The Clinical Features of Kennedy’s Disease

In October of last year, a paper was published on the findings of 57 patients with Kennedy's Disease here in the United States. It is somewhat different in scope than the "Natural History of SBMA" report I discussed in May. The information provided in this report was obtained during the last NIH clinical trial. The title of this report is "Clinical Features of Spinal and Bulbar Muscular Atrophy." In today's article I will highlight certain findings that I found interesting. I would recommend that if you are interested, please follow the link above and read the entire paper.

This report also concluded that the longer the CAG repeat length (number), the earlier the onset. It also commented that the longer the CAG repeat length, the greater the abnormalities in motor and sensory nerve conduction. 94-to-100% of the patients had some sensory problems. They reported that there was a significant difference in the MUNE (motor unit number estimation) between SBMA subjects and the control (healthy) group. This sensory nerve issue (nerve conduction) has been one that has bothered many of us with Kennedy's Disease for some time. The tingling or numbness in the feet, hands or other parts of the body has been frustrating, because it had not been reported as a symptom until recently. (Table 5 reviewed the results of this study)

It also explained that the androgen receptor is a nuclear receptor that normally regulates gene expression and ligand binding (normally testosterone and dihydrotestosterone). Recent studies indicate that these bindings are important in the development of Kennedy's Disease. It concluded that Kennedy's Disease manifestations are primarily due to a ligand-dependent toxic gain of function in the mutant androgen receptor (whew ... what a mouthful). They gave several examples of observations that promote this hypothesis.

The most affected ADL (activities of daily living) were walking, falling, swallowing, speech, and handwriting. Only nine patients reported no difficulty with falling (oh, to be so lucky).

The report had several charts and graphs amplifying the clinical findings and I encourage you to review them. I will emphasize some of the interesting information below.

• The average age of the first muscle weakness was 41 (range of 18-to-64).
  
• The mean average from time of noticing muscle weakness to clinical diagnosis was 5½ years.
  
• The average age of diagnosis was 47 years.
  
• 32% of the patients reported being misdiagnosed initially.
  
• The average CAG repeat length was 46.7 (range of 41-to-53).
  
• The most common initial symptom was muscle cramps followed by tremors and leg weakness.
  
• Half of the patients reported initial weakness in the legs while another third reported bulbar symptoms.
  
• 68% of the patients knew of other family members with Kennedy's Disease.
  
• 88% of the patients had elevated Creatine kinase.
  
• The strength in 11 muscle groups ranged from 38-to-70% of the healthy control group. (Table 4 was interesting to me)
  
• The weakness was asymmetric in 62% of the patients with 69% having more weakness in the dominant side.
  
• 22 of the 56 patients used assistive devices such as canes, walkers, or ankle-foot orthoses.
  

One of the most interesting conclusions was ... "In development of a treatment for SBMA, early intervention may also be important to affect disease progression." We, old codgers, lose out again.

Another finding was interesting ... "Our finding that higher, not lower, testosterone levels are associated with better muscle strength and function indicates that it may be necessary to balance the anabolic strengthening effects of androgen receptors against any potential deleterious effects (harmful, often in an unexpected way) of androgen-activated mutant androgen receptor toxicity (another whew)." I need to determine what this actually means. We know that testosterone is like poison to our defective (mutant) androgen receptor. We also know that the Ohio State trial of testosterone injections in the late 90s did not work. Yet, this study reflects that patients with higher testosterone levels had better muscle strength (and that makes sense) ... except that the higher the testosterone the greater damage to the muscles and motor neurons because the androgen receptor cannot do its day job. Nothing is every easy.

Well, I hope you find this report as interesting as I did. Let me know your thoughts and conclusions if you have a chance.