RESUMEN
Amyotrophic lateral sclerosis (ALS) is a rare disease characterized by a progressive and irreversible degeneration of upper and lower motor neurons leading to death. In France, limited data exist describing the criteria used in clinical practice for diagnosis and follow-up, and how novel therapies may fit in. The objective of this Delphi panel was to obtain an overview of current French practices in ALS diagnosis, management, and follow-up by determining the scales and criteria used in clinical practice outside of clinical trials, as well as the place of a future treatment like AMX0035, acting on endoplasmic reticulum (ER) stress and mitochondrial dysfunction, in the current therapeutic strategies. A questionnaire was administered to 24 ALS healthcare providers practicing in ALS centers in France. Two rounds of remote voting were organized, before proposition of final consensus statements. Consensus was considered reached when at least 66% of the voters agreed. Consensus were obtained to define the new Gold Coast criteria as the ones used in clinical practice to establish the diagnosis of ALS, thus replacing the revised El Escorial criteria, considered too complex and now mainly used to characterize the patient populations to be included in clinical trials. The clinical factors considered to establish ALS diagnosis are mainly the demonstration of progression of the motor deficit and elimination of differential diagnoses. The ALSFRS-R scale is used in daily clinical practice to assess patient's functional impairment in terms of number of points lost, with the bulbar, respiratory, and fine motor subscores being the most important to evaluate independently. A critical medical need was identified regarding the provision of new therapeutic alternatives in ALS. The panel members would support the earliest management of patients. In this landscape, based on data from a very encouraging phase II (Centaur trial), AMX0035 represents a new tool of choice in current treatment strategies for all patients for whom experts are confident in the diagnosis of ALS, in combination with riluzole. These results will need to be confirmed by the ongoing phase III trial (Phoenix trial).
Asunto(s)
Esclerosis Amiotrófica Lateral , Humanos , Esclerosis Amiotrófica Lateral/diagnóstico , Esclerosis Amiotrófica Lateral/terapia , Riluzol/uso terapéutico , Neuronas Motoras , Diagnóstico DiferencialRESUMEN
Osteoarthritis (OA) is a degenerative disorder of the joint, principally occurring during aging, and characterized by a focal degradation of cartilage. It is the most prevalent rheumatic disease in industrialized countries and represents the second cause of disability in France. However, the etiology of OA remains unclear. There is only one cell type found in cartilage, chondrocyte, which is responsible for its repair and the synthesis of the elements of the extra-cellular matrix. A dysfunction of these cells results in an imbalance between repair and degradation in cartilage, leading to its destruction. Recently, a link between OA and metabolic syndrome (MetS) has been suggested, introducing a notion of metabolic OA, and a new vision of the disease. MetS is characterized by a cluster of factors (insulin resistance, hypertension, dyslipidemia, visceral obesity), although there is still no clear definition of it. During the 20th century, MetS dramatically increased with changes in population lifestyle, becoming a major health issue in industrialized countries. MetS concerns 10-30% of the worldwide population, but is prevalent in 59% of OA patients. Patients with both OA and MetS have more severe symptoms, occurring sooner than in the general population. Indeed, OA is generally a disease concerning the population over 65 years old, but with an associated MetS the target population is around 50 years old. In this review, we will focus on common factors in OA and MetS, such as hypertension, obesity, dyslipidemia, mitochondrial dysfunction and hyperglycemia, linking one disease to the other.