Objective: To evaluate the safety and potential efficacy of RE-024 in open treatment of 2 patients with PKAN.

Background: PKAN is an autosomal recessive, neurodegenerative disorder of progressive parkinsonism and dystonia, caused by a defective PanK2 enzyme, the rate limiting step in Coenzyme A production. RE-024 is designed to bypass this defect.

Methods: Two sibling males with PKAN ages 24 (patient 1) and 29 (patient 2) have been treated with RE-024 for 47 weeks. Patient 1 presented at age 10 with frequent falls, progressing to dystonia, dysphagia, cognitive decline, and eventually deteriorating ADLs. By age 20 he was unable to walk except with strong physical support. Patient 2 presented with frequent falls and hand dystonia at age 10, progressing to severe generalized dystonia, dysphagia, and dysarthria by age 18, and deteriorating ADLs. He eventually became bed and wheelchair-bound and anarthric, and required gastric tube feeding by age 26. PKAN was diagnosed by clinical presentation, MRI (“eye-of-the-tiger sign”) and genetic testing at ages 20 and 24 years, respectively. After approval from national and local authorities, oral RE-024 was increased over 5 days to 180mg and 120mg daily, respectively (given TID). Safety monitoring and scale assessments of dystonia, parkinsonism and quality of life were conducted.

Results: Patients 1 and 2 improved as follows:

Conclusions: Oral RE-024 treatment was associated with clinically meaningful improvement in uncontrolled, open treatment of 2 patients with moderate to severe PKAN at baseline over a 47 week period. Controlled clinical trials should evaluate the safety and efficacy of RE-024 in patients with PKAN.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/re-024-a-potential-phosphopantothenate-replacement-therapy-in-2-patients-with-pantothenate-kinase-associated-neurodegeneration-pkan/