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Joanie McGuire sent me this abstract from the recent Neuroscience conference. it answers concerns I had re heart problems/sudden death at high doses. People with QTc were excluded from the trial. Abstract: Parkinson’s disease is characterized by loss of dopamine neurons and accumulation of α-Synuclein in LBs. Nilotinib is a potent inhibitor of Abl tyrosine kinase and it is FDA-approved for adult CML. Nilotinib penetrates the brain and inhibits Abl, leading to autophagic clearance of amyloid proteins. It also increased brain dopamine and modulated immune markers, and reversed motor and cognitive decline. We conducted a clinical trial with the primary objective to determine the safety and efficacy of Nilotinib in advanced PD, PDD and LBD patients. Our studies include measurement of CSF and plasma biomarkers at baseline, 2 and 6 months with 150mg and 300mg Nilotinib daily. These doses are significantly lower of Nilotinib for CML treatment (800-1200mg/ day). We excluded patients with prolonged QTc and other medical contradictions. 8 patients have passed the 2 months period. More than half the patients screened were excluded due to cardiac complications. Nilotinib has a good safety profile in enrolled subjects with no QTc prolongation or myelosuppression. Nilotinib CSF penetration is 0.5-1.5%. A significant reduction (>60%) in plasma α-Synuclein was detected, correlating more frequent bowel movements. There is also a significant decrease in CSF p-Tau181, while total Tau is unchanged. CSF Abeta40 is reduced (18%) with no change in the plasma, while CSF and plasma Abeta42 remain stable. The level of CSF α-Synuclein is unchanged, suggesting stabilization of α-Synuclein levels. CSF homovanillic acid (HVA) is reduced (26%) at 2 months despite a decrease in dopamine replacement therapy, suggesting inhibition of dopamine breakdown. This effect on dopamine also correlates with clinical outcomes, including stabilization with less or no Azilect and L-Dopa. Nilotinib also increases CSF concentration (30-55%) of neuro-restorative markers (PDGF-AB/BB, G-CSF, IL-7, GRO, CCL2 and CCL5), while it reduces markers of neurodegeneration (NSE and S100B). Overall these data indicate safety, tolerability and biomarkers efficacy, and provide a collectively compelling rationale to examine Nilotinib in larger placebo-controlled, double blind studies in earlier stages of diseases. Ray Rayilyn Brown Past Director AZNPF Arizona Chapter National Parkinson Foundation ---------------------------------------------------------------------- To sign-off Parkinsn send a message to: mailto:[log in to unmask] In the body of the message put: signoff parkinsn