MDA Grant for Research on SBMA

The following article appears in NewsWise. Click on the link below to read the entire article.

Dr. Carlo Rinaldi Receives Co-Funded AANEM Foundation/MDA Grant for Research on Spinal and Bulbar Muscular Atrophy

 Carlo Rinaldi, MD, PhD, has been selected as the recipient of a development grant co-funded by the AANEM Foundation and the Muscular Dystrophy Association (MDA). Dr. Rinaldi, who works as an Associate Professor in the Department of Physiology, Anatomy and Genetics in the Division of Medical Sciences at the University of Oxford in the United Kingdom, will be using this funding to increase understanding of the pathophysiology of spinal and bulbar muscular atrophy (SBMA). SBMA is a neuromuscular disorder characterized by the degeneration of lower motor neurons and primary muscle atrophy. Dr. Rinaldi’s ultimate goal is to develop effective therapeutic treatments for this yet incurable condition.

Dr. Rinaldi’s research objective is to characterize the role of the androgen receptor (AR) isoform 2 on AR biology and its impact on SBMA toxicity. His central hypothesis is that AR45 is a key regulator of AR activity and represents a promising therapeutic target for SBMA.

“There is currently no treatment available for SBMA,” explained Dr. Rinaldi. “This research work has the potential to shed new light on the role of the AR isoforms in both health and disease, advance understanding of the mechanisms of pathogenesis in SBMA, and provide a new therapeutic target in close relationship with the disease-causing mutation.” 

“Dr. Rinaldi has the strong support of the Neuroscience community in Oxford to pursue his research into the mechanisms of motor neuron degeneration in SBMA,” noted Kevin Talbot, MB, PhD, FRCP, Head of the Division of Clinical Neurology and Professor of Motor Neuron Biology and Consultant Neurologist at John Radcliffe Hospital in Oxford. “This is a neglected area and he is in an excellent position to be a leader in this field, both within Europe and worldwide.” …

New Funding for SBMA Research

The MDA announced the funding of $9.9 million dollars in research grants. The grant below is for the study of Kennedy's Disease.

Carlo Rinaldi, Ph.D., associate professor and clinician scientist at the University of Oxford in England, was awarded an MDA Development Grant to study how variants in the gene of the androgen receptor (AR) protein cause spinal-bulbar muscular atrophy (SBMA) and investigate whether a novel antisense oligonucleotide therapy approach can target these toxic variants. The results of the study will provide a better understanding of SBMA disease mechanisms, as well as develop a new therapy potentially capable of treating the disease.

This work has potential implications for other diseases of the motor unit as well, including spinal muscular atrophy (SMA) and ALS. This grant is co-funded by the American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM).

Additional information was provided on another page:

“Better understanding of the underlying disease mechanisms, coupled with improvement of gene vector design, therapeutic gene selection, and methods of delivery, have made gene therapy a realistic option for neuromuscular conditions — and neurological diseases in general — for which no treatment option was available until few years ago. Many challenges still lie ahead, but we have good reasons to be very optimistic for the future.”

Carlo Rinaldi, associate professor and clinician scientist at the University of Oxford in England, was awarded an MDA Development Grant totaling $120,000 over 3 years to study the role of androgen receptor isoforms in SBMA pathogenesis and the potential as therapeutic targets. This grant is co-funded by the American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM).

Mutations in the gene encoding the androgen receptor (AR) protein cause spinal and bulbar muscular atrophy (SBMA). SBMA is an adult-onset neuromuscular condition affecting males with unmet clinical need. It is not undestood how mutations in AR lead to primary degeneration of motor neurons and muscle in patients. The activity of AR and other hormone receptors can be modulated in human cells by isoforms and/or splice variants, which may block or enhance their functions.

Dr. Rinaldi and colleagues plan to investigate the role of AR alternative isoforms in mediating SBMA toxicity. By revealing how these isoforms regulate AR activity in health and disease, researchers expect to better understand the mechanisms of disease in SBMA and provide a novel rational therapeutic target. If successful, the work could pinpoint tissue-specific targets for therapy development, with implications not only for SBMA but for other diseases of the motor unit as well, including spinal muscular atrophy and amyotrophoic lateral sclerosis.

Lecture by Dr Fischbeck at Oxford University

This article was posted by Colin Hopps on the KD-UK blog. I think most everyone will find it interesting.

"Prior to this lecture at Oxford, my understanding of KD has been superficial but after reading an explanation by Dr Fischbeck and attending his lecture at Oxford University I have a much better grasp.


We have a repeat of a CAG pattern in the Androgen Receptor gene on our X chromosome. If one has up to 36 repeats you will not have KD but 38 and above you will and generally the more repeats the earlier the onset and severity. These extra repeats cause us to produce a longer Androgen Receptor protein which isn’t good but in itself would not cause KD, it is the toxicity it causes to the neurons and muscle cells this in turn damages the cells and ultimately results in the death of these cells. Below is the more technical description, took me several hours and Wikipedia to get a basic understanding.


So what is happening in the world of research regarding treatment? Well there are research groups in America, Copenhagen, Padua, Nagoya and here in London and Oxford. There is research mainly in five areas. ..."


Link to the entire post:  Oxford Lecture Notes