Avalglucosidase alfa, sold under the brand name Nexviazyme, is an enzyme replacement therapy medication used for the treatment of glycogen storage disease type II (Pompe disease).The most common side effects include headache, fatigue, diarrhea, nausea, joint pain (arthralgia), dizziness, muscle pain (myalgia), itching (pruritus), vomiting, difficulty breathing (dyspnea), skin redness (erythema), feeling of "pins and needles" (paresthesia) and skin welts (urticaria).People with Pompe disease have an enzyme deficiency that leads to the accumulation of a complex sugar, called glycogen, in skeletal and heart muscles, which causes muscle weakness and premature death from respiratory or heart failure.Avalglucosidase alfa was approved for medical use in the United States in August 2021, and in the European Union in June 2022. Medical uses
Avalglucosidase alfa is indicated for the treatment of people aged one year and older with late-onset Pompe disease (lysosomal acid alpha-glucosidase [GAA] deficiency). Mechanism of action
Avalglucosidase alfa is composed of the human GAA enzyme that is conjugated with a couple of bis-mannose-6-phosphate (bis-M6P) tetra-mannose glycans. The bis-MGP of avalglucosidase alpha binds to the cation-independent mannose-6-phosphate receptor which is located on the skeletal muscles. Once the molecule binds to the receptor, the drug enters the cell. The drug then enters the lysosomes of the cell. Within the lysosome of the cell, the drugs undergoes cleavage proteolytically and then acts as an enzyme. Pharmacokinetics
The volume of distribution of avalglucosidase alfa was 3.4 L in patients who had Pompe disease of a late onset.
Children with DMDD are more at risk for developing major depressive disorder or generalized anxiety disorder when theyre older rather than bipolar disorder. Conduct Disorder
Conduct disorder is a behavior disorder characterized by repeated, persistent patterns of behavior that violate the rights of others and disregard major societal norms and rules. While both DMDD and conduct disorder are associated with argumentative and defiant behavior, DMDD is distinctly differentiated from conduct disorder by the DSM. Individuals with DMDD experience severe emotional dysregulation not seen in conduct disorder. Additionally, conduct disorder is described by a distinct lack of remorse and repeated physical harm and threats of harm to people and/or animals. Evidence of conduct disorder during childhood is one of the criteria for an adult diagnosis of antisocial personality disorder, however adults with a continued diagnosis of conduct disorder do not necessarily have antisocial personality disorder. Causes
Youth with DMDD have difficulty attending, processing, and responding to negative emotional stimuli and social experiences in their everyday lives. For example, some studies have shown youths with DMDD to have problems interpreting the social cues and emotional expressions of others. These youths may be especially bad at judging others negative emotional displays, such as feelings of sadness, fearfulness, and anger. Functional MRI studies suggest that under-activity of the amygdala, the brain area that plays a role in the interpretation and expression of emotions and novel stimuli, is associated with these deficits. Deficits in interpreting social cues may predispose children to instances of anger and aggression in social settings with little provocation.