Current developments in gene therapy for amyotrophic lateral sclerosis.

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a devastating adult neurodegenerative disorder characterized by motor neuron degeneration and death around 3 years from onset. So far, riluzole is the only treatment available, although it only offers a slight increase in survival. The complex etiology of ALS, with several genes able to trigger the disease, makes its study difficult. Areas covered: RNA-mediated or protein-mediated toxic gain-of-function leading to motor neuron degeneration appears to be likely common pathogenic mechanisms in ALS. Consequently, gene therapy technologies to reduce toxic RNA and/or proteins and to protect motor neurons by modulating gene expression are at the forefront of the field. Here, we review the most promising scientific advances, paying special attention to the successful treatments tested in animal models as well as analyzing relevant gene therapy clinical trials. Expert opinion: Despite broad advances in target gene identification in ALS and advances in gene therapy technologies, a successful gene therapy for ALS continues to elude researchers. Multiple hurdles encompassing technical, biological, economical and clinical challenges must be overcome before a therapy for patients becomes available. Optimism remains due to positive results obtained in several in vivo studies demonstrating significant disease amelioration in animal models of ALS

Efficacy and safety of single pill combination of amlodipine and valsartan in hypertensive Saudi patients

OBJECTIVE: A significant global health issue that affects 25.5% of Saudi people is hypertension (HTN). According to international recommendations, most HTN patients require more than one therapy to reach their blood pressure targets (BP). Therefore, it would be preferable to utilize two medications from distinct classes separately or in a predetermined combination. According to recent studies, a single-pill combination (SPC) may be more efficient. This study evaluated the safety and tolerability of Amlodipine/Valsartan (Aml/Val) SPC in Saudi hypertensive patients, as well as the effectiveness of the medication. PATIENTS AND METHODS: Observational research was done prospectively at the King Fahad Armed Forces Hospital in Jeddah, Saudi Arabia. The effectiveness of the treatment and the percentage of 159 hypertensive patients who achieved the target blood pressure values (140/90; 130/80 mmHg) among those with diabetes mellitus (DM), chronic kidney disease (CKD), other cardiovascular disorders, and responders were assessed from the beginning to the endpoint (week 23). RESULTS: According to the results, taking Aml/Val SPC significantly lowered all patients’ baseline systolic and diastolic blood pressure readings by -17.97 and 8.58 mmHg, respectively. 43.4% of patients successfully met their BP therapeutic objectives by bringing their blood pressure levels back to normal, including 51.4% of patients under 65, 39.3% of patients with chronic kidney disease, and 26.2% of diabetic patients. Aml/Val 10/160 mg significantly lowers SBP, more than Aml/Val 5/160 mg (-13.32% vs. -9.00%, p<0.050). Vertigo (6.30%), respiratory tract infections (4.0%), and ankle edema (2.50%) were the most frequent adverse events. CONCLUSIONS: Aml/Val SPC therapy effectively lowered BP and had few side effects while being well-tolerated in people with hypertension