Disease modifying therapy for multiple system atrophy – Parkinsonian Type

Abstract

BACKGROUND: Multiple System Atrophy –Parkinsonian Type (MSA-P) is a rare, rapidly progressive neurodegenerative disease without any current treatment. Recent research has increased the understanding of brain iron accumulation and its association with neurodegenerative synucleinopathies, like MSA-P. Because of this improved understanding of the disease process, there is potential for new therapies that could benefit patients with MSA-P. Unfortunately, many attempts at finding a new and effective treatments for MSA-P have been unsuccessful. Two drugs that have shown potential in neurodegenerative synucleinopathies associated with brain iron accumulation are iron chelators (Deferiprone) and tyrosine kinase inhibitors (Nilotinib.) METHODS: The proposed study is a multicenter, double blind, randomized control study of Nilotinib and Deferiprone for the treatment of MSA-P. There will be two treatment arms; Nilotinib and a placebo group vs. Nilotinib and Deferiprone. There will be a 24 week treatment phase, followed by a 24 week wash-out phase. All patients will have a baseline evaluation including: a full neurological exam with rating scales (UMSARS, UPDRS, SCOPA, and MOCA) to assess motor and non-motor symptoms of MSA-P. Lab and imaging data will include CBC, CMP, serum iron panel, CSF iron panel and brain SWI-MR scans. Neurological exams and rating scales will be assessed every four weeks while imaging and laboratory data will be assessed at baseline (week 0) at the end of the intervention phase (week 24) and at the end of the follow-up phase (week 48). CONCLUSIONS: Deferiprone and Nilotinib when used together will have a synergistic impact on the symptoms of MSA-P and will be more effective when used together versus when they are used individually. SIGNIFICANCE: Patients with MSA-P have shortened life expectancy as well as severely diminished quality of life due to rapidly progressive neurodegeneration. This trial aims to implementing evidence based treatment for MSA-P that could potentially improve life expectancy as well as quality of life in this patient population