Expert opinion on investigational drugs
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Expert Opin Investig Drugs · Feb 2011
ReviewMipomersen, an antisense apolipoprotein B synthesis inhibitor.
mipomersen is a second-generation antisense oligonucleotide (ASO) targeted to human apolipoprotein (apo) B-100, a large protein synthesized by the liver that plays a fundamental role in human lipoprotein metabolism. Mipomersen predominantly distributes to the liver and decreases the production of apoB-100, the primary structural protein of the atherogenic lipoproteins including low density lipoprotein (LDL), thereby reducing plasma LDL-cholesterol and apoB-100 concentrations. ⋯ mipomersen shows promise as an adjunctive agent by reducing apoB-containing lipoproteins in patients at high risk of atherosclerotic cardiovascular disease who are not at target or are intolerant of statins. Although the short-term efficacy and safety of mipomersen has been established, concern exists regarding the long-term potential for hepatic steatosis with this ASO.
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Expert Opin Investig Drugs · Dec 2010
ReviewAfamelanotide, an agonistic analog of α-melanocyte-stimulating hormone, in dermal phototoxicity of erythropoietic protoporphyria.
Afamelanotide, an α-melanocyte stimulating hormone (MSH) agonistic analog is a first-in-class therapeutic. Its application to protoporphyria (PP), a disease associated with absolute sunlight-intolerance is discussed. ⋯ Although early, results of the first trials of afamelanotide for PP are promising and the risk-safety profile appears favorable today. We expect afamelanotide and analogs thereof to be a prospective therapeutic tool in light-related skin diseases, and in future this drug class might prove effectiveness in other medical conditions.
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Alcohol use and dependence are frequent disorders. Despite numerous established psychosocial approaches, relapse to heavy drinking is common in alcohol-dependent patients after detoxification and relapse prevention remains a significant medical challenge. ⋯ Although the number of clinical studies conducted with naltrexone by far exceeds the number conducted with nalmefene, the four studies on nalmefene published so far may indicate a role of this opioid antagonist in the treatment of alcoholism. Results of some ongoing studies on nalmefene will provide additional data on its use for this indication.
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Expert Opin Investig Drugs · Sep 2010
Randomized Controlled Trial Comparative StudyComparison between the antiproteinuric effects of the calcium channel blockers benidipine and cilnidipine in combination with angiotensin receptor blockers in hypertensive patients with chronic kidney disease.
Benidipine, an L-/T-type calcium channel blocker, dilates renal efferent and afferent arterioles and reduces glomerular pressure; therefore, it may exert renoprotective effects. We conducted an open-labeled randomized trial to compare the effects of benidipine with cilnidipine in hypertensive patients with chronic kidney disease (CKD). ⋯ The addition of benidipine as well as cilnidipine reduces urinary protein excretion in hypertensive patients with CKD who are already being administered ARBs.
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Expert Opin Investig Drugs · Sep 2010
ReviewNew small molecules for the treatment of Parkinson's disease.
Parkinson's disease (PD) is characterized by a slowly ongoing neuronal death, which affects neurotransmitter metabolism and causes a wide variety of motor and non-motor features. Until now, therapy approaches have predominantly focused on motor behavior associated with dopamine substitution. ⋯ In the past, research pitfalls have resulted in the failure of promising new compounds. Among the many reasons for this are massive placebo responses; the participation of too many investigators, with consequent wide variations of efficacy assessments; and a misconception of preclinical drug development, with models of PD that do not mimic its clinical nature. A few compounds are now being tested that have modes of action indirectly modulating the dopamine system; however, critical analysis of the preclinical and clinical research concept and drug approval is warranted to prevent further frustration in this field.