Research Grants

KDA Awards $530,500.00 In Research Grants in 2024

As of November 2024, the KDA has awarded $2,784,117.00 in research grants to help find a cure or treatment for Kennedy's Disease. Please scroll down to see the past grant award recipients. 

Grant Award Information

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Grant Award Recipients

Fall 2024 Grant Award Recipients

The KDA awards 2024 research grants totaling $330,500.00. Research grants awarded with a lay summaries below.   

• Mary McMahon, Phd. Director of Biology at Therapeutics (ReviR), Reward amount $99,500.
• Nathan Beckouche, Phd. Atmos R - Institute of Psychiatry and Neurosciences of Paris, Reward amount $100,000.
• Gianni Soraru, Md. Phd. MND Center, Department of Neurosciences - University Hospital of Padua, Italy, Reward amount $54,000.
• Annalucia Darbey, Phd, University College London  Reward amount $75,000 plus $2,000 travel and education expenses for the 2024 Waite-Griffin SBMA Fellowship.

Mary McMahon, PhD - Director of Biology at ReviR Therapeutics. Reward amount $99,500.

Bio 

Dr. Mary McMahon, PhD is the Director of Biology at ReviR Therapeutics, a biotechnology company pioneering innovative small-molecule RNA modulators. These treatments are designed to target neurogenetic diseases and previously “undruggable” conditions.
After earning her PhD from University College Cork, Ireland, and completing postdoctoral research at the University of California, San Francisco, Dr. McMahon delved into the molecular mechanisms behind age-related diseases like neurodegenerative disorders. Her research centered on the role of RNA processing and protein synthesis in these conditions.
At ReviR Therapeutics, Dr. McMahon is at the forefront of developing novel therapies for repeat expansion disorders such as Kennedy’s disease and Huntington’s disease.

Summary Description 

Spinal and Bulbar Muscular Atrophy (SBMA), also known as Kennedy's disease, is a progressive neuromuscular disorder triggered by an expansion of a CAG repeat within the androgen receptor (AR) gene. ReviR Therapeutics is exploring a novel approach to regulate mutant AR and is developing small molecules to reduce its harmful effects.
Funded by the KDA, ReviR will develop and test these innovative small molecules to assess their impact on mutant AR expression in SBMA models. If successful, this project could lead to a groundbreaking therapy for individuals with SBMA.
 

Nathan Beckouche, Phd. Atmos R - Institute of Psychiatry and Neurosciences of Paris, Reward amount $100,000.

Bio
Dr. Nathan Beckouche is the Chief Scientific Officer at AtmosR, where he leads groundbreaking research in rare neurological disorders. He holds a Ph.D. in Physiology and Physiopathology from the Pierre and Marie Curie University (Paris), which he followed as a postdoctoral fellow at University Of California San Francisco, which revolved around mouse genetics and disease modeling. He began his industry career at Alexion Pharmaceuticals, focusing on rare diseases in the field of nephrology. His passion for addressing unmet medical needs has driven his transition to neurological disorders, and he started working with the french patient organization for Ondine syndrome, a rare neurodevelopmental disease. He co-founded AtmosR where he leverages his expertise to develop innovative therapies for diseases with high-unmet medical needs, with a team of passionate scientists with complementary profiles. 

Summary Description
AtmosR is a Paris-based biotech company specializing in the development of treatments for rare neurological diseases. AtmosR is developing ATS-033, a therapeutic able to destroy the pathological aggregates caused by the gene mutation responsible for Kennedy’s disease. Thanks to the support of the KDA, AtmosR will test the efficacy of its compound in a mouse model of KD, focusing on the motor symptoms of the animals, in order to assess its interest for KD patients.

Gianni Soraru, Md. Phd. - MND Center, Department of Neurosciences - University Hospital of Padua, Italy, Reward amount $54,0000.

