2016 Research Grant Award Recipients and Information
As of November, 2016, the KDA has awarded $834,214 in research grants to help find a cure or treatment for Kennedy's Disease. The below 2016 research grant award recipients have been awarded $50,000 each
Dr Bilal Malik
Professor Linda Greensmith’s Lab, UCL, Institute of Neurology, UK
Targeting pathways of disease in Spinal Bulbar and Muscular Atrophy (SBMA)
Spinal and Bulbar Muscular Atrophy (SBMA), also known as Kennedy’s disease (KD), is adult-onset slowly progressing rare inherited neuromuscular disorder that primarily affects males. As yet there are no effective treatments that can cure the disease or delay its progression. The disease is primarily characterised by muscle weakness and wasting, and degeneration of motor neuron cells within the spinal cord and brain.
Our aim is to establish why motor neurons and muscles degenerate in SBMA by investigating the genes and pathways that underlie disease. The identification of changes that occur early in disease may identify the mechanisms responsible for disease and help establish novel therapeutic targets. This proposal offers the unique opportunity to undertake a comparative study of two platforms that model SBMA, each with its own merits: i) a well-characterised mouse model in which muscle and motor neurons can be examined at various stages of disease, and ii) human cell models, including stem-cell derived motor neurons and patient muscle cells acquired from biopsies. By comparing and contrasting the changes in gene expression in these models of the specific cells affected in SBMA we hope to identify the key changes in gene expression that take place early in disease, identifying a common signature in the pathways of pathology. The results of this study will not only help define novel therapeutic targets with a greater level of confidence by analysing several complimentary models of SBMA, but also allow us to test treatment strategies in a human cell model of the disease.
Dr. Janghoo Lim
Yale University School of Medicine
The role of VCP in the pathogenesis of Kennedy's disease
Spinal and Bulbar Muscular Atrophy (SBMA; Kennedy’s Disease) is a neuromuscular disease
that affects motor neurons and skeletal muscles. The symptoms of SBMA include progressive
weakness of the limbs and facial muscles, as well as difficulty with speaking and swallowing.
SBMA is an X-linked disease that primarily affects men, and is caused by a polyglutamine
expansion in the gene Androgen Receptor (AR). The polyglutamine expansion in AR makes the
protein toxic, and can lead to the formation of protein aggregates inside of cells as well as cell
death. SBMA is one of nine different polyglutamine expansion disorders that are linked to
neurodegeneration. How polyglutamine expanded AR causes SBMA is still being studied, and
there are no effective therapeutics available. In order to better understand the mechanisms that
cause SBMA and translate these results into the development of effective therapeutics, my
proposal aims to assess how the protein Valosin-Containing Protein (VCP) is involved in SBMA.
VCP plays a role in breaking down mutant or damaged proteins, and has been studied in other
neurodegenerative disorders. Based on our preliminary data, we hypothesize that VCP can
regulate the expression and/or the activity of polyglutamine expanded AR. Our proposal will
examine how VCP affects the development of protein aggregates and cell death in SBMA. We
will use cell culture models and fruit flies, both of which are commonly used to study SBMA.
This research will help develop a more thorough understanding of what causes SBMA, and
provide important information when developing new therapeutics for this devastating disease.
Manuela Basso, Ph.D.
Laboratory of Transcriptional Neurobiology
Centre for Integrative Biology
University of Trento
Insights into the molecular pathology of SBMA: Targeting PRMT6 to attenuate the disease.
In collaboration with the Laboratory of Dr. Pennuto, we have recently discovered that a protein, called PRMT6, exacerbates the toxicity induced by mutant androgen receptor, while its inhibition rescues it in cells and flies. Our strategy is to develop a therapy that preserves AR physiological functions while abolishing the toxicity acquired upon polyglutamine expansion. Thus, we propose to silence PRMT6 both via selective pharmacological inhibitors and via gene-silencing to choose the best system to move our studies in pre-clinical models.
"I received a pilot grant from the KDA early in my career at a particularly vulnerable time for young scientists, before receiving my first grant from the NIH. The foundation's support made a big impact, helping enable us to generate a mouse model that we continue to study to understand disease mechanisms and therapeutic targets."
Andrew Lieberman, MD PhD
University of Michigan Medical School
Every summer the KDA accepts research grant proposals. Grants are awarded in the late fall of each year.
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
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 as outlined in the proposal notification. The Scientific Review Board reviews all applications with a focus on research projects that are specific to or could be used in finding a treatment or cure for Kennedy’s Disease. The Scientific Review Board recommends to the Board of Directors which applicant(s) should receive research funding. The Board of Directors notifies all candidates and awards the grants normally in October.