LTI is leveraging its expertise in lysosomal biology to develop novel small molecules to be used in the treatment of various neurodegenerative diseases. Our lead candidate, LTI-291, is being developed as a potential treatment for GBA-associated parkinsonism (GBA-AP). Existing therapies and treatments for Parkinson’s disease provide transient symptomatic benefits, but do not address the underlying disease process which drives disease progression.
With the help of an initial grant from the Michael J. Fox Foundation, LTI has started characterizing GBA1-mutation carrying PD patients. LTI is also investigating the composition of glycosphingolipids in blood from PD patients to determine whether such a “fingerprint” could serve as a predictive biomarker for identifying Parkinson's disease patients that are likely to respond to LTI-291 or our other therapeutic drug candidates.
There is a high, unmet medical need for treatment of the fundamental causes of Parkinson’s disease and GBA-AP. Rather than merely providing symptomatic relief, therapies targeting the underlying biological causes of Parkinson’s disease could potentially slow disease progression in this condition.
A Targeted Approach
There is a high, unmet need for medicines which address the fundamental causes of Parkinson’s disease and GBA-AP. Rather than merely providing symptomatic relief, therapies targeting the underlying biological causes could potentially slow disease progression for certain patients.
For GBA-AP patients with compromised GCase enzymatic activity, several lines of evidence suggest that pharmacological activation of the GCase enzyme could provide therapeutic benefits. LTI-291 is the first activator of the GCase enzyme to enter clinical studies and is under development by LTI as a novel, first-in-class drug compound for the potential treatment of patients with GBA-AP.
LTI-291 is designed to target the GCase enzyme, increasing its activity, and therefore reducing its substrate, Glucosylceramide (GluCer). High levels of GluCer have been postulated to be harmful and associated with disease. Preclinical studies have shown that LTI-291 easily crosses the blood-brain-barrier and accesses the GCase enzyme within the brain and central nervous system.
Studies in several animal models with compromised GCase activity have shown that administration of LTI-291 leads to reduction of GluCer levels in the brain. In fact, the GluCer-lowering effect of LTI-291 mediated GCase activation is more profound when GCase enzyme activity is more impaired and GluCer levels are higher. LTI-291 is able to normalize GluCer levels in a number of model systems.
Studies in human cell lines, including fibroblasts and pluripotent neuronal stem cells, as well as in various animal studies, have shown that LTI-291 has an excellent efficacy, safety and toxicity profile, warranting its further testing and positioning it for clinical development.