KDA Research Grant(s) will be available again this year. Please see the 2009 Letter of Intent for more detailed information. Also see below details of for a full grant proposal.

Concept:  Because the KDA is relatively small and funding is limited, our focus in recent years has been to provide “seed-money” to post-doc and other young researchers who do not currently have the funding or credentials to receive funding from larger organizations such as the National Institute of Health or the MDA.  This “seed-money” normally provides the researcher an opportunity to further his/her research while giving him/her time to apply for other grants

Process:  In recent years, the awarding process takes place in the fall.  In the late summer, the KDA announces to all known Kennedy’s Disease Researchers that anyone interested should send in their grant requests by late August.  The Scientific Review Board reviews all applications.  The reviewers focus on research projects that are specific to or could be used in finding a treatment or cure for Kennedy’s Disease.  The reviewers ask three or four of the applicants to submit full grant applications by the end of September.  In late October, the Scientific Review Board reviews the finalists and recommends to the Board of Directors which applicant(s) should receive research funding.  By late November, the Board of Directors awards the grants.

Full Grant Proposal Template
 

KDA RESEARCH GRANT AWARDS:   As of Dec 31, 2009 the KDA has given $ 280,000 in research grants to help find a cure or treatment for Kennedy's Disease.

Previous Award Recipients:

2009 -  3 research grants were funded:

#1. $25,000 Parsa Kazemi-Esfarjani, B.Sc., Ph.D. is a researcher for the Department of Pediatrics, Division of Genetics, Institute for Genomic Medicine at the School of Medicine, University of California, San Diego 

Essentially this research will attempt to determine whether or not, and to what extent, the mutant androgen receptor (AR) in the muscle contributes to both muscle atrophy and motor neuron degeneration in Kennedy’s Disease (KD).  They have produced a mouse model of KD in which they can remove the mutant AR gene just in the muscle cells (this is due to a genetic manipulation), leaving the mutant AR intact in the rest of the cells.  This type of research will hopefully show us which cells and tissues are the most important for the timing of the appearance of KD symptoms (i.e., the onset) and/or the pace of their progression. With this knowledge, we will be able to develop our therapies for KD more effectively and target them to the appropriate tissues.

 

#2  $20,000  Maria Pennuto,Ph.D. Department of Neuroscience, Italian Institute of Technology, Genova, Italy.

This research is based on results that Maria found when she worked in Dr. Fischbeck's lab at NIH.  She had found that a specific modification of the mutant androgen receptors (AR) results in decreased toxicity and that this modification was due to the activation of an enzyme known as PKA.  She intends to investigate more thoroughly the relationship between PKA and toxicity and to search for drugs that may activate PKA and thus may lessen the effects of the mutant AR.

 

#3 $10,000 Lenore Beitel, Ph.D. Lady Davis Institute for Medical Research, SMBD-Jewish General Hospital, Montreal, Quebec, Canada  

This research is to further study the role of the proteasome and its ability (or lack of ability) to degrade mutant androgen receptors (AR).  She hopes to determine directly if the mutant AR really does 'clog' up the proteasome.  Up to this point, most of the evidence for such an effect is circumstantial.

2008 -  One $ 50,000 research grants were funded:

At the Kennedy's Disease Association's Annual Conference and Research Symposium in November, Board Member Ed Meyertholen awarded Heather Montie, Ph.D., with a $50,000 check to support her Kennedy's Disease research at Thomas Jefferson University in Philadelphia.  This grant will fund research that will investigate the androgen receptor (AR) - this is the protein that is altered in Kennedy's Disease (KD).  The AR mediates all the effects of testosterone in cells.  Without the AR, testosterone will have no effect. Normally, the AR is activated by testosterone.  Once activated by testosterone, the AR causes changes in the activity of the cell.  It is believed that in cells from those with KD, the cell is not capable of removing the 'old' AR that has been used and this somehow results in the death of the cells.  Preliminary research by Dr. Montie and her colleagues have indicated that the KD form of AR is chemically altered by the cell through a process of hyperacetylation and it is possible that if this process is blocked, the cell may be more capable of removing the AR and thus should not die.  The KDA grant will allow Dr. Montie continue her studies on the role of acetylation of AR  and to determine if blocking this process does reduce the death of cells with mutant KD

2007 -  Two $ 25,000 research grants were funded: 

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.

2006, Two $ 25,000 research grants were funded: 

A $25,000 grant was awarded to Chawnshang Chang Ph.D. from the University of Rochester.  His research plans to develop a treatment regimen for Kennedy’s Disease targeting the poly Q-expanded mutant AR.  This concept may be a way to cure the disease.

Another $25,000 grant was awarded to Udai Bhan Pandey Ph.D. from the University of Pennsylvania.  Dr. Pandey proposes to use molecular genetic approaches in Drosophila to characterize the mechanism of suppression by HDAC6.  His long-term goal is to contribute to the development of therapeutic interventions for Kennedy’s Disease.

2005, one $ 25,000 research grant was funded:

A $25,000 emergency funding grant was awarded to J. Paul Taylor, MD, Ph.D. from the University of Pennsylvania.  The grant helped support Dr. Taylor and his team's research using the Drosophila melanogaster (fruitfly) model system to investigate the molecular pathogenesis of Spinal and Bulbar Muscular Atrophy (aka Kennedy's Disease).  In response to the KDA's grant, we received the following email from Dr. Taylor referencing the status of his current Kennedy's Disease research.  "... This (grant) could be a life saver.  We have made great strides with our work, in fact, we have a manuscript on our Kennedy's Disease work that has received good reviews.  This work was largely funded by (the) KDA and I have been anxiously waiting for this work to be accepted for publication before alerting you.  I have also had two graduate students join my lab who are doing their Ph.D. thesis work on Kennedy's Disease.

2004, One $ 25,000 research grant was funded: 

A $25,000 grant was awarded to Andrew Lieberman, MD, Ph.D., University of Michigan for development of First Ever Kennedy's Disease Knock-In Mouse Model.  "Thanks so much for all of your hard work on our behalf!  It sure is inspirational for us to know that the KDA cares enough about this project to launch a difficult fund raising drive to support our work, and it's really gratifying to see that the generosity of the KDA membership made these efforts successful so quickly."  --  Dr. Andrew Lieberman

2003, one $ 25,000 research grant was funded: 

A $25,000 grant was awarded to J. Paul Taylor, MD, PhD, University of Pennsylvania for developing the Drosophila melanogaster (fruitfly) model system to investigate the molecular pathogenesis of Spinal and Bulbar Muscular Atrophy.