Abstract Details

Title A Pilot Trial of Clenbuterol in Spinal and Bulbar Muscular Atrophy

Topic Anterior Horn

Presentation(s) S36 - (-)

Poster/Presentation
Number 003

Objective

Background SBMA is an adult-onset, X-linked, lower motor neuron disease, characterized by slowly progressive muscle weakness and atrophy. The disease is caused by an expansion of a CAG repeat encoding a polyglutamine tract within the androgen receptor (AR) gene. Clenbuterol is a beta2-agonist which is well known to induce muscle hypertrophy. The anabolic effects of clenbuterol implicate the activation of the PI3K/Akt signaling. Recently, phosphorylation of AR by Akt in skeletal muscle of a SBMA mouse model has been shown to block ligand-dependent nuclear translocation of AR, leading to a rescue of disease phenotype.

Design/Methods Twenty SBMA patients were given oral clenbuterol (0.02 mg twice a day) for 1 year. Primary outcome measure was the walk distance improvement evaluated according to the 6-minute walk test (6MWT) at 12 months. 6MWT is a reliable biomarker to monitor progression of motor impairment in SBMA; it significantly decreases at a rate of 11.3% per year. Secondary outcome measure was the over time change of the following variables: MRC and ALSFRS-R score, fVC % values. Safety was assessed by laboratory tests and report of adverse events.

Results Sixteen SBMA patients completed the study. 6MWT significantly increased at 3 months and remained unchanged throughout the entire study period until the study end when it still measured significantly higher relative to baseline (p<0.0009). A significant sustained improvement of fVC % values was also observed (p= 0,01). ALSFRS-R and MRC score did not change over the study period. Clenbuterol was generally well tolerated. No major effect on heart function or rhythm was reported.

Conclusions Our data suggest that clenbuterol may have a role in treating SBMA.

Authors/Disclosures
PRESENTER	No disclosure on file
	No disclosure on file
Wolfgang Walter Feneberg, MD (Marianne Strauss Klinik)	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Letizia Mazzini	No disclosure on file
Vincenzo Silani, MD, FAAN (University of Milan Medical School - IRCCS Istituto Auxologico Italiano)	Dr. Silani has nothing to disclose.
Jessica Mandrioli	No disclosure on file
Monika Raimondi, MD	No disclosure on file
Corrado Angelini, MD, FAAN (Università Di Padova)	Dr. Angelini has nothing to disclose.
Elena Pegoraro, MD, PhD (University of Padova)	No disclosure on file
	No disclosure on file

��ɫ��

��ɫ��