Leuprorelin acetate may be a promising therapy to minimize swallowing dysfunction in patients with spinal and bulbar muscular atrophy (SBMA), a study finds.
The study, “Efficacy and safety of leuprorelin acetate for subjects with spinal and bulbar muscular atrophy: pooled analyses of two randomized-controlled trials,” was published in the Journal of Neurology.
SBMA, also known as Kennedy’s disease, is a type of spinal muscular atrophy (SMA) that starts in adulthood and is characterized by widespread muscle weakness and wasting in the arms, legs, head, and neck (bulbar involvement). For this reason, besides having impaired mobility, SBMA patients may have difficulties swallowing and speaking.
The disorder is caused by mutations in the androgen receptor (AR) gene — located on the X chromosome — which provides instructions for the androgen receptor protein. Although this protein is present everywhere in the body, it is enriched in motor neurons, the nerve cells responsible for controlling voluntary movements that are gradually destroyed in patients with SMA.
Because the the AR gene affects the body’s response to androgens — the male hormones involved in sexual development, such as testosterone — patients may have other symptoms, including infertility and erectile dysfunction (male impotence).
After the discovery of the AR gene, studies in animal models of disease revealed SBMA is triggered by the interaction of androgens with the defective androgen receptors. For this reason, treatment for SBMA has centered on the development of therapies involving androgen deprivation.
“Successful treatment of SBMA in mouse models with castration or administration of leuprorelin acetate, a luteinizing hormone-releasing hormone (LH-RH) agonist that reduces testosterone release from testes, supported the idea that testosterone blockade therapy could be beneficial and enabled subsequent human clinical trials,” the study stated.
In the study, Japanese researchers performed a pooled analysis of two identical randomized, placebo-controlled, double-blind clinical trials — JASMITT-06DB and JASMITT-11DB — to evaluate in more detail the efficacy and safety of leuprorelin acetate in patients with SBMA.
In both trials, patients were randomly assigned to receive either leuprorelin acetate or a placebo (control), once every 12 weeks, for 48 weeks. The primary goal was to assess changes in the amount of barium residues (a contrast agent used to visualize structures in the body) in the pharynx (throat) when patients attempted to swallow. Secondary measures included blood tests to measure testosterone levels, scrotal skin biopsies, and quality of life assessments.
In total, 283 SBMA patients were enrolled, including 142 who were treated with leuprorelin acetate and 141 with placebo.
Patients treated with leuprorelin acetate and those treated with placebo had an average decrease of 4.12% in the amount of barium residues present in the pharynx after initial swallowing. Although differences between the two groups after initial swallowing suggested that leuprorelin acetate might be effective at each assessment point, the changes from the initial visit to the last were not statistically significant between both groups, and the primary objective was not reached.
In general, leuprorelin acetate treatment was well-tolerated. The incidence of side effects (81.7% taking leuprorelin and 80.1% in the placebo group) and drug-related side effects (62.7% taking leuprorelin and 53.9% in the placebo group) were similar between the two groups.
However, some of the side effects, including abnormal liver function, weight gain, skin reactions at the injection site, decreased libido, erectile dysfunction, and excessive sweating, were more severe in patients treated with leuprorelin acetate than in those treated with placebo.
“In conclusion, leuprorelin acetate may be safe and beneficial for improvement of swallowing dysfunction in the patients with SBMA, without increasing the number of serious side effects,” the researachers said. “Further investigations are needed to clarify the efficacy of this therapy for SBMA.”