Work in the Lorson lab at the University of Missouri, the DiDonato lab at Northwestern University, and the Kaspar lab at Nationwide Children’s Hospital have recently shown functional and developmental cardiac defects in two severe models of spinal muscular atrophy (SMA). The studies were conducted with mouse models, not SMA patients, and all three were recently published in the journal Human Molecular Genetics.

According to Dr. Chris Lorson, FightSMA’s Science Director and also an author of one of the studies, “collectively these results highlight the importance of additional tissues in SMA that may contribute to the overall pathology in SMA - most likely in more severe cases. This is especially important when developing and testing potential therapeutics in SMA models and as novel compounds progress towards the clinic.”

Click the links below to read the article abstracts:

• Lorson Lab: Cardiac defects contribute to the pathology of spinal muscular atrophy models
• DiDonato Lab: Arrhythmia and cardiac defects are a feature of spinal muscular atrophy model mice
• Kaspar Lab: Early heart failure in the SMNΔ7 model of spinal muscular atrophy and correction by postnatal scAAV9-SMN delivery

Gwendolyn Strong Foundation Is Campaign Partner

RICHMOND, VA - Richmond-based FightSMA announced today a new fundraising campaign for spinal muscular atrophy (SMA) gene therapy, “Realizing the Dream.” FightSMA is collaborating with the Santa Barbara–based Gwendolyn Strong Foundation, to form a bi-coastal partnership with a common goal: to bring SMA gene therapy to clinical trial.

“Ten years ago, it would have been unheard of to say scientists were approaching a treatment or cure for spinal muscular atrophy,” said FightSMA President Martha Slay. “Today, the dream is being realized in some of the most prestigious labs across the country. Never before has there been such promise for SMA gene therapy.”

Beginning now and for the next three years, families and groups in the SMA community will raise funds to build a safe foundation, deliver genes to an SMA model, and produce adequate vector (gene delivery) supply. These efforts will support Dr. Brian Kaspar (pictured left) of Nationwide Children’s Hospital and The Ohio State University and other collaborating scientists.

FightSMA, working with the Gwendolyn Strong Foundation, a funding source for critical SMA science and awareness initiatives, invites the SMA community to make a decade-old dream come true. “Our SMA gene therapy program at Nationwide Children’s Hospital and the Ohio State University continues to show great promise for treating SMA patients,” said Dr. Kaspar.

FightSMA’s objective for the balance of 2010 is to complete funding for Phase One and for Year-One of Phase Two of the research program. “The first objective is to build a solid foundation of safety and to eliminate toxicity,” said Dr. Chris Lorson, FightSMA Science Director. Additionally, FightSMA plans to raise another $250,000 to fund the first year of Phase Two (Delivery & Efficacy). The “Realizing the Dream” program will be accomplished through a series of campaigns. Completing these two Phases will bring SMA gene therapy significantly closer to clinical trial.

FightSMA has been instrumental in helping to develop a gene therapy strategy to cure spinal muscular atrophy (SMA), including oligonucleotides and gene replacement vectors. The strides that SMA researchers have made in the gene therapy arena have provided insights into a range of genetic disorders, including other neurodegenerative disease (ALS/Lou Gehrig’s disease, myotonic dystrophy, Huntington disease) and other diseases such as Duchenne muscular dystrophy.

For more information on the FightSMA-Gwendolyn Strong Foundation partnership and “Realizing the Dream” campaign, visit www.fighsma.org or call 804-515-0080.

FightSMA was created to strategically accelerate the search for a treatment and cure for spinal muscular atrophy (SMA), the number-one inherited cause of infant death. The organization pursues this objective by raising awareness and funding for SMA research.

This month, the journal Human Molecular Genetics published a special issue focused on advancements in neurological and neurodegenerative diseases. Included in this issue is an article by FightSMA’s Science Director Dr. Chris Lorson and colleagues from his lab at the University of Missouri entitled “Spinal muscular atrophy: mechanisms and therapeutic strategies.”

The abstract:

Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disorder and a leading genetic cause of infantile mortality. SMA is caused by mutation or deletion of Survival Motor Neuron-1 (SMN1). The clinical features of the disease are caused by specific degeneration of α-motor neurons in the spinal cord, leading to muscle weakness, atrophy and, in the majority of cases, premature death. A highly homologous copy gene (SMN2) is retained in almost all SMA patients but fails to generate adequate levels of SMN protein due to its defective splicing pattern. The severity of the SMA phenotype is inversely correlated with SMN2 copy number and the level of full-length SMN protein produced by SMN2 (~10–15% compared with SMN1). The natural history of SMA has been altered over the past several decades, primarily through supportive care measures, but an effective treatment does not presently exist. However, the common genetic etiology and recent progress in pre-clinical models suggest that SMA is well-suited for the development of therapeutic regimens. We summarize recent advances in translational research that hold promise for the progression towards clinical trials.

For more information, click here.

