Sometimes known as Kennedy’s disease, spinal and bulbar muscular atrophy (SBMA) is a rare inherited neuromuscular disorder characterized by slowly progressive muscle weakness and atrophy. Researchers have long considered it to be essentially an affliction of primary motor neurons – the cells in the spinal cord and brainstem that control muscle movement.
But in a new study published in the April 16, 2014 online issue of Neuron, a team of scientists at the University of California, San Diego School of Medicine say novel mouse studies indicate that mutant protein levels in muscle cells, not motor neurons, are fundamentally involved in SBMA, suggesting an alternative and promising new avenue of treatment for a condition that is currently incurable.
SBMA is an X-linked recessive disease that affects only males, though females carrying the defective gene have a 50:50 chance of passing it along to a son. It belongs to a group of diseases, such as Huntington’s disease, in which a C-A-G DNA sequence is repeated too many times, resulting in a protein with too many glutamines (an amino acid), causing the diseased protein to misfold and produce harmful consequences for affected cells. Thus far, human clinical trials of treatments to protect against these repeat toxicities have failed.
In the new paper, a team led by principal investigator Albert La Spada, MD, PhD, professor of pediatrics, cellular and molecular medicine, and neurosciences, and the associate director of the Institute for Genomic Medicine at UC San Diego, propose a different therapeutic target. After creating a new mouse model of SBMA, they discovered that skeletal muscle was the site of mutant protein toxicity and that measures which mitigated the protein’s influence in muscle suppressed symptoms of SBMA in treated mice, such as weight loss and progressive weakness, and increased survival.
In a related paper, published in the April 16, 2014 online issue of Cell Reports, La Spada and colleagues describe a potential treatment for SBMA. Currently, there is none.
The scientists developed antisense oligonucleotides – sequences of synthesized genetic material – that suppressed androgen receptor (AR) gene expression in peripheral tissues, but not in the central nervous system. Mutations in the AR gene are the cause of SBMA, a discovery that La Spada made more than 20 years ago while a MD-PhD student.
La Spada said that antisense therapy helped mice modeling SBMA to recover lost muscle weight and strength and extended survival.
“The main points of these papers is that we have identified both a genetic cure and a drug cure for SBMA – at least in mice. The goal now is to further develop and refine these ideas so that we can ultimately test them in people,” La Spada said.
"Recorded on April 15th, this total lunar eclipse sequence looks south down icy Waterton Lake from the Waterton Lakes National Park in Alberta, Canada, planet Earth. The most distant horizon includes peaks in Glacier National Park, USA. An exposure every 10 minutes captured the Moon’s position and eclipse phase, as it arced, left to right, above the rugged skyline and Waterton town lights. In fact, the sequence effectively measures the roughly 80 minute duration of the total phase of the eclipse. Around 270 BC, the Greek astronomer Aristarchus also measured the duration of lunar eclipses - though probably without the benefit of digital clocks and cameras. Still, using geometry, he devised a simple and impressively accurate way to calculate the Moon’s distance, in terms of the radius of planet Earth, from the eclipse duration. This modern eclipse sequence also tracks the successive positions of Mars, above and right of the Moon, bright star Spica next to the reddened lunar disk, and Saturn to the left and below." (NASA)
One is the remnants of our solar system’s birth, and the other holds the seeds for solar systems dead and yet to come. Some more dusty goodness to go along with this week’s dusty episode of IOTBS on YouTube.
Photo by the superbly talented Cory Schmitz (Flickr, used with permission)
A mushroom cloud rises 65,000 feet over a devastated Nagasaki, Japan on August 9, 1945, killing over 70,000 people with thousands more left to die in the radioactive fallout. The Second World War would end a few days later when the Empire of Japan tentatively surrendered to Allied forces.