Shenade Annie Kerketta, Amity University Kolkata
SPINAL MUSCULAR ATROPHY (SMA) is a rare genetic condition that affects the spinal cord. In individuals affected by SMA, the motor neurons are damaged. This kills the ability to crawl, walk, and control head movements. SMA affects infants younger than seven months. The symptoms include – limited mobility, breathing problems, scoliosis, and delayed gross motor skills. The disease is caused due to lack of SMN (survival of motor neurons). When mutations occur on chromosome five located in the gene SMN1, it leads to a lack of SMN. SMA is one of the most common reasons behind infant mortality. There is no cure developed up-till now and, neither can this disease be prevented. Therefore, research is extensively taking place and, advances have been made. The recent advancement is the development of a drug called RISDIPLAM.
The types of SMA
- TYPE 1: This is, termed as WERDNIG-HOFFMAN disease which affects 60% of the SMA population. Symptoms appear within the first six months of an infant. This is the most severe form which only allows two years of life.
- TYPE 2: This is also termed as DUBOWITZ disease. Here, the symptoms appear within the first 18 months of life. This type might be able to sit but cannot walk. Also, most children live up-till adulthood.
- TYPE 3: This is also termed as KUGELBERT WELANDER disease. Symptoms appear after a child’s first 18 months. This form is a mild one, which includes slight muscle weakness, respiratory infections, and difficulty in walking. This one does not threaten life expectancy much.
- TYPE 4: This is the rarest form that affects the adult SMA population. Symptoms appear after the mid-30s. This type allows individuals to live full lives where the muscle weakness progresses slowly.
RRISDIPLAM: How effective is it?
In a recent study published in the New England Journal of Medicine, it was shown that risdiplam is a fairly effective drug, when compared to previous discoveries and while keeping in mind that the disease has no cure. The study aimed to achieve unsupported sitting for five seconds. 41 infants were subject to this drug. The drug is a small molecule drug that is supposed to be consumed orally. Infants suffering from type 1 SMA were selected (type 1 SMA causes the most harm). After one year of treatment, 12 individuals could sit unsupported for some time. This is a milestone achieved.
Working mechanism: Risdiplam works by increasing the levels of SMN by increasing generation from the SMN2 gene.
Previous drug developments:
- SPINRAZA (nusinersen): This works by reversing the symptoms. The drug is introduced in the spinal canal by lumbar puncture. It is an antisense oligonucleotide that stimulates the SMN2 gene to produce more SMN. It has shown good results.
- ZOLGENSMA: It is a gene replacement therapy that delivers a good version of the SMN1 gene. 33 infants have been treated. It is a one-time infusion method.
RISDIPLAM and the future of SMA treatment
The new development of RISDIPLAM has shown great results and higher efficiency in improved motor function. Success in this field is progressing slowly, but effectively. Further experiments and research are a must so that we can find a proper cure. Newborn SMA screening has also come up where SMA in babies is detected earlier, thus ensuring more effective treatment. It has been found that the earlier that SMA is diagnosed, the better are the results of treatment.
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Reference:
Darras, B. T., Masson, R., Mazurkiewicz-Bełdzińska, M., Rose, K., Xiong, H., Zanoteli, E., Baranello, G., Bruno, C., Vlodavets, D., Wang, Y., El-Khairi, M., Gerber, M., Gorni, K., Khwaja, O., Kletzl, H., Scalco, R. S., Fontoura, P., & Servais, L. (2021). Risdiplam-treated infants with type 1 spinal muscular atrophy versus historical controls. New England Journal of Medicine, 385(5), 427–435. https://doi.org/10.1056/NEJMoa2102047
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