The 2010 FightSMA Annual Conference, entitled “The Good Fight,” opened in yesterday, April 25th, at the L’Enfant Plaza Hotel in Washington, D.C with an international collection of researchers gathering to discuss spinal muscular atrophy (SMA) and related sciences. FightSMA’s Science Director, Dr. Chris Lorson, started off the meeting with a brief introduction before attendees heard from Dr. Kathy Swoboda from the University of Utah, Dr. Rashmi Kothary from Ottawa Health Research Institute, Dr. Livio Pellizzoni from the Columbia University Center for Motor Neuron Biology and Disease, and Dr. Allison Ebert University of Wisconsin-Madison. After dinner, Dr. Charlotte Sumner of the Johns Hopkins University School of Medicine, Dr. Barrington Burnett of National Institute of Neurological Disorders and Stroke, and Dr. Michael Sendtner from the University of Wurzburg (Germany). Topics of the evening included SMA clinical trials, mouse models, and iPS cells.

The researchers’ portion of the conference resumes today with additional presentations and discussions wrapping up shortly before the families and friends portion opens at 5:00PM with an introduction by FightSMA’s president, Martha Slay, and a Science Update by Dr. Lorson. This and the “Thriving with SMA” panel will be available by webcast, free of charge, for families and caregivers unable to attend the conference in person.

In less than two weeks, FightSMA will be returning to Washington, D.C. to host the 2010 FightSMA Annual Conference: The Good Fight. This meeting provides a unique setting for researchers investigating spinal muscular atrophy (SMA) and related conditions to discuss their work openly and chart a path forward. The Good Fight also brings together SMA patients, families, friends, and caregivers to learn about research being conducted around the world and to hear from health care professionals in fields important to the day-to-day lives of SMA patients.

The economy, illness, and other hardships can make travel difficult, or even impossible, for some. This is why FightSMA is pleased to once again offer SMA families, friends, doctors, and caregivers a way to access some of the content remotely. The Science Update by Dr. Chris Lorson (April 26th at 5:00PM EST) and the Thriving with SMA panel (April 26th at 6:30PM EST) will be available by live webcast. This access is offered for free by FightSMA and its conference sponsors. There is no limit to the number of viewers, and so, we ask you to share this information with other families affected by SMA and with your health care providers who would like to learn more about the disease.

For those who want to simply view the video, just visit the FightSMA Website. Anyone who would like to access the chat feature to ask questions will need to create an account on UStream, the video streaming service being used for the webcast. We recommend that viewers create their accounts and open the viewing webpage ahead of time to ensure that none of the presentations are missed.

We are very excited about our conference and anticipate an encouraging and very informative time together. We hope that you will attend and encourage your friends and health care providers to join us as well.

As she approaches the end of high school, Courtney Griffin is looking toward the next stage of her education: college. Like many students her age, she is touring universities, but unlike most, Courtney also has to consider accessibility and other factors because she has spinal muscular atrophy (SMA) type 3.

Recently, Courtney and her parents Terry and Deanna visited the University of Missouri, aka “Mizzou,” which is also the home-base of Dr. Chris Lorson, FightSMA’s Science Director. Dr. Lorson met with the Griffin Family and gave them a tour of his lab.

The Griffins sent this recap:

Our heartfelt thanks to Dr. Lorson for meeting with us and playing “Tour Guide Extraordinaire” at University of Missouri when we visited! We were in Columbia as an opportunity for Courtney to visit Mizzou’s gorgeous campus as part of her college search. Dr. Lorson showed us around the lab and introduced us to the many dedicated people working hard on the various SMA projects there.

We got a chuckle out of the fact that in his younger days, he used to play some hard-fought games of Ultimate Frisbee on the very spot where the Bond Life Sciences Center now stands - and where SMA research is progressing in earnest!

We had an incredibly productive day at Mizzou and we found an institution highly dedicated to accessibility, education, and research.

Thanks again Dr. Lorson!

Terry, Deanna, and Courtney Griffin

The FightSMA Annual Conference: The Good Fight is off to a great start. Opening last night, attendees heard from Dr. Arthur Burghes of Ohio State University, Dr. Livio Pellizzoni of the Columbia University Center for Motor Neuron Biology and Disease, and Dr. Rashmi Kothary of Ottawa Health Research Institute.

The last speaker of the night was Dr. Clive Svendsen. Dr. Svendsen, his team at the University of Wisconsin-Madison, and FightSMA Science Director Dr. Chris Lorson drew attention last year when they published the journal article “Induced pluripotent stem cells from a spinal muscular atrophy patient.” Work with induced pluripotent stem cells (IPS cells) and the potential promise that they hold for numerous diseases was so striking that Science declared it the 2008 Breakthrough of the Year .

 FB 19 [18:51m]: Play Now | Play in Popup | Download

This is part 2 of our 2009 State of the Disease Podcast for Spinal Muscular Atrophy, where we look back at the scientific advances in SMA research in 2008 and look forward to what might come in 2009.  This two-part series features the co-chairs of FightSMA’s scientific committee, Alex MacKenzie, M.D. (Director of the Children’s Hospital of Eastern Ontario Research Institute) and Chris Lorson, Ph. D. (Assistant Professor at the University of Missouri-Columbia).

