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- Hellström, Per M., 1954-, et al.
(author)
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Irritable Bowel syndrome : Principles and novel treatment options
- 2011
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In: Drugs of the future. - 0377-8282 .- 2013-0368. ; 36:9, s. 669-675
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Research review (peer-reviewed)abstract
- There is growing interest in the area of irritable bowel syndrome (IBS) in developing tools to separate various subgroups of this disease in order to identify potentially different pathogenetic mechanisms. From such work, the ultimate goal is tailored treatment for the various subtypes of the disease. Among major achievements in this research, the finding of increased gut permeability is of great interest and suggests a luminal factor as a cause of disease, which would be able to maintain low-grade inflammation. There are various treatment options and significant activity in developing drugs that have the capability to inhibit gut motility and increase luminal secretion. The development of analogues to gut peptide hormones, such as glucagon-like peptide 1, is of primary interest, as these drugs rarely give rise to inconvenient adverse reactions at therapeutic doses. Some of these drugs even exert their action directly on the luminal membranes, such as linaclotide, which means that oral administration is favored to diminish the risk of systemic reactions. The concept of IBS is anticipated to evolve into different disease mechanisms that will serve as the basis for customized treatments.
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- Hellström, Per
(author)
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ULIMORELIN Ghrelin (GHS) Receptor Agonist Treatment of Postoperative Ileus Treatment of Gastroparesis
- 2011
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In: Drugs of the future. - 0377-8282 .- 2013-0368. ; 36:12, s. 899-907
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Journal article (peer-reviewed)abstract
- Hunger contractions consist of a series of strong contractions of the stomach that evolve to phase Ill of the migrating motor complex and move down the small intestine. Ghrelin is considered to be important for the initiation of hunger contractions and promotes gastric emptying. Other gastrointestinal endocrine and neuronal systems play powerful supplementary roles in the development of hunger. Macrocyclic template chemistry (MATCH (TM)) has produced the macrocyclic peptidomimetic ulimorelin (TZP-101). By an action selectively directed to the ghrelin receptor, this peptide analogue has been shown to be able to stimulate gastric emptying in diabetic gastroparesis and relieve the associated symptom burden in gastroparesis, predominantly nausea and vomiting. Ulimorelin has also been shown to be effective in reducing postoperative ileus in colectomy. These effects are not associated with any serious adverse events. As ulimorelin opens up new indications for treatment, this will strengthen the possibility of relieving patients of symptoms related to stasis of contents in the upper gastrointestinal tract. Thus, ulimorelin is a promising pharmaceutical that should activate gastrointestinal regulatory systems in disorders associated with gastric hypomotility.
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- Pisanu, Claudia, et al.
(author)
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Rationale of the potential role of lithium in the antiaging arena
- 2020
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In: Drugs of the future. - : Clarivate Analytics (US). - 0377-8282 .- 2013-0368. ; 45:6, s. 397-407
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Research review (peer-reviewed)abstract
- Lithium is the mainstay treatment in the management of bipolar disorder. A growing body of findings suggests that lithium could be considered a neuroprotective agent that might slow the progression of neurobiological abnormalities in Alzheimer's disease and possibly in other neurodegenerative disorders. Additionally, the effect of lithium on telomere length, as well as the increased overall survival associated with microdoses of lithium in drinking water, led to hypothesize that lithium might have "antiaging" properties. In this review, we summarize available evidence from preclinical and clinical studies investigating the potential beneficial effects of lithium in the antiaging arena and in neurodegenerative disorders, as well as the putative underlying molecular mechanisms, including inhibition of the glycogen synthase kinase-3 (GSK-3) enzyme, reduction of oxidative stress and counteraction of telomere shortening. Additionally, we present a timely overview of currently active clinical trials that might enhance our understanding of the beneficial properties of lithium and highlight the potential for drug repurposing.
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- Suhr, Ole B, et al.
(author)
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Transthyretin amyloidoses : new strategies for therapeutic intervention
- 2010
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In: Drugs of the future. - : Clarivate Analytics (US). - 0377-8282 .- 2013-0368. ; 35:4, s. 325-332
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Journal article (peer-reviewed)abstract
- Liver transplantation as a treatment for transthyretin amyloidosis (ATTR) was introduced 20 years ago and is currently the only available treatment for the disease. Although the procedure has been proven to halt the progression of the disease for most patients, several unexpected complications have emerged, and it is obvious that for several mutations liver transplantation has no impact on the progression of the disease. Heart complications, especially in elderly patients, have been a cause of concern for many patients, including those with the most widespread neuropathic mutation, transthyretin (TTR)Val30Met. These drawbacks and the risk involved with transplantation, together with the need for life-long immunosuppressive therapy, have demonstrated the need for an effective medical treatment. From the experience with liver transplant patients, it appears that the amyloidogenic properties of wild-type TTR are enhanced once amyloid formation has started, and that elimination of the mutated TTR is not sufficient to prevent further amyloid formation in all cases. The development of animal models for the disease has further increased our understanding of factors involved in amyloid formation, and offers the possibility to test new medical treatment modalities. From our experience with liver transplantation, it appears that treatment directed towards stabilizing the TTR tetramer, eliminating misfolded TTR, decreasing TTR serum concentrations, decreasing toxicity and removing amyloid deposits are the most attractive modalities for treatment. Several studies are currently planned or ongoing to explore these possibilities, and promising results are already being reported.
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