Spinal muscular atrophy—recent therapeutic advances for an old challenge

Abstract

In the past decade, improved understanding of spinal muscular atrophy (SMA) aetiopathogenesis has brought us to a historical turning point: we are at the verge of development of disease-modifying treatments for this hitherto incurable disease. The increasingly precise delineation of molecular targets within the survival of motor neuron (SMN) gene locus has led to the development of promising therapeutic strategies. These novel avenues in treatment for SMA include gene therapy, molecular therapy with antisense oligonucleotides, and small molecules that aim to increase expression of SMN protein. Stem cell studies of SMA have provided an in vitro model for SMA, and stem cell transplantation could be used as a complementary strategy with a potential to treat the symptomatic phases of the disease. Here, we provide an overview of established data and novel insights into SMA pathogenesis, including discussion of the crucial function of the SMN protein. Preclinical evidence and recent advances from ongoing clinical trials are thoroughly reviewed. The final remarks are dedicated to future clinical perspectives in this rapidly evolving field, with a broad discussion on the comparison between the outlined therapeutic approaches and the remaining open questions.

A preimplantation genetic testing of monogenic diseases. Description of clinical case

“…Болезнь выражается в постепенном развитии симметричных вялых параличей и атрофии поперечно-полосатой мускулатуры, качественном перерождении соответствую-щих мышц и снижением их электровозбуди-мости [4]. Наиболее распространенной фор-мой в этой группе заболеваний является СМА с аутосомно-рецессивным типом наследова-ния.…”

Mutational analysis of SMN gene in patients with spinal muscular atrophy and the correlation between mutation and the severity of clinical manifestations

“…По опубликованным научным данным, распространенность заболевания составляет 1 случай на 6-10 тысяч новорожденных [1,2]. Большинство СМА наследуются по аутосомно-рецессивному типу.…”

Feasibility of combined treatment for type III spinal muscular atrophy: a pilot study

“…In conformity with the results of a preclinical study, in order to maintain SMN gene phenotype in the patients who have two replications of SMN2 gene, it is necessary to promote 25% increase in concentration of full-length SMN protein. 4 At present, there are no medicines that could help to cure or stop SMA disease progress in the patients. Clinical studies of the medical drug (nusinersen) give great expectations for progress in treatment of SMA patients.…”

“…2,3 Currently, there are no methods of treatment for SMA that could change this disease course in the patients. 4 Maintenance therapy consists in correction of symptoms of this disease along with prevention of future complications. The most frequent measures in such patients include a supply of necessary consumption of nutrients, maintenance of breathing, physical exercising, and auxiliary aid, which could be performed at terminal stages of the disease.…”