In part one Alex and Chris discussed three of the research advances they picked as being the most significant in 2008.  In this episode, they  finish that discussion by highlighting the following 2008 findings:

• Exercise promotes motor unit development and survival in mild SMA mice
• A variety of RNA-based therapeutics that are moving in vivo
• SMA Standards of Care
  

We also tackle the future … what might come in 2009 in spinal muscular atrophy research.

If you haven’t listened to part one of this two-parter, it’s strongly suggested you visit this post, and listen there first!

To listen to this episode, you can use the Flash mp3 player above, load the Fighting Back Podcast Feed into your favorite feed reader, subscribe via iTunes or other podcast directories, or simply use the download link above to load the file onto your computer.  If you have feedback, a comment or question, or are interested in having Fighting Back tell your story, please contact page! You can also leave a message in the form of a comment on this blog as well.

 FB 18 [14:02m]: Play Now | Play in Popup | Download

2008 was an important year in spinal muscular atrophy research, as scientists and doctors continued their work to find a treatment or cure for the neuromuscular disease.  This episode of Fighting Back Podcast is the first part of our yearly “look back and look forward”.  This time we look back at 2008 and look forward to 2009 with the co-chairs of Fight SMA’s scientific committee, Alex MacKenzie, M.D. (Director of the Children’s Hospital of Eastern Ontario Research Institute) and Chris Lorson, Ph. D. (Assistant Professor at the University of Missouri-Columbia).

Before the podcast recording session, Dr. MacKenzie and Dr. Lorson forwarded their lists of what they believe to be the most important scientific findings in SMA research in 2008.  In this episode, we have a spirited discussion of the first three items on the list, including what they are and why they’re important.  The advances discussed in this episode are:

• A non-SMN modifier of disease: Plastin-3 (B. Wirth)
• Muscle vs nerve SMN rescue in SMA mice (A. Burghes)
• Nutritional supplement w/ TSA significantly increases SMA mouse survival (C. Sumner)

(Note: We are efforting links for each of these. Please check back!)

In part 2 of our State of the Disease Podcast for SMA, which will be released next week, we discuss the remaining items on the list, including the role of exercise promoting motor unit survival and the groundbreaking SMA Standards of Care that were released in 2008.  Drs. MacKenzie and Lorson also discuss the important findings they they hope will happen in 2009.

To listen to this episode, you can use the Flash mp3 player above, load the Fighting Back Podcast Feed into your favorite feed reader, subscribe via iTunes or other podcast directories, or simply use the download link above to load the file onto your computer.  If you have feedback, a comment or question, or are interested in having Fighting Back tell your story, please contact page! You can also leave a message in the form of a comment on this blog as well.

From the University of Missouri News Bureau:

MU Researchers Discover Target that Could Ease Spinal Muscular Atrophy Symptoms

Jan. 7, 2009
Story Contact: Kelsey Jackson, (573) 882-8353, JacksonKN@missouri.edu

COLUMBIA, Mo. – There is no cure for spinal muscular atrophy (SMA), a genetic disorder that causes the weakening of muscles and is the leading genetic cause of infant death, but University of Missouri researchers have discovered a new therapeutic target that improves deteriorating skeletal muscle tissue caused by SMA. The new therapy enhanced muscle strength, improved gross motor skills and increased the lifespan in a SMA model.

“This therapy does not directly target the disease-causing gene; instead it targets the pathways that affect muscle maintenance and growth,” said Chris Lorson, investigator in the Christopher S. Bond Life Sciences Center and associate professor of veterinary pathobiology in the MU College of Veterinary Medicine. “We administered a particular protein, follistatin, to SMA mouse models to determine if enhanced muscle mass impacts the symptoms of SMA. After treatment, the mice had increased muscle mass, gross motor function improvement and an increase in average life span of 30 percent.”

With the therapy, MU researchers inhibited myostatin, a protein that limits muscle tissue growth. Myostatin activity can be reduced significantly by enabling several proteins that bind to myostatin, including follistatin. When myostatin is inhibited, muscle mass and strength increase.

SMA is caused by the loss of survival motor neuron-1(SMN1). Humans have a nearly identical copy gene called SMN2. Because of a single molecular difference, SMN2 alone cannot compensate for the loss of SMN1.

“While most work in the SMA field has logically focused on targeting the SMN2 gene, the results of this study suggest that skeletal muscle is a viable therapeutic target that may reduce the severity of some SMA symptoms,” said Lorson, who also is the scientific director for FightSMA, a private spinal muscular atrophy research foundation in Richmond, Va. “Because follistatin does not alter the expression level of SMN protein, the most effective treatment would combine strategies that directly address the genetic defect in SMA as well as SMN-independent strategies that enhance skeletal muscle.”

The study, “Delivery of recombinant follistatin lessens disease severity in a mouse model of Spinal Muscular Atrophy,” was published online in the December issue of Human Molecular Genetics. The research team also consisted of graduate students Frankie Rose and Virginia Mattis, and Hans Rindt, an assistant research professor. Recently, Lorson was awarded a $370,000 grant from the Muscular Dystrophy Association to continue his research on the role of muscle in SMA.

Click here for the original news release. To read the study’s abstract, click here.