Late infantile form
The CLN2 gene encodes a 46kDa protein called lysosomal tripeptidyl peptidase I (TPP1), which cleaves tripeptides from terminal amine groups of partially unfolded proteins. Mutations of this gene typically result in a LINCL phenotype.On April 27, 2017, the U.S. Food and Drug Administration approved cerliponase alfa (Brineura) as the first specific treatment for NCL. It is enzyme replacement therapy manufactured through recombinant DNA technology. The active ingredient in Brineura, cerliponase alfa, is intended to slow loss of walking ability in symptomatic pediatric patients 3 years of age and older with late infantile neuronal ceroid lipofuscinosis type 2 (CLN2), also known as TPP1 deficiency. Brineura is administered into the cerebrospinal fluid by infusion via a surgically implanted reservoir and catheter in the head (intraventricular access device). Juvenile form
All mutations resulting in the juvenile variant of NCL have been shown to occur at the CLN3 gene on 16p12; of the mutations known to cause JNCL, 85% result from a 1.02-kb deletion, with a loss of amino acids 154–438, while the remaining 15% appear to result from either point or frameshift mutations. The wild-type CLN3 gene codes for a protein with no known function, but studies of the yeast CLN3 ortholog, the product of which is called battenin (after its apparent connections to Battens disease, or JNCL), have suggested that the protein may play a role in lysosomal pH homeostasis.
Mechanisms
Losartan works by blocking the effects of angiotensin II by preventing it from binding to the angiotensin I receptor while hydrochlorothiazide works by decreasing the ability of the kidneys to absorb electrolytes. The effects of hydrochlorothiazide indirectly lower the levels of serum potassium. However, with coadministration of losartan which is an angiotensin II receptor antagonist, the low levels of potassium are reversed. Brand names
The losartan/hydrochlorothiazide combination preparation is marketed by Merck under the brand name Hyzaar and by Xeno Pharmaceuticals under the name Anzaplus. Merck, Sharp & Dohme market it as Ocsaar Plus in Israel. It is marketed as Cozaar comp in Sweden and South Africa. References
External links
"Hydrochlorothiazide mixture with Losartan". Drug Information Portal. U.S. National Library of Medicine.