The study was conducted
in 121 children affected with spinal muscle atrophy to evaluate the efficacy
and safety of nusinersen
. While some children received
nusinersen, others received a placebo that served as a control. The scientists
evaluated the motor functions based on the Hammersmith Infant Neurological
Examination and survival based on the time to death or the use of permanent assisted
ventilation. Over a period of 13 months, the scientists found that:
- Progress in motor
function was noted in 41 percent of children who received nusinersen. A total of 37 of 73 infants showed an
improvement, in contrast to none among those who did not receive the
medication. Several children who received the treatment showed
movements like kicking, head control, rolling over, sitting, and standing.
- The children who received treatment had a 63 percent
lower risk of death and lesser chances of being put on permanent assisted
- The children who
were treated earlier experienced better benefits as compared to those who
did not receive nusinersen.
- The adverse
effects were similar in the two groups. Nusinersen was not associated with
any severe adverse effects in the study.
Nusinersen has recently
received approval by the US Food and Drug Administration for use in patients
with spinal muscle atrophy.
Spinal Muscle Atrophy
Spinal muscle atrophy is
a rare genetic condition that causes muscle weakness and wasting of the
The condition occurs due to an abnormal
or missing gene called the survival motor neuron gene 1 (SMN1)
chromosome number 5. This results in a problem in the nerves supplying the
muscles of the limbs and other muscles under voluntary control. As a result,
the muscles cannot be used and thin out.
Atrophy of the swallowing and breathing muscles often results in
repeated respiratory tract infections. Spinal muscle atrophy is of three types
- type I which appears at birth or within a few months after birth, type II
which appears between 6 to 18 months of age, and type III which appears at a
later age, between 2 and 17 years. Type I disease is the most serious form of
the condition with children usually succumbing to the disease within two years
of age, usually due to frequent lung infections.
‘Nusinersen, a drug that has been recently approved for the treatment of spinal muscle atrophy, improves muscle function and prolongs life in spinal muscle atrophy patients.’
Spinal muscle atrophy is
inherited in an autosomal recessive pattern. Thus, the defective gene should be
present on chromosome number 5 from both parents for the defect to be evident.
Patients with a single defective gene do not suffer from the condition, but can
pass it on to their progeny.
Till the recent approval
of nusinersen, treatment for spinal muscle atrophy was mainly symptomatic.
During symptomatic treatment, muscle relaxants are used to relieve the spasms,
while other drugs are used to reduce salivary secretions. In addition, physical
and occupational therapy are used to improve the patient's condition.
Nusinersen is a small
fragment of DNA (an oligonucleotide) that helps to increase the production of
the SMN protein and thus replace the missing protein in patients with spinal
muscle atrophy. It is administered through an intrathecal injection directly
into the cerebrospinal fluid, the fluid around the brain and the spinal cord.
It has been approved for the treatment of all types of spinal muscle atrophy
since it has shown benefit in the most serious form of the condition. It is
administered in a dose of 12 mg every 14 days for the first three doses, while
the fourth dose is administered 30 days after the third dose. Thereafter, the
injection is administered once every four months. It has caused reactions like
upper or lower respiratory infections and constipation. Since oligonucleotides
have been associated with adverse effects like bleeding and clotting problems
and kidney damage, nusinersen may also carry the risk of these complications.
- Finkel, Richard S, et al. "Nusinersen versus Sham Control in Infantile-Onset Spinal Muscular Atrophy." New England Journal of Medicine (2017): 2 Nov. 2017. N Engl J Med 2017; 377:1723-1732. DOI: 10.1056/NEJMoa1702752
- Spinal Muscular Atrophy Information Page - (https:www.ninds.nih.gov/Disorders/All-Disorders/Spinal-Muscular-Atrophy-Information-Page)