It takes a dedicated team of researchers and several funding sources to get a treatment/cure to human clinical trial. Miracle For Madison and Friends Fund at The Ohio State University has been supporting Dr. Arthur Burghes's SMA research lab since 1998 and is used to pioneer SMA research work that is highly innovative and very risky. This type of research, is not funded by NIH, but when successful and is shown that it works, the researchers can then seek additional funding from NIH or the various SMA organizations to move the research forward.
When we first heard about a novel approach to noninvasive gene delivery in 2006, we became very excited and hopeful about the potential outcome this could have and wanted to help. http://researchnews.osu.edu/archive/newvect.htm -published 2006
The Kaspar Lab at The Research Institute at Nationwide Children's Hospital discovered that a single injection of self complimentary AAV9 vector (scAAV9) with green fluorescent protein (GFP) crossed the blood brain barrier (BBB) in neonatal mice and targeted expression in motor neurons. In regards to SMA, increased expression of the missing survival motor neuron gene (SMN) in lower motor neurons (LMNs) may have therapeutic benefits. Their results suggested that with a single injection, they may be able to effectively restore SMN expression levels in LMNs.
http://www.miracleformadison.org/archive/foustetalnaturebiotech.pdf -study published 2008
This discovery led to the development and collaboration of the SMA Gene Therapy program that now exists between the Burghes and Kaspar labs. Miracle For Madison and Friends began funding this innovative and risky idea through the Burghes lab at OSU with additional support from NIH to both labs. Dr. Brian Kaspar was invited to our annual fundraiser Madison's Angels at the End Zone in 2007 and 2008 to update families and donors about this groundbreaking research. The Delta 7 SMA mouse model created in the Burghes lab several years earlier was used for the next phase. The SMN1 gene was injected via the scAAV9 viral vector into the SMA mice at one day of age and resulted in complete "rescue" or reversal of the disease SMA. The treated mice showed no signs of SMA, gained weight and lived longer than any other drug or treatment being developed. Testing was also done on a larger and older animal, a non human primate and the "window of time" was extended to show the viral vector could still cross the BBB and target motor neurons giving hope to older patients living with the disease.
http://researchnews.osu.edu/archive/smnrescue.htm -published 2010
The data was quite impressive! The proof of concept was already there. The next 2 years would involve the required safety and toxicology studies needed before FDA would give approval to move on to human clinical trial. Additional funding came in for these studies from Families of SMA, FightSMA, Gwendolyn Strong Foundation and Sophias Cure Foundation and their partners along with the Pepsi Refresh grant which provided the cost for production of sufficient amounts of scAAV9. A project such as this is very expensive and never fully funded. There are always additional questions & other critical studies being done. Miracle For Madison & Friends support extended to both labs in helping with addressing FDA questions in the mice, creating various mouse and pig models of various types of SMA, understanding the complexity of the SMN protein and it's role throughout the body and additional avenues such as intrathecal or CNS delivery.
http://m.hmg.oxfordjournals.org/content/19/20/3895.full
With the preclinical studies now complete that brings this program to step 1 of 3 in gaining approval to move systemic delivery of scAAV9-SMN forward to human clinical trial. On December 4th, 2012, Dr. Jerry Mendell, Dr. Brian Kaspar, Dr. Arthur Burghes and Dr. John Kissel presented their data and proposal to the RAC- Recombinant DNA Advisory Committee at NIH. The RAC was very impressed and gave a positive unanimous decision and approval to move forward with a submission to FDA. Each institution has it's own review board so IRB approval will also need to be obtained before moving into the clinic. This video is the entire Day 1 of the RAC meeting and SMA begins around 98 minutes in from the start. Learn more about SMA and see this amazing data along with personal stories from several incredible SMA families:
http://videocast.nih.gov/summary.asp?Live=12202&bhcp=1
Many more exciting new therapies are being developed in both labs with the hope of moving into the clinic. The goal is to find an effective treatment for those of all ages and types of SMA. As you can see it takes many individuals, families, groups and organizations (big and small) along with the researchers to come together to make a MIRACLE happen. Keep on raising funds and spreading awareness. Continue to click on those links to vote. Share to the world that there is HOPE and someday soon no child will have to suffer loss of mobility or life because of SMA.
We THANK YOU and everyone involved for your part in helping a MIRACLE!
Always BELIEVE!
http://miracleformadison.blogspot.com/