Bio

Dr. Sorarù graduated in Medicine in 1996 and specialized in Neurology in 2000. After several years as a Clinical Staff member in a Neurology Unit, he began his academic career at the University of Padova, where he is currently an Associate Professor of Neurology. His research career began in the laboratory of Prof. Corrado Angelini, focusing on muscle involvement in motor neuron diseases. During his PhD, he investigated the mitochondrial respiratory chain in ALS, discovering a link between mitochondrial complex activities and nNOS levels. He also studied skeletal muscle in patients and carriers of Kennedy’s disease, identifying an androgen-dependent myopathy. In collaboration with Prof. Maria Pennuto, Dr. Sorarù explored the therapeutic potential of beta-2 adrenergic receptor stimulation in SBMA. Their research showed that beta-agonists improve SBMA phenotypes in both mice and patient-derived myotubes. A pilot trial with clenbuterol in 20 SBMA patients demonstrated its positive impact on disease progression, leading to an ongoing randomized clinical trial (RCT). His interest in translational medicine has also led him to research genotype-phenotype correlations in ALS and the development of novel biomarkers for both ALS and SBMA. His clinical work in motor neuron diseases has contributed to a deeper understanding of these disorders and has involved his participation in over 15 clinical trials.
 

Summary Description

Recent research suggests that SBMA may also affect the autonomic nervous system, which controls functions like heart rate, digestion, and sweating. This research aims to explore how SBMA affects autonomic functions. A team of experts will study 30 confirmed SBMA patients and 20 healthy male controls. They will perform a variety of tests to assess different autonomic functions, including heart rate responses, blood pressure, sweating, and gastrointestinal functions. These tests will help understand how SBMA impacts the body’s ability to regulate essential functions beyond muscle control.

Annalucia Darbey, Phd University College London. Reward amount $75,000 plus $2,000 travel and education expenses from the 2024 Waite-Griffin SBMA Fellowship.

Bio

Dr Annalucia Darbey joined the Fratta lab at UCL Queens Square Institute of Neurology as a Postdoctoral Research Fellow in 2021.
Her research focuses on using innovative and exciting technologies to develop tissue specific Gene Therapy solutions for Motor Neuron Diseases, particularly SBMA/Kennedy’s Disease. She has been fortunate to receive a number of awards whilst at UCL including a Cell & Gene Therapy TIN Award and an AFM Telethon award – these have been crucial for her continuing development as an ECR. Prior to her work at UCL, she completed her PhD in Tissue Repair & Gene Therapy at The University of Edinburgh before moving to Newcastle, Australia for two years to investigate Gene Therapy for endocrine disorders as a Postdoctoral Research Associate.

Summary Description

Research into potential therapeutic for Kennedy’s Disease (KD) have predominantly focused on therapeutic strategies that alter the functioning, signalling and expression of the polyglutamine-expanded androgen receptor (polyQ-AR). Previous studies have shown that when expression of the polyQ-AR is reduced, particularly in skeletal muscle, the disease phenotype is improved in animal models of disease, supporting the idea for reducing muscle AR for the treatment of KD. However, thus far, investigations of strategies to reduce or modify AR expression have only been carried out in pre-symptomatic time points in mouse models, demonstrating an effective prevention of the disease. This study will utilise our novel muscle specific AR silencing system, which we will use to assess the impact of AR reduction at later time points in KD – a crucial factor for all AR modifying therapeutics. We will also assess the effectiveness and safety of our novel approach as a potential therapeutic for KD, with the added advantage that our approach is muscle-specific.  By restricting AR suppression specifically to muscle, we hope to prevent AR-reduction induced side-effects in organs where AR signalling is crucial for normal functioning. 
These experiments will provide important proof-of-principle information as to how and when AR-silencing strategies can function as a therapeutic for KD.
 

Summer 2024 - KDA Awards Grants to Research Teams

Thanks to generous donations from our members, KDA recently awarded $100,000 grants to two teams of researchers who participated in the 2023 SBMA Research Workshop held at the Banbury Center in New York. The workshop, funded by donations to the 2023 KD Golf Scramble in Magnolia, Texas, brought together participants from 15 labs in the U.S. and three other countries to discuss collaborative approaches between SBMA researchers and experts in other diseases.  

The team of Dr. Al La Spada from the University of California, Irvine, and Mina Gouti, PhD, from the Max Delbruck Center for Molecular Medicine in Berlin will study the question of “How does skeletal muscle expression of mutant AR result in motor neuron degeneration in SBMA?” The team of Helen Miranda, PhD, and Ashleigh Schaffer, PhD, of the Department of Genome Sciences at Case Western Reserve University in Cleveland will investigate “Gene expression, regulation by AR with different CAG repeat sizes in hiPSC-derived neuromuscular junctions." Both projects will use leading-edge research techniques.

