Spinal Muscle Atrophy (SMA) is a nasty genetic disease. However, advances in medical research has brought a drug to the market with a high cost. Without a doubt the debate will rage as to whether the cost of treatment is worth the life it is saving. To add a little bit of perspective, about 1 in 10,000 babies are born with spinal muscular atrophy. This equates to about 400 a year in the United States. SMA (#spinalmuscleatrophy) is among the leading genetic causes of death in infants under the age of 2. When you see a child with this disease, your heart goes out to them.
What is Spinal Muscle Atrophy?
Spinal Muscle Atrophy is a genetic disease with a flaw in the SMN1 gene which is located in chromosome 5. The SMN1 gene encodes the protein SMN which are found in all eukaryotic cells. Eukaryotic cells are defined as cells that have a nucleus enclosed within membranes. These cells are necessary for the survival of motor neurons which are located in the spinal cord, motor cortex of the brain and brainstem. These neurons are responsible for muscle strength as well as voluntary muscle movement. So any protein deficiency for these neurons will result in muscle atrophy.
This loss can be partially offset by the presence of neighboring SMN2 genes, which are similar in structure to SMN1 genes. Most of the proteins made from SMN2 genes are short and have no function, however, some are normal. In chromosome 5-related SMA, the more copies of the SMN2 gene that a person has, the more functional SMN protein is available, the later the onset of disease symptoms, and the milder the disease course is likely to be.
The scientific term for muscle atrophy is defined as a decrease in the mass or weight of muscles. This can be defined several ways including muscle weakness from lack of use. The key aspect is if you don’t use your muscles, they tend to weaken, lose weight and make a person incapable of moving. This is why a lot of doctors now have their patients move about after surgery. They want their patients to be active as possible as soon as is feasible, despite sutures, wounds, broken bones and pain. Being in a hospital bed for extended periods of time is actually bad for you.
There is no one size fits all for spinal muscular atrophies. All are genetic mutations but there are 4 main types associated with spinal muscle atrophy . The various types carry symptoms that range from mild to severe and are based on age. First is called Spinal Muscle Atrophy Type 1. Other names associated with this type is infantile onset or Werdnig Hoffman Disease. These symptoms are present at birth or by 6 months. Babies have general muscle weakness, a weak cry or trouble breathing. Additionally, babies often have difficulty swallowing, sucking, and don’t reach the developmental milestone of being able to sit up unassisted. These babies tend to have two copies of the SMN2 gene, one on each chromosome 5.
Spinal Muscle Atrophy Type 2 or intermediate SMA begins between the ages of 7 and 18 months and before the child can stand or walk independently. Children generally have at least three SMN2 genes. Spinal Muscle Atrophy Type 3 begins after 18 months and children can stand and walk independently with help (cane or walker). Spinal Muscle Atrophy Type 4 (Kugelberg Welander Disease) is diagnosed in adulthood with mild symptoms. Adults with Spinal Muscle Atrophy Types 3 and 4 generally have between four and eight SMN2 genes. This quantity of genes allow for a fair amount of full-length SMN protein to be produced. types 3 & 4 generally lead normal life spans.
As you can see, the earlier in life the genetic defect is expressed, the lesser the chance of living a normal life. Thanks to medical upgrades over time, children with SMA 1 can survive longer with the help of medical devices. The concern is usually when muscles that affect breathing are impacted. Weak respiratory muscles are a concern especially during flu season since any infection can be life threatening. Typically all SMA types tend to affect muscles closer to the center of the body. The farther away from the center, the less impacted. So as an example, thigh muscles are impacted before those the lower legs and feet. Hands tend to remain the strongest due to distance which helps maintain some of the basic functions of modern life.
A second concern involves the spinal curvature of patients. Some know it as scoliosis which is a side to side curvature of the spine. The spine is flexible in nature and are supported by spinal muscles. Any weakness in the muscles will interfere with position and mobility as well as breathing. In addition, you have body image perceptions which affect mental and self-confidence. During early childhood, not much can be done and treatment is the use of a brace until surgery age is reached. Surgery involves surgically straightening and fusing the spine to correct for scoliosis.
