Friday, May 4, 2007
Effectiveness of Anti-androgen Therapy for Spinobulbar Muscular Atrophy (SBMA): An Open Study of 4 Cases for 3 Years
Yusuke Niimi, Kinya Ishikawa, Masanaga Yamawaki, Hidehiro Mizusawa, Tokyo, Japan
OBJECTIVE: To clarify the effect of anti-androgen therapy in patients with SBMA. BACKGROUND: Spinobulbar muscular atrophy (SBMA) is an adult-onset, X-linked recessive motor neuron disease caused by an expansion of a trinucleotide CAG repeat that encode polyglutamine tract in the androgen receptor (AR) gene. The pathogenic mechanism of this disease is recapitulated in mice by overexpressing the human AR gene with expanded CAG repeat. In addition, disease progression as well as formation of polyglutamine inclusion in vivo was suppressed in the transgenic mice by administering leutenizing hormone-releasing hormone (LH-RH) analog, which interferes mutant AR protein to accumulate in the nucleus of cells. DESIGN/METHODS: After approved by the institutional review board, we prospectively studied clinical efficacy of goserelin (Zoladex LA), a LH-RH analog, in 4 patients with SBMA with an open study manner. The study was undertaken for four years from, September, 2002 to October, 2006. Goserelin was subcutaneously injected every 3 month regularly to maintain the drug concentration. We evaluated the clinical manifestations by manual muscle testing (MMT), micro-FET, serum CK and ALT, and nerve conduction study. Changes of polyglutamine inclusion densities in the epidermis of the scrotum were assessed by immunohsitochemistry using anti-polyglutamine antibody 1C2, before and after the therapy. RESULTS: Clinically, effect of goserelin was seen by strength. The muscle strength showed 28% increase after the therapy. In nerve conduction study, median nerve CMAP improved 23%. Three out of four patients showed improvement in any of the parameters. In relationship with the disease severity, the goserelin was the most effective in patients with early stage of illness. The density of polyglutamine-inclusion in the epidermis of the scrotum did not change significantly. CONCLUSIONS/RELEVANCE: Anti-androgen therapy with LH-RH analog may inhibit disease progression especially in the early stage. A study recruiting a larger number of patients is needed to confirm the efficacy of this agent.
Category - Neurogenetics and Gene Therapy
SubCategory - Therapeutics
March 20, 2007
KDA Funded Research Update
Chawnshang Chang, Ph.D. and a team of researchers at the University of Rochester Medical Center have published the attached news release concerning their research that could potentially lead to a treatment for Kennedy's Disease. The article was published in the March 6 issue of the journal Nature Medicine.
Thanks to the generous support of our associates, Dr. Chang received a $25,000 research grant from the Kennedy's Disease Association last fall.