Nusinersen and Spinal Muscular Atrophy

What is Spinal Muscular Atrophy?


Spinal muscular atrophy or SMA is a type of genetic disease that mainly affects the control of voluntary muscle movements. The disorder is caused by the loss of a special type of nerve cells known as motor neurons that are found in the spinal cord and also in the part (brainstem) that remains connected to the brain from the spinal cord.  When there is a loss of motor neurons it leads to atrophy or wasting of the muscles that weakens the regular activities like the movement of head, sitting up or crawling. If the condition of the spinal muscular atrophy is severe then it can badly affect the muscles that are used for swallowing and breathing. This disorder, if not properly diagnosed and treated may lead to early death.

Atrophy explained…

This disease is caused by a defect in the SMN1 gene that encodes the SMN which is a protein largely found in the eukaryotic cells. This protein is vital for the survival of the motor neurons in the spinal cord. When the level of this protein diminishes it results in the loss of functioning of the neuronal cells within the anterior horn of spinal cord as well as the consequent systematic atrophy of the skeletal muscles. Spinal muscular atrophy is manifested in different degrees of severity. Nevertheless, all of these types have one thing is common – progressive atrophy of skeletal muscles and impairment of normal mobility.

Primarily the respiratory and proximal muscles get affected and if not treated, at the then the other systems may get affected as well if not treated at the early onset. Statistics show that Spinal Muscular Atrophy is one of the most common genetic disorders that cause death in infants.

Types of atrophy

SMA can be divided into various types according to its manifestation which has been explained below:

  • Type I – This type of SMA is also known as Werdnig Hoffman disease. This happens to be a severe form of the genetic disorder which becomes evident during the time of birth or in the next few months of the baby. Babies affected with this type have delayed progress and developments. Most of them are also unable to sit on their own or keep their head in control. Babies affected with the Werdnig Hoffman disease suffer from swallowing and breathing problems that often lead to gagging and choking.
  • Type II – This type of the disorder is observed by the weakness of skeletal muscles that generally develops in babies between 6 to 12 months of age. While babies suffering from this disorder can sit on their own without any support, but they may need assistance in getting up to a seating position. However, the babies will not be able to stand and walk without support in this type of SMA.
  • Type III – This type of SMA is called Kugelberg Welander disease. This type has milder symptoms and features that usually develop during the early childhood as well as adolescence. Children with this type of SMA are able to stand and walk without any support but it is regressive and thus eventually the patient would start having difficulty in climbing stairs or even walking. It has been seen that a lot of patients became bound to a wheelchair in the later part of their life.
  • Type IV – This type of SMA occurs at a mature age of 30 or more. The patient would primarily experience mild or moderate weakness of muscles. They may also suffer twitching, tremor in the muscles and mild problem in breathing. In this type, usually, the proximal muscles that are located near the spinal cord are affected.

So, the most important question that remains is about the diagnosis and treatment of this regressive genetic disorder. How do we treat this disorder and is it possible to cure it completely? The answer to all these questions is Nusinersen. This is the only drug that got approved in December 2016 for the treatment of Spinal Muscular Atrophy. However, a lot of other components are still in the clinical trials.

Why is Nusinersen important?

Marketed by SpinrazaTM, Nusinersen is the first drug to be approved for treating the disorder of SMA1. The drug is supposed to be administered directly in the CNS or central nervous system by the help of an intrathecal injection. This helps in delivering the drug to the lower back passing through a lumbar puncture in the CNS.

More about the drug

The drug is manufactured by Biogen and comes with a disease-modifying treatment. The clinical trials of this drug proved effective and showed considerable improvement in patients suffering from SMA type I, II and III. The drug helped in:

  • Attaining physical milestones that were not possible without a proper treatment
  • Retain physical milestones that were also not possible without this medical treatment
  • Increase in life expectancy considering the type and condition of the disorder

However, there were no clinical trials performed on the Type IV patients with SMA. Nusinersen was first permitted by the European Commission on June 1, 2017, to treat SMA. The drug is now being widely used in the UK to treat children with Type I SMA.

Administering the drug

The treatment schedule of Nusinersen is divided into two segments – loading and maintaining the dosage. The first part of the dosage is loading where the patient is administered four doses within first 60 days or two months. Then in the maintenance part, the patient is administered one dose after every four months.

Side effects

The clinical trials have seen some adverse effects of Nusinersen. Risk of kidney damage, as well as, bleeding has been observed. Thus the physician will perform a urine and blood test before the administration of a dose. Even in the maintenance phase, these pathological tests are essential before loading any dose. Other side effects that have been observed in the trials are:

  • Constipation
  • Infection in the respiratory tract
  • Headache
  • Backache
  • Post-lumbar puncture condition

Nevertheless, the drug has shown progressive results in curing spinal muscular atrophy in Type I SMA as well as Type II and III. The drug has also helped in improving the motor function significantly in infants.

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