Throughout history, neurodegenerative diseases have been among the most devastating diagnoses in the medical world. They include illnesses such as Parkinson’s, Dementia, Amyotrophic Lateral Sclerosis (ALS), and Spinal Muscular Atrophy (SMA). Progressive death of neurons leads to patients who suffer, often completely aware and sound minded, trapped inside a deteriorating body. Patients are presented with bleak prognoses because of one simple problem that no research has yet been able to solve; a neuron that dies cannot be fixed or replaced. Damage that these diseases do to the body is un-doable.
Typically, neurodegenerative disease affects the elderly, which is what makes SMA a particularly tragic diagnosis- types 1 and 2 affect infants while types 3 and 4 affect adolescents and young adults. While there is no cure for SMA, a treatment has emerged that offers patients and families hope for the first time. The drug Nusinersen, also known as Spinraza, is truly a miracle for sufferers of SMA. Never before has a drug been available that seemingly stops the progression of SMA in its tracks.
What causes SMA?
SMA is caused by a mutation in the SMN1 gene. SMN stands for survival motor neuron. This gene is responsible for producing survival motor neuron protein which is vital for the health of motor neurons. In patients with SMA, SMN1 can’t produce this protein and their motor neurons degenerate. This leads to paralysis, respiratory problems, and muscle wasting, to name a few symptoms. The gene SMN2 is very similar to SMN1, though it produces less protein. The SMN2 gene is functional in patients with SMA but does not provide them enough SMN protein to keep them healthy. This is because an exon (a piece of DNA or RNA that is meant to remain in the sequence) is spliced out of SMN2 during mRNA processing. The number of copies of SMN2 present in a person with SMA dictates their type of SMA and the severity of their symptoms. Type 1 SMA is severe and presents in infancy because only 2 copies of SMN2 are present on average. Type 4 SMA patients, however, typically have 4 copies of SMN2 and therefore the latest onset and least severe symptoms.
How does Spinraza work?
Spinraza works by increasing SMN2 activity to provide enough production of functional SMN protein to override the genetic defect. The drug is known as an antisense oligonucleotide (ASO). Proteins are synthesized from messenger RNA (mRNA). An ASO is a string of nucleotides that is able to bind to mRNA. Spinraza is able to bind so that the essential exon, which is normally lost, remains in SMN2. This allows SMN2 to produce enough SMN protein that it functions as SMN1 does in a healthy person.
In clinical trials, patients of a variety of ages and symptoms were treated with Spinraza. In a double-blind study of SMA patients who became symptomatic in infancy, 51% of those who received treatment saw drastically improved motor function and were able to reach motor milestones. Of those who received a sham treatment, 0% saw this kind of improvement. Patients who experienced a later onset of SMA also saw improvement in strength and motor function upon receiving Spinraza.
In some cases, children can be diagnosed with SMA prenatally due to siblings having it or parents being aware that they are carriers. In these cases, infants were able to receive Spinraza before symptoms appeared. This has allowed them to reach motor milestones previously unheard of in children with type 1 and 2 SMA. Some reports even say that their development while receiving the drug is parallel to the development of a healthy child.
Spinraza isn’t perfect; it requires a painful and inconvenient lumbar puncture for administration. This is because it is the only way for an ASO to cross the blood-brain barrier and be effective in the central nervous system. It is also one of the most expensive drugs in the world at $125,000 per injection. Despite these drawbacks, it is still a shockingly effective treatment.
Advances in medicine are made every day but the success of Spinraza remains one of the most significant developments in recent times. Neurodegenerative diseases are notoriously difficult to treat and uncurable. Spinraza isn’t a cure, it cannot reverse the damage already done to motor neurons, but it is a step in the right direction. The relief that the drug has brought patients and their families is priceless and Spinraza stands as a beacon of hope not only to the SMA community, but to the neurodegenerative disease community at large. It is a reminder that every hopeless diagnosis may only need some time before research catches up and produces the next unheard of treatment.