Mutant Protein in Muscle Linked to Neuromuscular Disorder
A new therapeutic target for Kennedy’s disease and a potential treatment
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.
Pictured: striated human skeletal muscle.
FLUORITE (Calcium Fluorite) crystals from Cave-In-Rock, Illinois, USA.
In Greek mythology, the Erinyes were female chthonic deities of vengeance; they were sometimes referred to as “infernal goddesses”.
two lionesses and their cubs taking an early morning stroll in kenya’s masai mara. photos by david lazar
Crow tried to steal our songs for himself, so I don’t know about you but he isn’t revered and sacred and definitely isn’t honored in my North America Mythos. Differing cultural stories don’t really have much of a place here.
State of Idaho plans to poison up to 4,000 Common Ravens.
Justification: Ravens prey on the eggs of the imperiled Greater Sage-Grouse. Yet of 19 reasons for the grouse’s declining numbers, predation by other wildlife comes in at #12. Providing protected areas and requiring sustainable land management are the most important ways to conserve the grouse, not killing avian predators.
(via: American Bird Conservancy)
It’s really close, please sign guys!
killing one species to ‘protect’ another is a horrible approach to anything. Have people not learned by now? And how many other animals would this inevitably poison? Ones that would also not only ingest the poison, but the poisoned bird carcasses.
What is wrong with people.
Crows and Ravens hold a sacred position in the Mythos of North America, they should be honored and revered not murdered.
If you thought the post on twins sharing consciousness was awesome, wait until you hear this.
A 44-year-old French man one day went to the trip to the doctor’s because he felt a pain in his left leg. He’s a married man with two kids and a steady job.
Doctor’s found that he had hydrocephalus as a child (when your brain is filled with fluids) so they decided to run some brain scans.
What they found was that the majority of his head was filled with fluid. Over time, the buildup caused his lateral ventricles to swell so much that his brain had been flattened to a thin sheet.
Doctors estimated that his brain mass had been reduced by at most 70%, affecting the areas in charge of motion, language, emotion, and, well, everything.
Shockingly, he was fine. While his IQ was only 75, he wasn’t mentally challenged. He held a steady job, raised a family, and didn’t have trouble interacting with others.
Over time, his brain had adapted to all that pressure, and even though he had fewer neurons that most, Jacques was still a fully functional human being.
The doctors drained the fluid and while his brain is much smaller now, he is still a healthy individual with a normal life.
Blood Moon gif stabilized and slowed.
Common names: Javan Chevrotain, Kanchil, Javan Mousedeer, Java Mousedeer, Lesser Mouse Deer, Lesser Malay Mouse Deer, Pilandok, Ciervo Ratón de Java.
Tragulus javanicus (Artiodactyla - Tragulidae) is a small antlerless ungulate, considered the smallest artiodactyl, 18-22 inches long with a tail length of 2 inches.
Adult males have elongated, tusk-like upper canines. These canines protrude from the side of the mouth. Females lack these canines and are also smaller than the males. Mouse deer have no upper incisors, they have triangular head, and a round body with elevated rear quarters. The thin legs are about the diameter of a pencil .
Tragulus javanicus is endemic to the island of Java, Indonesia