Development of Phospho-c-abl and Phospho-CRKL Assays for Use as Nilotinib Companion Diagnostics in Parkinson’s Disease
Evidence suggests that increased activity of c-abl in the brain may contribute to the development and progression of Parkinson’s disease. Nilotinib, a drug that inhibits c-abl, has recently shown promise as a potential therapeutic. In its activated state, c-abl is modified with a phosphate group at specific amino acids and measuring the extent of phosphorylation may be an effective method of determining whether Nilotinib is working for a given patient. Unfortunately, researchers have not yet been able to detect these specific phosphorylation sites due to the low concentration of these proteins in cerebrospinal fluid. In order to effectively monitor Nilotinib in clinical trials, it is necessary to develop a test that can measure these phosphorylated proteins at low concentrations.
Our lab is working create assays to measure the phosphorylation state of c-abl and its downstream target CRKL using a high sensitivity technology called Simoa. We hypothesize that using this new technique we will be able to measure specific phosphorylation states that have not previously been detected.
We believe our assays will be instrumental in assessing the efficacy of Nilotinib in clinical trials, and in the future these assays could become a companion diagnostic for the drug. The tests we develop might inform doctors in advance which patients will be most likely to benefit from Nilotinib, and it may even allow them to tailor the dosage of the drug in response to ongoing chemical changes in their patient’s brain.
After completion of this study, if successful, these tests will be made available to the research community and used in upcoming clinical trials. If it is found that administering these tests allows doctors to better select patients for Nilotinib treatment, the tests will be made commercially available for this purpose.