KDA congratulates these scientists for their collaborative efforts, and we look forward to the results of their research. We also look forward to this year's Banbury SBMA workshop, again funded by the KD Golf Scramble. Twenty-two participants from six countries will meet to discuss the role of the cellular protein quality control system in SBMA (Kennedy's disease).

2023 Grant & Fellowship Awards.

The KDA rewarded four research grants and one fellowship totaling $437,000. Award recipients are listed below.

• $100,000 - "Identification and characterization of kinase(s) responsible for androgen receptor phosphorylation at serine 16", Masoud Shekarabi, Thomas Jefferson University.
• $69,000 - "Connecting SBMA national registries databases: a retrospective study" Davide Pareyson, Besta Institute, Milan, Italy (two-year award) $46,000 (2023) and $23,000 (2024).
• $91,350 - "Polyglutamine expansion in aggregation AR in cells", Xavier Salvatella Giralt, IRB Barcelona, Spain (two-year award) $49,350 (2023) and $42,000 (2024).
• $100,000 - "Investigating the role of CD38 in metabolic dysregulation in Kennedy’s Disease", Heather Montie, Philadelphia College of Osteopathic Medicine
• $75,000 - "Investigating differences in polyQ-AR genomic activity leading to muscle atrophy in SBMA", Anastasia Gromova, University of California, Irvine. Recipient of the 2023 Waite-Griffin SBMA Fellowship

2023 Grant & Fellowship Summaries

2023 KDA Grant Summary

Summary - $100,000 - "Identification and characterization of kinase(s) responsible for androgen receptor phosphorylation at serine 16" Post-translational modifications of AR have been shown to play important roles in its function, stability, and toxicity of its polyQ-expanded form. It was previously shown that blocking the N/C interaction in AR protein caused the hyperphosphorylation of a serine amino acid in the N-terminal domain of AR (serine 16, S16) and mitigated polyQ-expanded AR toxicity in mouse motor neurons. Because of the significant role of S16 phosphorylation and the therapeutic potential of kinases as viable targets for drug development, we seek to identify and validate the kinase(s) responsible for S16 phosphorylation. We have employed a combination of biochemical methods and have identified several kinases, which were specifically associated with S16. Here, we propose to investigate the role of kinase(s) that directly interact with and phosphorylate serine 16 in AR and to functionally determine the consequence of this activity in polyQ-expanded AR. This work therefore will study a novel mechanism that regulates polyQ-expanded AR toxicity and will identify potential novel targets for clinical intervention in SBMA.

Bio: Masoud Shekarabi completed his PhD at the Montreal Neurological Institute at McGill University, Canada and then carried out postdoctoral training in the laboratory of Dr. Guy Rouleau at the University of Montreal, where he investigated the roles of a specific kinase, WNK1, in the pathogenesis of both inherited sensory and peripheral neuropathy (HSANII) and agenesis of the corpus callosum with peripheral neuropathy (ACCPN, Anderman syndrome). The findings fueled a new understanding of WNK1 in pain related disorders. He has also researched HIV-1-associated neurological impairments and established an impaired dephosphorylation activity that plays a role in HIV pathogenesis. He is currently a senior researcher in the laboratory of Dr. Diane Merry at Thomas Jefferson University. He is applying his diverse skill set to understand the role of AR S16 phosphorylation in polyglutamine-expanded androgen receptor toxicity in SBMA. His long-term research goals are to study the molecular pathogenesis of neurodegenerative disorders by emphasizing the underlying mechanisms and role of kinases. By 2021, there have been 76 FDA approved small molecule protein kinase inhibitors that have reached clinical use. There are over 500 kinases in the human kinome; 182 of them are “dark kinases” which were not extensively researched and thus their roles in the disease of the nervous system are elusive. 

Summary - $91,350. Polyglutamine expansion in aggregation AR in cells: The Salvatella laboratory in IRB Barcelona has recently shown that the androgen receptor works by forming nuclear clusters called transcriptional condensates. AR condensation can be beneficial because it facilitates gene expression; however, it can also accelerate protein aggregation, a process in which protein molecules lose their activity by forming insoluble clumps that are harmful to cells. With the support of the KDA the team will investigate whether the polyglutamine expansion associated with Kennedy’s disease causes transcriptional condensates to become dysfunctional due to androgen receptor aggregation. In addition, it will test whether drug-like molecules can accumulate in the transcriptional condensates formed by the mutated receptor and prevent its aggregation. The work will increase our understanding of the molecular basis of the disease and allow us to explore a new therapeutic avenue for Kennedy’s disease.

