INFORMATION FOR PATIENTS AND FAMILIES

We're working relentlessly to bring gene therapy to patients and families affected by life-threatening genetic diseases, like spinal muscular atrophy (SMA). We believe our commitment to advancing gene-based medicine can help in the fight against devastating hereditary diseases.

The Hereditary Nature of SMA

Inheriting a mutated or missing SMN1 gene prevents the body from adequately producing the SMN (survival motor neuron) protein—which is critical to the function of nerves that control our muscles—leading to the debilitating and often fatal muscle weakness caused by SMA.

Defective SMN1: Inheritable Odds

People typically receive one copy of the SMN1 gene from each parent. Only one fully functioning SMN1 gene is required to produce adequate levels of the SMN protein. Since SMA is a recessive trait, both parents may be healthy but they can still carry and hand down a mutated or missing SMN1 gene—affecting their children.

1 in 50 Americans are carriers of a defective SMN1 gene

Two carriers have a 25% chance of having a child with SMA

SMN2: A Secondary source of SMN

Human DNA contains a second gene that codes for the SMN protein. This gene, SMN2, may be present in more than 2 copies but unlike the SMN1 gene, SMN2 contains an exon (Exon7) that is removed from the mRNA coding for the SMN protein resulting in an unstable and nonfunctional SMN protein approximately 90% of the time. While the level of functional SMN protein produced by an SMA patient's SMN2 genes are generally insufficient to prevent loss of motor neuron function, they do correlate to disease onset and severity.

Up to 90% of SMN protein produced by the SMN2 gene is non-functional

SMN2 modifies SMA severity— the more copies there are, the less severe the disease is

The Advanced Science of Gene Therapy

As an experimental technique for correcting defective genes that are responsible for disease development, gene therapy may be used to encode a therapeutic protein that improves cellular function—such as supplementing SMN protein expression by introducing a fully functional SMN gene into an SMA patient's cells.

Here's a simple diagram of how gene therapy works:

 

Modified
Viral DNA
Transgene Modified
Viral DNA

Step 1

The vector—an altered adeno-associated virus that can't reproduce—is used to deliver a new gene. The vector binds to the patient's cell membrane.

Step 2

The vector breaks down, allowing the new gene to be injected into the cell nucleus.

Step 3

With the new gene in place, the patient's cell begins producing the required protein.

Our approach focuses on treating SMA at the source

AVXS-101 is our clinical-stage gene therapy for the treatment of SMA Type 1. We're targeting the SMN gene in order to restore the body's SMN protein production to an adequate level by using a:

  • Recombinant AAV9 capsid shell that acts as a transgene delivery system
  • Stable, fully functioning human SMN transgene
  • Self-complementary DNA technology to enable rapid onset of effect
  • Continuous promoter to activate the transgene to sustain SMN protein expression