, including those affecting the brain. Probiotics are friendly, live bacteria that benefit the digestive system and are being explored for their potential effects on a range of diseases, including obesity, colorectal cancer, cardiovascular disease, and ALS. In worm models of ALS, the probiotic formulation Lacticaseibacillus rhamnosus HA-114 was shown to help prevent neurodegeneration and appeared to aid lipid metabolism within cells. Proper lipid metabolism is crucial for maintaining normal cellular energy levels and function. Further work confirmed the effects in ALS model mice before moving to human clinical trials. This Phase 2 study will recruit 150 participants, who will be randomly assigned to receive either the dietary supplement PROBIO_HA114 or a placebo orally for 24 weeks. The study will evaluate the safety and effectiveness of PROBIO_HA114 by measuring changes in a variety of biological measures, such as lipidomic and metabolite profiles, as well as the ALS Functional Rating Scale-Revised (ALSFRS-R) score.
Abnormalities in a protein called TDP-43 are present in approximately 97 percent of all ALS cases. Preclinical studies have shown that when the amount of functional TDP-43 is decreased within cells, the level of another protein, STMN2, is substantially decreased. Patient tissues analyzed by researchers also showed that STMN2 levels are lower than expected specifically in motor neurons. These findings support the idea that a reduction in STMN2 resulting from TDP-43 dysfunction contributes to ALS and suggest that methods to preserve the levels of STMN2 within motor neurons may have a therapeutic benefit. QRL-201 is a genetically targeted therapy that aims to restore normal STMN2 levels in people living with ALS. This Phase 1 study will enroll 64 participants who will be randomly assigned to have either the active drug (QRL-201) or placebo delivered into the spinal fluid through a procedure known as an intrathecal injection. Researchers will monitor participants to ensure that the drug is safe, determine the appropriate dosage, and learn more about how the body breaks down the drug internally.