Spinal and bulbar muscular atrophy (SBMA) is a motor neuron disease characterized by slowly progressive muscle weakness and atrophy of bulbar, facial and limb muscles. The onset of weakness is usually between 30 and 60 years followed by a slow progression of neuromuscular symptoms. Bulbar palsy often aggravates in the advanced stage of this disease, resulting in life-threatening respiratory tract infections and eventual early death. To date, no curative therapy has been established for SBMA. The cause of SBMA is expansion of a trinucleotide CAG repeat, which encodes the polyglutamine tract, in the first exon of the androgen receptor (AR) gene. SBMA mainly occurs in adult males, whereas neurological symptoms are rarely detected in females having a mutant AR gene. Leuprorelin, an LHRH (luteinizing hormone-releasing hormone) agonist that reduces testosterone release from the testis, has previously been shown to suppress nuclear accumulation of mutant AR, leading to rescue of motor dysfunction in male SBMA mice. In this paper, a team of Japanese researchers has evaluated the efficacy of treatment with leuprorelin acetate in 50 SBMA patients in a preliminary clinical trial. The trial lasted 48 weeks and was followed by an open-label treatment in 34 patients for an additional 96 weeks. Leuprorelin significantly inhibited accumulation of pathogenic AR protein in the scrotal skin of patients, significantly decreased the level of serum creatine kinase, and suppressed the progression of dysphagia, suggesting that hormonal intervention with LHRH agonist is capable of interfering with the central pathogenesis of SBMA.

Références : Ann Neurol. 2009 Feb;65(2):140-50.