California scientists studying the neuromuscular disorder known as Kennedy’s disease have uncovered a new therapeutic target. Their discovery could lead to a treatment for the incurable illness.
Researchers from the University of California, San Diego School of Medicine focused on the cause of the inherited condition, previously thought to be an affliction involving primary motor neurons, according to Medical News Today. These are cells located in the brain stem and the spinal cord that govern movement of muscles.
Kennedy’s disease is also called spinal and bulbar muscular atrophy (SBMA). The findings of the California team, published in the journal Neuron, chronicle studies of mice showing that mutant protein levels in muscle cells rather than motor neurons are involved in SBMA.
The National Organization for Rare Disorders, Inc. says that the progressive condition usually strikes only males and typically appears in patients between 20 and 50. The disorder affects fewer than 1 in 150,000 men. While life expectancy is usually normal, a small number of patients die in their 60s or 70s.
Among early symptoms of Kennedy’s disease are hand tremors, muscle cramps after exertion, and muscle twitches under the skin, according to the National Institute of Neurological Disorders and Stroke. More advanced signs include limb weakness and facial and tongue muscle weakness, which can lead to difficulties with swallowing and speech. Some patients develop recurrent aspiration pneumonia, non-insulin-dependent diabetes, a low sperm count, and/or enlargement of male breasts.
The illness has no known cure. Treatment is supportive and typically includes physical and rehabilitation therapy to slow muscle atrophy or weakness.
Kennedy’s is an X-linked recessive disease, which means females carrying the defective gene have an even chance of passing it to a son. As is the case with Huntington’s disease, a specific DNA sequence repeats too often. This results in the development of a protein with excessive glutamines, a process that causes the diseased protein to misfold. Clinical trials with humans to guard against the repeated toxicities that occur have so far failed.
The San Diego team first created a new mouse model for SBMA, then found that mutant protein toxicity occurred in skeletal muscle. They discovered that measures that lessened the influence of the protein in muscle were able to suppress SBMA symptoms like weight loss and progressing weakness in treated mice and increased survival.
In a second paper, published in Cell Reports, the researchers described a potential SBMA treatment. They developed sequences of synthesized genetic material known as antisense oligonucleotides. These substances suppressed the expression of a particular gene in peripheral tissues, but not in the central nervous system.
The scientists indicated that antisense therapy helped SBMA mice regain muscle weight and strength and live longer. Their current goal is to refine what they have learned from their work with mice and test their methodology in human beings.
Vonda J. Sines has published thousands of print and online health and medical articles. She specializes in diseases and other conditions that affect the quality of life.