Novartis, one of the world’s largest pharmaceutical companies, is entering SMA Gene Therapy by acquiring AveXis, an American company for a deal that involves $8.2 billion in cash. This means that the possible treatment for spinal muscular atrophy, its related research, and other developments under AveXis will now be owned by Novartis. In the past, the company made headlines by announcing its clinical trials for gene editing in babies and children afflicted by SMA. The board of directors unanimously approved the deal, sealing the multi-billion dollar merger of two pharmaceutical companies.
SMA is a disease that affects the nervous system that impairs voluntary muscular movement. It is characterized and caused by a loss of motor neurons and progressive muscle wasting that causes early death among patients with the said disease. Around 1 out of 6,000 to 10,000 children are afflicted by SMA. The disease is usually linked to a mutation in the body’s SMN1 gene. Our body which consists of 23 pairs of chromosomes has two identical genes located in chromosome 5 called SMN1 and SMN2. For healthy bodies, the SMN1 codes the survival of motor neuron protein, which plays a very integral part in the survival of our motor neurons and plays a big part in either directly or indirectly controlling our organs, muscles, and glands. However, for individuals with SMA, the case seems to be much worse: the SM1 gene is mutated, making it incorrectly code the SMN, which will not allow them to function properly the way the genes in healthy humans do. This is due to a deletion or a mutation. Later on, the reduced availability of SMN results in the death of neuron cells in the spinal cord, and most notably, our brain. The muscles that greatly depend on these motor neurons will suffer from denervation, which will later on make their central nervous systems deteriorate. These denervated muscles eventually undergo atrophy.
The manifestation of SMA in humans can start in the late part of a woman's pregnancy due to reduced or even no fetal movements. The symptoms of this disease are critical that it could eventually lead to death in weeks. SMA is an inherited disorder.
There are five types of SMA, all of which greatly affect one’s health. For example, the worst type, type 0, happens less than six months after the birth of the child. Meanwhile, Type 1, which is the most common, kills 68 percent of children before their second birthday, and 82 percent of children with SMA Type 1 die before their fourth birthday, while the Type 2 disease, which occurs between 7 to 18 months after birth, can live until adult life when cared upon by professionals. The fourth type, Type 3, happens later than 18 months since the child’s birth, with a lifespan which is the same as the rest of the population. However, the fifth type, SMA Type 4, occurs in adults in which their life expectancy is not affected and can live unaided until the age of 60.
While the SMA Types are separated by age varieties, the symptoms also differ from one point to another. However, a book released by Oskoui, Darras, and DeVivo in 2017 has outlined the general symptoms, regardless of type, as follows:
|muscle in the arm/ Photo via Getty Images Bank|
Areflexia, particularly in extremities
Overall muscle weakness, poor muscle tone, limpness or a tendency to flop
Difficulty achieving developmental milestones, difficulty sitting/standing/walking
In small children: adopting a frog-leg position when sitting (hips abducted and knees flexed)
Loss of strength of the respiratory muscles: weak cough, weak cry (infants), accumulation of secretions in the lungs or throat, respiratory distress
Bell-shaped torso (caused by using only abdominal muscles for respiration) in severe SMA type
Fasciculations (twitching) of the tongue
Difficulty sucking or swallowing, poor feeding
For years now, AveXis has started to conduct research and experiments pertaining to the treatment of SMA patients. Five clinical trials, either ongoing or soon to be done, are planned for their AVXS-101, which will decide as to whether gene therapy will play a very important role in SMA treatment in children and adults or not. The AVXS-101 contains the SMN gene defective in people afflicted by SMA, and will target the motor neurons in the body. Considered as “safe” and a one-time treatment, the company showed a promising result in its first trials and has decided to conduct a Phase 3 series of trials that will be greatly influential in securing approvals from the US Food and Drug Agency and European Medicines Agency. According to Sukumar Nagendran, AveXis, Chief Medical Officer, medical experts alike are interested to know the future of AVXS-101. “What was remarkable and what we consider transformative... is that we had 100-percent survival of children at 13.6 months of age, and 100-percent survival of the children at 20 months of age,” Nagendran said in an interview.