Bio: Xavier Salvatella studied chemistry at the University of Barcelona (BSc) and Queen Mary College, London (MSc). He completed his PhD at the University of Barcelona, where he studied the interaction between synthetic molecules and hydrophilic surfaces in proteins such as the tumour suppressor P53. He conducted postdoctoral work at the University of Cambridge, combining experiments and simulations to investigate the structural heterogeneity of intrinsically disordered, partially folded and globular proteins. He leads the laboratory of molecular biophysics at IRB Barcelona, where he studies the involvement of intrinsically disordered domains in disease and how to inhibit their functions with drug-like small molecules. Recently, he co-founded the company Nuage Therapeutics, which develops drugs targeting intrinsically disordered targets for oncolog

Summary - $100,000. Investigating the role of CD38 in metabolic dysregulation in Kennedy’s Disease: The energy that skeletal muscles need to function well with strenuous activity is greatly reduced in models of Kennedy’s Disease. Our aim is to identify therapeutic targets that will help fix metabolism in skeletal muscle to help increase this energy and improve muscle function in Kennedy’s Disease.

Bio: Heather L. Montie, PhD
Bachelor of Science (BS), Aquinas College, Grand Rapids, MI (Biology) (2000)
PhD Wayne State University, Detroit, MI (Physiology) (2005) (Thesis advisor: Donald DeGracia, PhD)
Postdoctoral Fellowship studying Kennedy’s Disease (SBMA), Thomas Jefferson University (2005-2013) (postdoctoral advisor, Diane E. Merry, PhD)
Prostate Cancer Foundation-Young Investigator, Postdoctoral Fellowship, Thomas Jefferson University, (2011 – 2013) (postdoctoral advisors, Diane E. Merry, PhD and Karen E. Knudsen, PhD)
Assistant Professor, Department of Bio-Medical Sciences, Philadelphia College of Osteopathic Medicine, (2013-2018)
Associate Professor, Department of Bio-Medical Sciences, Philadelphia College of Osteopathic Medicine, (2018-present)

Summary - $75,000. Investigating differences in polyQ-AR genomic activity leading to muscle atrophy in SBMA: At the heart of Kennedy’s Disease (KD) pathogenesis is the potent reduction of core muscle genes that encode contractile proteins, unsurprisingly leading to muscle loss, but we do not yet fully understand how polyglutamine-expanded AR (polyQ-AR) causes this. We and others have observed that in muscle of KD mouse models, the activity of a transcription factor critically important for sustained muscle gene expression called MEF2 becomes highly defective. MRF4, another muscle transcription factor, is known to repress the activity of MEF2 to prevent uncontrolled muscle growth, and knockdown of MRF4 in muscle cells grown in a dish causes a reduction in polyQ-AR protein levels. This study will determine if MRF4 is involved in KD muscle loss by assessing if disease course is altered in model mice that lack the MRF4 gene. We will also apply cutting-edge genomic techniques to investigate where in the genome of mouse muscle AR and polyQ-AR is binding, and whether those patterns are affected by loss of MRF4. These experiments will provide critical insight into how AR’s interaction with the genome of fully mature, physiological muscle cells is altered by the polyglutamine expansion and whether MRF4 mediates this alteration.

Bio: Anastasia has been studying KD since 2016, when she joined Dr. Albert La Spada’s lab as a first year Biomedical Sciences graduate student at UC San Diego. Coming from a research background in skeletal muscle regeneration and muscular dystrophy, she was instantly awestruck by a 2015 lecture by Dr. Constanza Cortes, then a postdoc in the La Spada lab, in which Dr. Cortes presented their findings on the requirement of polyglutamine-expanded AR expression in skeletal muscle as being necessary for both muscle and motor neuron degeneration. Now a postdoc herself at UC Irvine, she continues to be strongly committed to solving the paradox of KD: despite the well-established pro-hypertrophic effect of androgen signaling and the fact that even polyQ-AR seems to correctly orchestrate male development — including the increased accumulation of muscle mass and strength during male adolescence, why does polyQ-AR instead cause muscle atrophy at older ages? Anastasia hopes to continue working on this critically important question to help the men afflicted with KD and their families in the future in her own lab as an independent investigator, building off the exceptional mentorship and support of Dr. La Spada and the KDA community. Originally from St. Petersburg, Russia, Anastasia has been happy to call SoCal home for over 16 years since starting her undergraduate studies at the University of San Diego. In her free time, she enjoys baking for the lab, supporting the San Diego Zoo Wildlife Alliance, and training to compete in powerlifting.