A New Medical Hope
Recently, the FDA has approved the first drug to treat patients with spinal muscular atrophy. It is the first of its kind and it comes with a large price tag. The prescription drug is called Spiranza (nusinersen). Biogen, which is licensing Spinraza from Ionis Pharmaceuticals has priced it at $125,000 per dose. The five or six doses required for the first year will come to $625,000 to $750,000. On top of that, three additional doses are need each year at a retail price of $375,000 annually. The doses have to be taken for the rest of a patients life. It will be one of the most expensive drugs on the market. So if you squirmed in your seat at those numbers imagine what insurance companies are doing.
Here is where the math gets eye-popping for those unfortunate children who are born with this disease. Keep in mind that this is through no fault of their own nor their parents. Year one $750,000. Average lifetime of a person is 85 in the US. So 84 x $375,000 plus $750,000 equals $32, 250, 000. I had to check the number several times on the calculator. What do you think the chances are of an insurance company covering this medication. Consider the public fight going on today over healthcare. The child would be covered until 26 under the parents plan. The he or she would be responsible for $21,000,000. So which insurance company wants to sign up for a pre-existing condition with the potential for a $21 million dollar loss. Now try telling the parents that their child is better off disabled.
Spinraza (nusinersen) is considered an antisense oglionucleotide drug. Allow me to explain. In your genetic makeup, you have strands of DNA and RNA that are used to make proteins for various functions. When one of these strands get broken or corrupted, proteins no longer get made. Think of it also like your computer. You have all of those files and lines of code in the background that help make it function. When a file gets corrupted, funky things start to happen to the computer until that file is updated and corrected.
Spinraza works by injecting short synthesized DNA or RNA strands into the central nervous system through your spine. These synthesized strands are then absorbed into your system and analyzed by your body. Since the sequence are specific, they tend to get attached to a targeted gene. The target is the SMN2 gene which is altered and converted into an SMN1 gene. If you remember, the SMN2 gene does make some of the missing proteins. Once the alteration is made, production begins of the missing protein. In essence you are altering your genetic code and having other parts of the gene do the work of the defective gene.
Overall, your chromosomes will always have the defective gene. So once you stop adding the synthesized material, you will go back to how you were. Which is why you need constant injections to keep updating your genetic make-up. This technology is relatively new and expensive. Since SMA is a rare disease, the FDA granted this drug orphan status to move approvals along quicker.
Side Effects Of Spinraza
There are side effects associated with its use. The most common include lower and upper respiratory infections, constipation, headache, back pain, and post-lumbar puncture syndrome. More serious side effects have been found such as increased risk of bleeding complications and low blood platelet counts. Constant kidney monitoring with blood work is required due to the toxicity to the kidneys. Prevention of any kidney damage including fatal acute kidney inflammation is important.
Although more information is needed about Spinraza side effects, its benefits are very clear. During the clinical trials, children who did not receive the placebo saw rapid improvement. In an analysis of 82 infants in the clinical trial that led to the approval, 40 percent of babies on the drug reached milestones such as sitting, crawling and walking. The progression of the disease seemed to have stopped. None of the babies that received a placebo did. Keep in mind that no one knew who was receiving the actual drug. It became that obvious.
Where Do We Go From Here?
This new genetic technology for treating rare diseases is amazing. This type of research is being done in diseases such as cancer, diabetes, ALS, Duchenne muscular dystrophy, asthma and arthritis. Cost seems to be the limiting factor. Already countries like Denmark only allow the use to a small amount of patients in Spinal Muscle Atrophy Type 1. Norway meanwhile has approved the medication for patients under the age of 18. I am also assuming that they are not paying the full price probably since they buy in bulk.
The question becomes what is your child’s life worth? What is his or her potential versus the multi million dollar price tag. Ten years from now it might get cheaper to produce but for an infant, that is too late. Thoughts?