Research into Kennedy’s Disease
Research into Kennedy’s Disease
Page last updated 28th November 2022
For information on the symptoms and support, see our page: SBMA-Kennedy’s and the KDUK website.
Of the non-5q SMAs, the most research has been carried out into Kennedy’s disease. In 2015, an ENMC (European Neuromuscular Centre) workshop was held on the condition, with experts from around the world discussing research that has been undertaken into Kennedy’s disease. Of the many recommendations that were put forward, establishment of an international patient registry was suggested to facilitate research.
One of the main ways Kennedy’s disease differs from 5q SMA is in the effects on the hormonal receptors. It has long been hypothesised that this could be an avenue for potential treatment. Following successful studies on animals, and smaller clinical trials with successful results2, Katsuno and colleagues performed a study looking at the medicine ‘leuprorelin’3. This treatment aimed to suppress the hormone receptors, which were thought to be contributing to the condition, via reducing testosterone production in the testicles. In spite of a well performed, large study that included a strong trial design with randomisation of 199 participants and use of a placebo, the individuals failed to show any improvement in the most important outcome, which was measurement of swallowing ability3. However, the study did show some positive effects, although these were not found in all treated participants; they were limited to those who had developed symptoms within the previous ten years. Therefore, it may be that the medicine works better on individuals who are earlier in the disease course4.
Dutasteride is another medicine that has been investigated in clinical trials for Kennedy’s disease, and this also aims to alter testosterone function. The aim of this medicine is to retain the beneficial effects of testosterone on muscle, whilst reducing the form of testosterone that contributes to the disease. Fernandez-Rhodes and colleagues enrolled 50 individuals for a two-year period of treatment or placebo5. Similar to the study of Katsuno and colleagues, dutasteride had no significant effect on the most important outcome measure, although there were some positive effects in other assessments5. The failure of the trial to identify a significant difference between the two groups may have been due to the design; there may have been too few participants and the trial may have been too short for such a slowly progressive condition as Kennedy’s disease.
Clenbuterol has also been looked into as a treatment for Kennedy’s disease, it is a medicine usually given to treat asthma, but is thought to have beneficial effects on muscle. Querin and colleagues followed 16 participants over a one-year period, and found that walking distance in six minutes and breathing, were significantly better in those who were treated. Other measurements of how the condition progresses, such as strength and questionnaires, were not significantly different6.
Exercise may be beneficial in some muscle problems, although originally it was believed to be detrimental due to the risk of increasing muscle damage. A trial that asked participants with Kennedy’s disease to cycle on a special exercise bike showed no beneficial effects in terms of breathing tests7. A more recent trial looked at 50 men who took part in an exercise program of either stretching only, or a series of exercises that increased in intensity each week. They found that some participants experienced beneficial effects, although overall the measurements of muscle strength and function were not significantly different between the two groups. This could be due to the choice of participants, with potential for greater effects in those who were younger and less severely affected, as well as insufficient intensity of exercise8.
1. Pennuto et al. (2015) 210th ENMC International Workshop: Research and clinical management of patients with spinal and bulbar muscular atrophy, 27–29 March, 2015, Naarden, The Netherlands. Neuromuscul Disord 25: 802-812.
2. Banno et al. (2009) Phase 2 trial of leuprorelin in patients with spinal and bulbar muscular atrophy. Annal Neurol 65: 140-150.
3. Katsuno et al. (2010) Efficacy and safety of leuprorelin in patients with spinal and bulbar muscular atrophy (JASMITT study): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet Neurol 9: 875-884.
4. Weydt et al. (2016) Clinical Trials in Spinal and Bulbar Muscular Atrophy-Past, Present, and Future. J Mol Neurosci 58: 379-387.
5. Fernandez-Rhodes et al. (2011) Efficacy and safety of dutasteride in patients with spinal and bulbar muscular atrophy: a randomised placebo-controlled trial. Lancet Neurol 10: 140-147.
6. Querin et al. (2013) Pilot trial of clenbuterol in spinal and bulbar muscular atrophy. Neurology 80: 2095-2098.
7. Preisler et al. Effect of aerobic training in patients with spinal and bulbar muscular atrophy (Kennedy disease). Neurology. 2009;72(4):317-23.
8. Shrader et al. (2015) A randomized controlled trial of exercise in spinal and bulbar muscular atrophy. Ann Clin Transl Neurol 2: 739-747.