It has been suggested that the reduced neural drive during exercise may be a protective mechanism to prevent organ failure if the work was continued at the same intensity. The exact mechanisms of central fatigue are unknown, though there has been considerable interest in the role of serotonergic pathways. Neuromuscular fatigue
Nerves control the contraction of muscles by determining the number, sequence, and force of muscular contraction. When a nerve experiences synaptic fatigue it becomes unable to stimulate the muscle that it innervates. Most movements require a force far below what a muscle could potentially generate, and barring pathology, neuromuscular fatigue is seldom an issue.For extremely powerful contractions that are close to the upper limit of a muscles ability to generate force, neuromuscular fatigue can become a limiting factor in untrained individuals. In novice strength trainers, the muscles ability to generate force is most strongly limited by nerves ability to sustain a high-frequency signal. After an extended period of maximum contraction, the nerves signal reduces in frequency and the force generated by the contraction diminishes. There is no sensation of pain or discomfort, the muscle appears to simply stop listening and gradually cease to move, often lengthening. As there is insufficient stress on the muscles and tendons, there will often be no delayed onset muscle soreness following the workout. Part of the process of strength training is increasing the nerves ability to generate sustained, high frequency signals which allow a muscle to contract with their greatest force.
The binding of isatuximab to CD38 on multiple myeloma (MM) cells leads to a trigger to several mechanisms leading to direct apoptosis of target cancer cells. The triggered pathways are the caspase-dependent apoptotic and the lysosome-mediated cell death pathway in MM cells.It is used in a combination with dexamethasone and pomalidomide. The drug is thus to treat patients with multiple myeloma. Restrictions for the use of isatuximab is that the patients have to be adults who have at least received two previous treatments with lenalidomide and a proteasome inhibitor.Isatuximab is currently also being tested in a Phase II trial as a monotherapy against refractory/recurrent systemic light-chain amyloidosis. Efficacy and side effects
Efficacy
A Phase III study of patients with refractory and relapsed MM, who were resistant to lenalidomide and a proteasome inhibitor, and could not have received daratumumab, another anti-CD38 monoclonal antibody was published in 2019 (ICARIA-MM). The addition of isatuximab to pomalidomide and dexamethasone improved progression free survival to 11.5 months compared to 6.5 months, with an overall response rate of 63%. Side effects
Adverse reactions to isatuximab-irfc may include neutropenia, infusion-related reactions and/or secondary primary malignancies. Of these three the most commonly occurring ones are the infusion-related reactions. Examples of the most frequent symptoms of infusion-related reactions are dyspnea, cough, chills, and nausea, while the severest signs and symptoms included hypertension and dyspnea. Effects on animals
The activity of isatuximab has been researched in mouse tumor models. It has been proven that isatuximab leads to antitumor activity in MM cells.