New Research Reported on Kennedy’s Disease

Dr. J. Paul Taylor of St. Jude Children’s Research Hospital and seven other researchers published a new research report this week.  Dr. Taylor is also a member of the Kennedy’s Disease Association Scientific Review Board as well as a longtime supporter of the KDA.  Note:  I am including the full links today in case your browser does not allow for redirection links. 

The press release can be found on EurekAlert (http://www.eurekalert.org/pub_releases/2010-09/sjcr-sln092210.php).  The entire article can be read and downloaded from Neuron (http://www.cell.com/neuron/abstract/S0896-6273%2810%2900677-X?script=true).  

I am awaiting on a response from our biology professor of what the research means for those of us living with Kennedy’s Disease, but the press release does a nice job of explaining the seventeen-page report.  I have included some excerpts from the press release below.

"The idea that toxicity is mediated by the native, or normal, function of the protein itself is a departure from conventional wisdom. This research adds to growing evidence the principle applies very broadly in other neurodegenerative disorders, including Alzheimer's and Parkinson's diseases," said J. Paul Taylor, M.D., Ph.D., an associate member in the St. Jude Department of Developmental Neurobiology and the paper's senior author.

Taylor said: "Our findings suggest the focus on protein aggregation inside cells may be misplaced." Developing therapies that target the normal protein function will likely be easier and more effective, he added.  Medications are already available to block the androgen receptor (AR) protein, which is mutated in SBMA. Work is now underway in Taylor's laboratory to identify drugs that more selectively block AR functioning.

After earlier work by other investigators showed that blocking testosterone prevented male mice with the SBMA mutation from developing the disease, Taylor and his colleagues set out to track what happened inside cells after the hormone bound to the mutated AR protein.

Working in a Drosophila fruit fly model of the disease, the scientists identified a small region of the AR protein, known as the AF-2 domain, which played a pivotal role.  Using a variety of techniques, researchers demonstrated they could rescue the cells by preventing certain members of a family of proteins called coregulators from binding to the AF-2 domain. Coregulators partner with AR and other transcription factors to regulate gene expression. 

"In this study, we showed the ability of the mutant protein to interact with the normal binding partners is an essential step in the cascade of degeneration. By blocking it, we block degeneration," Taylor said.

And, drum roll please ...

“The findings also hold hope that treating or preventing SBMA by selectively disrupting AF-2 binding will soon be possible,” Taylor said. "Selectively blocking the hormone will be key if we hope to prevent the side effects associated with androgen ablation in males," he said.  The study also suggests the need to begin treatment earlier. If the damage to motor neurons begins with the hormone surge of puberty rather than the accumulation of mis-folded proteins, therapies must begin in childhood, Taylor said.

 

As I learn more, I will let you know.