2022 Grant & Fellowship Awards.

Award recipients are listed below.

In 2022, the KDA awarded two Waite-Griffin SBMA Fellowships, named in honor of the
people who founded the KDA. This is a one-year stipend of $75,000 for a junior PhD or MD
interested in a career in SBMA research and/or patient care. An additional $2,000 is
provided for travel and/or educational expenses. The awardee is expected to devote at least
70% of their time to SBMA research. The fellowship may be extended with demonstrated
progress in SBMA research. Following is a summary of the 2022 Waite-Griffin Fellowships

Developing an imaging biomarker in spinal and bulbar muscular atrophy (SBMA)
Abdullah AlQahtani, MD, MPH
Senior Clinical Research Fellow, NGB, NINDS

Candidate therapeutic strategies have been tested in preclinical models of SBMA, and
potential disease-modifying therapies will soon be evaluated in future clinical trials.
However, without appropriate biomarkers to assess disease progression reliably over a short
period of time, studies would require a large sample size and long duration to evaluate
efficacy. The goal of this study is to identify neuromuscular ultrasound (NMU) parameters
that serve as sensitive, reproducible, and cost-effective disease biomarkers for evaluating
efficacy in future therapeutic studies in spinal and bulbar muscular atrophy (SBMA). In
addition, the project will develop an ultrasound protocol to be used by neuromuscular
specialists in clinical practice to improve diagnostic accuracy and result in an earlier
diagnosis.

Using Drosophila exercise for therapeutic discovery in Kennedy’s Disease
Alyson Sujkowski, PhD

Endurance exercise is a potent intervention with widespread benefits proven to reduce
disease incidence across species. While endurance exercise supports neural plasticity,
enhanced memory, and reduced neurodegeneration, less is known about the effect of
chronic exercise on the progression of movement disorders like Kennedy’s Disease (KD).
Initial work has revealed protection of speed and maximal lifespan in exercised KD model
flies. Based on these preliminary observations, there are two specific aims. First, evaluate
the role of endurance exercise on a broad spectrum of KD phenotypes and second,
determine molecular mechanisms of protection from exercise that may be leveraged in the
future toward the development of targeted therapeutics.

In 2021, research grants were awarded totaling $175,000.

Award recipients are listed below as well.

Carlo Rinaldi, Oxford University ($75,000 for one year)
We plan to elucidate polyQ AR transcriptional altered activity and its role in SBMA pathogenesis, filling a fundamental gap in the understanding of this disease, and to unravel the therapeutic mechanism of action of AR45, a naturally-occurring AR isoform able to fine-tune AR transcriptional activity. Ultimately our goal is to bring a gene therapy approach based on therapeutic delivery of AR45 into first-in-man clinical testing for SBMA patients.

Shinichiro Yamada, Nagoya University: ($50,000 per year for two years)
Most patients with SBMA experience cold exposure, a worsening of muscle movement under cold temperature, which is caused by muscle membrane hyperexcitability due to abnormal sodium current alteration. Based on the clinical and basic studies, we carried out a placebo-controlled, randomized, double-blind, multicenter, crossover exploratory clinical study of the efficacy and safety of mexiletine hydrochloride, a sodium channel blocker, in SBMA patients. ALSFRS-R which reflect comprehensive motor function and quantitative muscle strength in SBMA patients were tend to be improved in the mexiletine group. Therefore, we will prepare a confirmatory clinical trial with change of ALSFRS-R as the primary endpoint. This study will be the first trial to confirm the efficacy of mexiletine hydrochloride administration in SBMA patients.

In this proposal, we are also planning a biomarker study in parallel to support the results of the clinical trials. We will measure urine titin and serum neurofilament light chain (NfL) as a biomarker of motor neuron degeneration in the patients with SBMA and female carriers in SBMA that may reflect early pathophysiology of SBMA patients.

2020 - Four research grants were awarded totaling $196,200. Award recipients are listed below. 

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.