GSNOR Inhibition for Treatment of Parkinsonís Disease
Rapid Response Innovation Awards, 2014
Study Rationale: † † † † † † † † † †
Parkinsonís disease may be driven by inflammation and toxic, reactive products from oxygen metabolism. SAJE Pharmaís drugs target an enzyme called s-nitrosoglutathione reductase (GSNOR) to inhibit both of those toxic processes, which may slow Parkinsonís progression.†
SAJE Pharma seeks to learn if its drug can enter the brain and can inhibit Parkinsonís in a pre-clinical disease model.
SAJE Pharma will first determine which of its drugs are predicted by a computer model to enter the brain and then measure whether those drugs do, in fact, enter the brain. The best of those brain-entering drugs will be tested in a model of Parkinsonís disease to evaluate its impact.
Impact on Diagnosis/Treatment of Parkinsonís Disease: † † † † † † † ††
If our study proves that one of our drugs can inhibit Parkinsonís disease in a pre-clinical model, we will have a reason to move toward clinical testing of this potential treatment for the disease.
Next Steps for Development:
If this study is successful, we will need to confirm it in a second pre-clinical study. If that study is also successful, we will then start toxicity and safety studies to get the drug ready for clinical trials with Parkinsonís patients.
Although oxygen and nitrogen are the essential elements of every living cell, they can assume a harmful form and damage the cell. This is especially common in inflammation and disease, including Parkinson's disease (PD). By supporting this process, an enzyme called s-nitrosoglutathione reductase (GSNOR) aggravates the disease. GSNOR inhibitors -- drugs that slow down or turn off GSNOR -- can slow or stop the damage. In this study, we aimed to evaluate the ability of one of such inhibitors to slow disease progression in pre-clinical models of Parkinson's.
We tested the ability of SPL-334, a GSNOR inhibitor, to travel to the brain and stay there to exert its therapeutic effect in PD. We found that the drug did not travel to the brain in high enough quantities nor did it stay there long enough to treat PD. We then developed 11 other potential GSNOR inhibitors and found one that strongly inhibited GSNOR and was predicted to pass into the brain. We have produced a quantity of it sufficient to complete future studies.
Chairman, President and Chief Technical Officer at SAJE Pharma, LLC
Location: Baltimore, Maryland, United States