Experience of long-term use of Nusinersen in the treatment of spinal muscular atrophy types II, III

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Spinal muscular atrophy (SMA) is a progressive neurodegenerative disease with autosomal recessive inheritance characterized by increasing degeneration of α-motoneurons in the anterior horns of the spinal cord with the development of flaccid paralysis and muscular atrophy. The disease occurs at an incidence of 1/7-10,000 newborns and is a leading cause of early infant mortality. SMA is caused by a mutation in the SMN1 (Survival Motor Neuron1) gene, which encodes the survival motor neuron protein SMN (survival motor neuron protein). This protein is expressed universally and is involved in pre-mRNA splicing, transportation of mature mRNA and axon growth. Introduction of Nusinersen into clinical practice for pathogenetic treatment of SMA allows to improve motor activity, life expectancy, and quality of life of children with this pathology. Nusinersen is an antisense oligonucleotide that provides targeted drug delivery to spinal cord a-motoneurons and limits its biodistribution. 

Purpose of work: To analyze clinical cases of patients with SMA types II, III, to evaluate the efficacy and safety of the drug Nusinersen in long-term (2-3 years) treatment.

Materials and methods: 3 clinical cases of patients with SMA types II, III aged 14, 11 and 7 years, confirmed by molecular genetic study, were analyzed. The drug was administered intrathecally in dosage according to the instructions. Two patients were treated for 2 years, 1 patient - for 3 years.

Results: Positive dynamics of motor functions was observed in all patients against the background of therapy. Two children significantly increased the volume of movements, began to raise their arms above the shoulder girdle level, fine motor skills improved, muscle strength increased from 2-3 to 4 points. In the third patient the tremor in hands decreased, it became easier to pedal the simulator. No side effects were noted in any of the observations. One child had a transient headache associated with lumbar puncture.

Conclusions: Pathogenetic use of Nusinersen allowed significant improvement of motor functions of patients with different types of SMA and, therefore, should be carried out at early stages of the disease diagnosis. Long-term follow-up data (2-3 years) showed no side effects in therapy.

About the authors

Kseniya Alexandrovna Frolkova

St. Petersburg State Pediatric Medical University

Email: k.barbara07117@gmail.com
ORCID iD: 0009-0001-5419-7377
SPIN-code: 5822-4190
Russian Federation, 194100, Russia, St. Petersburg, st. Litovskaya, 2

Elizaveta Sergeevna Shanina

St. Petersburg State Pediatric Medical University

Email: shaninaliza@mail.ru
ORCID iD: 0009-0001-7920-692X
SPIN-code: 7175-3473
Russian Federation, 194100, Russia, St. Petersburg, st. Litovskaya, 2

Zara Grigorievna Tadtayeva

St. Petersburg State Pediatric Medical University

Author for correspondence.
Email: tadtaeva2003@mail.ru
ORCID iD: 0000-0002-5809-1457

MD, Professor of the Department of Pharmacology with a course in Clinical Pharmacology and Pharmacoeconomics

Russian Federation, 194100, Russia, St. Petersburg, Litovskaya str., 2

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