Abstract Details

Title A Pilot, Randomized, Placebo-Controlled, Trial of Lithium in Spinocerebellar Ataxia Type 2

Topic Movement Disorders

Presentation(s) S43 - (-)

Poster/Presentation
Number 005

Objective

Background SCA2 is caused by the expansion of a CAG trinucleotide in the ataxin-2 gene. Mutated ataxin-2 facilitates Ca2+ release from the inositol-1,4,5-triphosphate receptor (InsP3R1). Treatment of the SCA2 mouse model with Dantrolene, a Ca2+ signal stabilizer, improves motor performance and Purkinje cell loss. Pathological cytoplasmic inclusions, containing ataxin-2, are present in SCA2. Lithium is able to stimulate autophagy and to clear protein aggregates. Lithium also reduces IP3 levels, and subsequent Ca2+ efflux from the InsP3R1.

Design/Methods We designed a double-blind, placebo-controlled, randomized pilot clinical trial of 48 weeks with lithium in SCA2. Lithium was administered twice-daily to a max dose of 1500 mg/day with a serum target level of 0.9-1.2 mMol/L. Clinical progression was measured with the Scale for the Assessment and Rating of Ataxias (SARA), depression with the Beck's Depression Inventory (BDI-II), quality of life with the EQ-5D.

Results Twenty patients were enrolled, 17 randomized (9M, 8F), 9 received lithium, 8 placebo. 40 adverse events (AEs) were reported during the trial, 28 in the lithium group and 12 in the placebo (p = 0.11). Mean AE duration was 57.4±60.8 and 77.4±68.5 days (p= 0.37). Main AEs in the lithium group were headache, constipation, polyuria, polydipsia, TSH increase. Mean SARA worsening was 0.25 for the lithium and 0.75 points for the placebo group, BDI-II improved 8.9 and 2.6, and the EQ-5D worsened 8.1 and 3.1 points (p=NS).

Conclusions Lithium was well tolerated and reported AEs were similar to those previously described for bipolar disorder patients. Although not significant, secondary endpoints are in favor of the lithium group. A correctly powered phase III trail is needed to assess if lithium may slow disease progression in SCA2.

Authors/Disclosures
Francesco Sacca, MD, FAAN (University Federico II) PRESENTER	Dr. Sacca has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Alexion. Dr. Sacca has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Argenx. Dr. Sacca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lexeo. Dr. Sacca has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. Dr. Sacca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genpharm. Dr. Sacca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Sacca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medpharma. Dr. Sacca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Madison Pharma. Dr. Sacca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Zai Lab. Dr. Sacca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Dianthus. Dr. Sacca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Reata. Dr. Sacca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sandoz. Dr. Sacca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neopharm Israel. Dr. Sacca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Johnson&Johnson. Dr. Sacca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. Dr. Sacca has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Astrazeneca. The institution of Dr. Sacca has received research support from AIFA. The institution of Dr. Sacca has received research support from FARA.
Angela Marsili	Angela Marsili has nothing to disclose.
Chiara Pane, MD	Dr. Pane has nothing to disclose.
	No disclosure on file
Giuseppe De Michele, MD	No disclosure on file
Giorgia Puorro	Giorgia Puorro has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Elma Research. Giorgia Puorro has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Alexion.
Mario Quarantelli, MD (CNR Edificio 10)	No disclosure on file
	No disclosure on file
Elena Salvatore, MD	No disclosure on file
Alessandro Filla, MD, FAAN	No disclosure on file
Massimo Filippi, MD, FAAN (Ospedale San Raffaele, Neuroimaging Research Unit)	Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alexion, Almirall, Biogen, Merck, Novartis, Roche, Sanofi. Dr. Filippi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion, Biogen, Bristol-Myers Squibb, Merck, Novartis, Roche, Sanofi, Sanofi-Aventis, Sanofi-Genzyme, Takeda. Dr. Filippi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bayer, Biogen, Celgene, Chiesi Italia SpA, Eli Lilly, Genzyme, Janssen, Merck-Serono, Neopharmed Gentili, Novartis, Novo Nordisk, Roche, Sanofi, Takeda, and TEVA. Dr. Filippi has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer Nature. The institution of Dr. Filippi has received research support from Biogen Idec, Merck-Serono, Novartis, Roche, the Italian Ministry of Health, the Italian Ministry of University and Research, and Fondazione Italiana Sclerosi Multipla.

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