Click here to view a list of KDA funded grants.  If you are a Research Lab you will find information on our grant application process and required forms here also.

Current Research

Below you will find current information on Kennedy's Disease research

January 17, 2008

Two grants just funded by the KDA both attempt to investigate mechanisms to prevent the accumulation of the toxic fragment in cells containing the mutant AR.

Briefly, KD is caused by a genetic mutation to the gene that codes for the Androgen Receptor (AR) protein.  This protein mediates all the actions of the androgen hormones testosterone and dihydrotestosterone, DHT.  In the cells of normal males, the AR is found in the cytoplasm of the cell.  Upon the addition of an androgen hormone (either testosterone or DHT), the hormone binds to the AR and the hormone/AR complex travels to the nucleus of the cell where it initiates the masculine changes that are associated with the presence of androgens (beard growth, for example).  If there is no androgen present, then the AR never enters the nucleus and there are no changes – this is essentially what occurs in females.  Since women do not possess androgens, the AR does nothing in cells and there are no masculine effects.  The AR in the nucleus is ultimately destroyed by a cell structure known as the proteasome.  In individuals with KD, the cell is unable to completely destroy the AR that enters the nucleus - but it can destroy the AR that does not enter the nucleus and this inadequate digestion apparently results in the production of a fragment of the mutant AR that is toxic to the cells – thus the cells die and this leads to the formation of the symptoms of KD.  This appears to explain why women carriers do not show major symptoms.  Since the levels of androgens in women are low, the mutant AR does not enter the nucleus and the cell does not create the toxic fragment.

A $25,000 grant was awarded to Maria Pennuto, Ph.D. from the National Institute of Health.  Dr. Pennuto has spent the past few years investigating the molecular switches on the AR that are involved in the movement of the AR into the nucleus upon addition of hormone.  She has discovered that certain chemical changes to the AR seem to reduce the ability of the AR to bind to hormone and thus not enter the nucleus (and cause KD!!).  She has discovered that the exposure of cells to a substance known as IGF-1 can induce these chemical changes to occur to the mutant AR and thus prevent the movement of the AR to the nucleus.  Thus, the addition of IGF-1 to a cell with mutant AR appears to prevent the formation of the toxic fragment and thus the cell stays alive.  Dr. Pennuto will continue this work by determining if any other chemical changes to the AR may alter its movement to the nucleus and  she will also determine if IGF-1 prevents the formation of KD symptoms in a KD mice model (up to this time, the effect of IGF-1 has only been shown to work in cell cultures.  This work could lead to new therapies for KD.

Another $25,000 grant was awarded to Udai Bhan Pandey, Ph.D. from the University of Pennsylvania.  The proposal by Dr. Pandey and Dr. Paul Taylor continues the work that they did (in part thanks to a previous KDA grant!).  They previously reported that KD symptoms in a fly model of KD could be reduced by activating another mechanism for destroying the KD in the nucleus, by passing the need for the proteasome.  This alternate pathway, known as autophagy, apparently is capable of destroying the toxic fragment.  They did this by making the fly over produce another protein known as HDAC6.  By doing this, they were able to demonstrate that the overproduction of HDAC6 did not show cell death despite the presence of the mutant KD.  They will now try to continue this work as they attempt to find other proteins that may affect this activity of HDAC6 to stimulate autophagy and thus help prevent the cell death associated with KD.

Other awardees in previous years include:

• J. Paul Taylor (twice), MD, PhD, Department of Neurology, University of Pennsylvania
• Andrew Lieberman, MD, Department of Pathology, University of Michigan
• Chawnshang Chang, Ph.D. from the University of Rochester
• Udai Bhan Pandey, Ph.D. from the University of Pennsylvania

Each received grants of $25,000.  Their work has been reported on regularly and is aiding in the attempt to find a treatment or cure for Kennedy's Disease.  The KDA also thanks all the researchers who have dedicated themselves to this cause as well as our Associates, businesses, and friends who continue to support the funding of these grants.
 

March 27, 2007

Two interesting papers, well, interesting to those with KD, were published during the past several weeks.  Read more here

The first paper is Soluble Androgen Receptor Oligomers Underlie Pathology in a Mouse Model of Spinobulbar Muscular Atrophy.by Li, Chevalier-Larsen, Merry and Diamond. 

March 20, 2007

March 2, 2007 - 2 Articles

SBMA Mice Answer some questions, Raise others.

Please follow the link to the article.  Note: This research article speaks of Andrew Lieberman's lab research. Andrew Lieberman is on the Kennedy's Disease Association's Scientific Review Board..  Click here to go to the article.

Androgen Receptor's, Protein Blocking Explored in SBMA (Kennedy's Disease) Note: This research article speaks of Albert La Spada's lab research. Albert La Spada is also on the Kennedy's Disease Association's Scientific Review Board.  Click here to read the article.

Sept 16,2006

Muscle pathology in mice with Kennedy's Disease 

Announcing the results of a University of Michigan research study that is related to Kennedy's Disease.  The research project was partially funded by the KDA through the generous donations of our associates, their family, and friends.

Click here to read the report 

July 31, 2005 In Year 2002, the KDA sent a questionnaire to all current KDA Associates.  There were hundreds of questions to try to get a snapshot of KD symptoms, lifestyles, etc.  34 responded and the results have been painstakingly tallied.  Click Here to see the compiled reports.

June 2004 KDA funded research grant update - The KDA funded a grant to J. Paul Taylor, MD PhD at University of Pennsylvania for $25,000 in November 2003 for a Drosophila melanogaster (fruitfly) model system to investigate the molecular pathogenesis of Spinal and Bulbar Muscular Atrophy.  Dr. Taylor has provided us with an update as to how their research is coming along. Please Click Here to read the update.

KDA awards Andrew Lieberman, PhD at University of Michigan a research grant in the amount of $25,000 in January 2004

KDA awards J. Paul Taylor, MD, PhD at University of Pennsylvania a research grant in the amount of $25,000 in November 2003

April 2003 - Possible drug treatment for Kennedy's may be on the horizon Scientists Search for Drugs to help Kennedy's Disease At the 55th Annual meeting of the American Academy of Neurology, scientists reported  that they've scored multiple "hits" in a screen for drugs that might be useful against Kennedy's disease.

Recent Studies Indicate Testosterone may Aggrevate Kennedy's Disease (September 2002)

Studies indicate that ligand, i.e. testosterone, is responsible for setting in action the toxic effects of the expanded repeat androgen receptor in KD mouse models.  This is an important finding that indicates that testosterone may NOT be a good therapy for KD. A reduction of testosterone in this mouse model of Dr. Sobue's reduced the toxic effects of the mutant androgen receptor.

 However, the use of antagonists (drugs that counter the effect of testosterone) to the androgen receptor are not warranted either, as the accompanying paper on a fly model of SBMA shows that the use of antagonists that promote the transfer of the receptor into the nucleus of the cell (which testosterone does), also promotes disease symptoms. Please see the links to the files below.  They are fairly large files and may take a few minutes to download depending on your connection speed so please be patient.

The below files are Adobe Acrobat files.  You will need to download Adobe Acrobat viewer if have not already done so.  Go to www.adobe.com to get the viewer - click on the "Download Acrobat Reader" under the "Support" section.

File 1            File 2          File 3