Efficacy of nusinersen in type 1, 2 and 3 spinal muscular atrophy: Real world data from Hungarian patients.

INTRODUCTION: Spinal muscular atrophy (SMA) is an autosomal recessive disorder caused by a homozygous deletion of the survival motor neuron (SMN) 1 gene. Nusinersen is an antisense oligonucleotide enhancing the production of the SMN protein. It has received approval by the European Medicines Agency (EMA) in 2017, based on the clinical trials demonstrating the effectiveness of nusinersen in several types of SMA. In Hungary, the first patient received nusinersen treatment in April 2018. Our aim is to summarize our experience regarding the efficacy, safety and tolerability of nusinersen in our patients. METHODS: Data were collected retrospectively in all types of SMA patients (type 1-3) starting treatment with nusinersen in Hungary between April 2018 and December 2019. Motor functions were evaluated at baseline, at the fourth and all following injections. RESULTS: By 31st December 2019, nusinersen therapy was initiated in 54 patients at either of the two Hungarian treatment centres. Mean age of the patients at the start of the treatment was 6.3 years (±5,4 range 0.4-17.9). 13 patients are type 1 (mean 0.78 ± 0.27, range 0.4-1.5 yrs), 21 patients are type 2 (mean 4.5 ± 3.3, range 1.3-12 yrs), 23 patients are type 3 (mean 10.9 ± 5.2, range 2.9-17.9 yrs). Fourteen patients had severe scoliosis, four of them underwent spine stabilizing surgery. During the study period 340 injections were administered without any new safety concerns emerging. The data of 38 patients, who had completed the first six treatments, were included in the final statistical analysis. Motor function has improved in most of the children. By the 307th day visit, on average, a 14.9 (±5,1) point improvement was measured on the CHOP INTEND scale in type 1 patients (p = 0.016). All patients with type 1 SMA who performed the motor evaluation (7/10) have improved by more than four (7-21) points. Regarding type 2 patients, a 7.2 (range -2- 17) point increase from baseline (p < 0.001) on the Hammersmith Functional Motor Scale Expanded (HFMSE) and 4.3 (range: 2-9) point increase (p = 0.031) on the Revised Upper Limb Module (RULM) were found. The distance of the 6 min walk test also increased by 33.9 m on average (range -16 - 106), in type 3 patients. CONCLUSION: According to our results nusinersen has the same safety and tolerability profile as in the clinical trials. In a heterogenic patient population of SMA type 1 and 2, nusinersen showed similar efficacy as seen in the pivotal studies. A clinically and statistically significant improvement of motor functions was also detectable in type 3 patients with heterogeneous age distribution.

Antioxidant value and element content in some tinctures used in medication.

Tinctures are almost the oldest medicines and their use is substantial in the medication nowadays as well. The antioxidant values by ferric reducing/antioxidant power (FRAP) method and element content by inductively coupled plasma optical emission spectrometry (ICP-OES) were investigated in some tinctures official in the VII. and VIII. Pharmacopoeia Hungarica. The highest FRAP values were found for volatile oil containing Tinctura Aurantii amari epicarpii et mesocarpii, Tinctura Amara and Tinctura Valerianae (764.54 ± 19.90; 757.37 ± 14.46; 826.40 ± 5.89 µmol l⁻¹, respectively). The correlations between the FRAP values and dilution with different alcohol content in Tinctura Chinae, Tinctura Ipecacuanhae normata and Tinctura Strychni were also investigated. Remarkable differences were found between the element concentrations in the different tinctures. The element contents in tinctures are not so high in absolute values nevertheless the presence of essential selenium, zinc, manganese and copper is important since they have key role in the antioxidant system. The common feature of the tinctures seems to be the lithium content. The Ca to Mg concentration ratio was found to be shifted towards magnesium in some of the tinctures that can show a higher Mg absorption which could affect against the proinflammatoric processes in the cases of gastrointestinal diseases.