As of May 2020, the KDA has awarded $1,705,339 in research grants to help find a cure or treatment for Kennedy's Disease. The 2020 recipients are listed below. To see all of the research grants funded, click here.
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.
"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
In 2020, four research grants were awarded totaling $196,200. Award recipients are listed below as well as a link to previous years grant recipients.
Characterizing the high prevalence and founder effects for Kennedy’s disease in Indigenous peoples of western Canada.
Dr. Gerry Pfeffer (University of Calgary)
In this project, we will learn about the prevalence and genetic findings of patients with Kennedy's disease who are of Indigenous descent in western Canada. We have a community engagement plan that will include patients as partners in this research. Participants will be recruited using clinic databases, research assistant contact in our clinics, and contact with family members of recruited participants. We will collect clinical data and family history information. We will also collect DNA samples to identify founder haplotypes. Once we have estimates for the prevalence and genetic origins of Kennedy's disease in these communities, we will communicate results back to participants and communities. This will lead to future study and one of our main goals is to ensure that these communities are receiving the resources they need to support people affected by Kennedy's disease.
Targeting the interaction of poly-Q expanded AR receptor with pVHL to ameliorate SBMA
Antonella Falconieri, PhD (University of Padova)
Spinal and Bulbar Muscular Atrophy (SBMA) is a neuromuscular disease caused by poly-glutamine (poly-Q) expansions in the androgen receptor (AR), which result, upon ligand binding, in misfolding, aggregation and accumulation. A factor contributing to AR aggregation in SBMA cells is inefficient degradation. AR has been shown to interact with the von Hippel-Lindau protein (pVHL), an E3 ubiquitin ligase that I found to associate with MDM2, protein involved in AR degradation. Here, I propose to elucidate the molecular details of AR/pVHL association and investigate its biological effects to demonstrate the role of pVHL in AR degradation. I will also test PROTAC molecules, already used to induce AR degradation in prostate cancer through pVHL, to study their efficacy in pVHL/MDM2-mediated polyQ-AR degradation in SBMA cells. These experiments may ultimately lead to development of a novel therapeutic strategy for SBMA treatment.
A drug repurposing strategy to inhibit AR transcriptional coactivators as a therapeutic approach in SBMA
Manuela Basso, PhD (University of Trento)
Kennedy’s disease is a neuromuscular condition caused by a mutation in the androgen receptor (AR). AR is a transcription factor, which means that it controls what the cells need to transcribe or not to stay healthy. It does that by interacting with other proteins called transcriptional coactivators. The mutation leads to a protein with altered functions; some are lost, others are enhanced. We have collected interesting evidence that by modulating the interaction with two specific AR partners that are increased during the disease, we can reduce the aberrant AR activity and preserve its normal function. We propose to investigate how the enhancement of these two factors contributes to motor neuron and muscle pathology. At the same time, we propose to use safe and well-tolerated drugs that inhibit these two factors to test whether this could be a successful therapeutic approach for the patients.
Unveiling regenerative and metabolic features of SBMA muscle cells to identify new therapeutic targets.
Mariarita Galbiatti, PhD (University of Milan)
Skeletal muscle cells have a primary role in the SBMA pathogenesis. The aim of this project is to clarify how the elongated androgen receptor induces muscle fiber dysfunctions. To achieve this goal, we will take advantage of induced pluripotent stem cells differentiated to skeletal muscle cells, and of skeletal muscle of an SBMA mouse model at different disease stages. We will focus on two different processes: the metabolism and the regenerative ability of SBMA affected muscle cells. Explaining the mechanisms of toxicity of the elongated androgen receptor in muscle will permit us to target therapeutics to key pathological stages, and to identify useful biomarkers for disease diagnosis and the reading of clinical trial results.