Some Science Behind the News...(by Michael)

Dr. Brian Kaspar

The news that Dr. Kaspar's SMA research has been granted FDA approval to move forward with human clinical trials spread rapidly through the SMA Community and naturally found itself among the general public through Facebook, Twitter, blogs, emails, texts, phone calls, and personal encounters. To say that this news is big would be a gross understatement.  It's more than big...much more.

Dr. Kaspar and his staff are obviously major players in this development.  But there are more...many more.  From the very first person ever diagnosed with SMA to the latest; from the first fundraiser to the most recent.  The efforts, trials, sufferings, and triumphs of millions of people have brought forth this moment.  A moment of  increased hope for those afflicted with SMA.

I am grateful, as a parent of a child with SMA, for the goodness found in people.  From that goodness springs the seeds of hope.  And from that hope the seeds are nurtured.  That nurturing results in the seeds sprouting.  From there the seeds will flourish, bearing fruit in the form of life for anyone diagnosed with SMA.  The life they otherwise wouldn't have experienced.

Yes, there is much needed work still to be accomplished.  This is really only the beginning.  Hopefully the beginning of the end for SMA. 

So how does Dr. Kaspar's approach work?  Good question.

Here's a quick explanation:

• SMA is a result of a missing, mutated, or deleted gene known as SMN1.
• SMN1 produces a protein called SMN (Survival of Motor Neuron).  
• The lack of the SMN1 gene (and its protein) causes motor neuron death and in turn, muscle atrophy. 
• The SMN1 gene is located on chromosome #5.
• The cells that use the SMN1 gene are located primarily in the spinal cord.
• The spinal cord is protected by cerebrospinal fluid which (among other functions) creates a barrier (called a blood-brain barrier) against foreign intrusions.
• Therefore, delivering medications (or anything intravenously) to the cells in the spinal cord is extremely difficult, to say the least.
• Dr. Kaspar needed something that would act as a transporter (known as a "vector") for the SMN1 gene so it could be delivered to the cells in the spinal cord.
• A virus, known as AAV9, can pass the blood-brain barrier and enter the targeted cells.  [AAV9 is a "small virus that infects primate species and is not known to cause disease" {FSMA Compass; Spring 2012}].
• So now AAV9 can be the "vector" that is needed!
• They will inject a patient with the AAV9 virus (that is "carrying" the SMN1 gene) so it "infects" the target cells in the spinal cord.
• The AAV9 virus itself will not harm the patient.
• The SMN1 gene that has been "carried" in, however, reproduces itself naturally in the target cells.
• Once the cells have the necessary SMN1 gene, the required SMN protein can be produced and the motor neurons will be able to survive; hence no SMA!

Below:  "A new gene is injected into an adenovirus vector [such as AAV9], which is used to introduce the modified DNA [such as SMN1] into a human cell. If the treatment is successful, the new gene will make a functional protein."

Picture courtesy of Genetics Home Reference (http://ghr.nlm.nih.gov/)

Implications:

• For newly diagnosed patients, this would be a cure since doctors could introduce the "new" SMN1 gene immediately and halt any motor neuron death.
• For people who have already been diagnosed this would hopefully stop any further progression of the disease...this theory is yet to be verified.  Only time will tell.

What Now?

For the SMA Community this is a time of holding our collective breath.  We wait.  We pray.  We hope.  We watch every aspect of the human clinical trials.  We also continue to live our lives with SMA.  For so many, much damage has already been done to our kids.  Sadly, SMA will still take the lives of many people of all ages before it is all said and done. 

If this treatment/cure proves to be everything we hope it to be, there will be many people who have SMA now that will still need a great deal of assistance on many levels.  What drives the hope, however, is that those people with SMA today will hopefully live a longer life than they would have if not for Dr. Kaspar's research.

The first part of 2014 will be a whirlwind of emotions and anticipation.   Only time will tell and only God will reveal.