Displaying publications 41 - 50 of 50 in total

Abstract:
Sort:
  1. Agyei D, Ahmed I, Akram Z, Iqbal HM, Danquah MK
    Protein Pept Lett, 2017;24(2):94-101.
    PMID: 28017145 DOI: 10.2174/0929866523666161222150444
    Bioactive proteins and peptides are recognised as novel therapeutic molecules with varying biological properties for potential medical applications. Development of protein and peptidebased therapeutic products for human use is growing steadily as they continue to receive an increasing rate of approval by the United States Food and Drugs Administration (US FDA). In this short review, we describe the current status and methodologies involved in the synthesis of protein and peptide biopharmaceuticals with an emphasis on the drivers and restrains to their exploitation in the therapeutic products sector.
    Matched MeSH terms: Proteins/therapeutic use
  2. Zaman R, Islam RA, Ibnat N, Othman I, Zaini A, Lee CY, et al.
    J Control Release, 2019 05 10;301:176-189.
    PMID: 30849445 DOI: 10.1016/j.jconrel.2019.02.016
    Macromolecular protein and peptide therapeutics have been proven to be effective in treating critical human diseases precisely. Thanks to biotechnological advancement, a huge number of proteins and peptide therapeutics were made their way to pharmaceutical market in past few decades. However, one of the biggest challenges to be addressed for protein therapeutics during clinical application is their fast degradation in serum and quick elimination owing to enzymatic degradation, renal clearance, liver metabolism and immunogenicity, attributing to the short half-lives. Size and hydrophobicity of protein molecules make them prone to kidney filtration and liver metabolism. On the other hand, proteasomes responsible for protein destruction possess the capability of specifically recognizing almost all kinds of foreign proteins while avoiding any unwanted destruction of cellular components. At present almost all protein-based drug formulations available in market are administered intravenously (IV) or subcutaneously (SC) with high dosing at frequent interval, eventually creating dose-fluctuation-related complications and reducing patient compliance vastly. Therefore, artificially increasing the therapeutic half-life of a protein by attaching to it a molecule that increases the overall size (eg, PEG) or helps with receptor mediated recycling (eg, albumin), or manipulating amino acid chain in a way that makes it more prone towards aggregate formation, are some of the revolutionary approaches to avoid the fast degradation in vivo. Half-life extension technologies that are capable of dramatically enhancing half-lives of proteins in circulation (2-100 folds) and thus improving their overall pharmacokinetic (PK) parameters have been successfully applied on a wide range of protein therapeutics from hormones and enzymes, growth factor, clotting factor to interferon. The focus of the review is to assess the technological advancements made so far in enhancing circulatory half-lives and improving therapeutic potency of proteins.
    Matched MeSH terms: Proteins/therapeutic use
  3. Sim SS, Vyas CH, Gunatheesan R, Lott PW, Sun CZ, Teo KYC, et al.
    Eye (Lond), 2022 Jun;36(6):1142.
    PMID: 35001091 DOI: 10.1038/s41433-021-01874-7
    Matched MeSH terms: Recombinant Fusion Proteins/therapeutic use
  4. Cheah KJ, Cheah LJ
    Nutr J, 2023 Oct 23;22(1):52.
    PMID: 37872544 DOI: 10.1186/s12937-023-00880-7
    BACKGROUND: Protein supplements have been widely used among those who are struggling with sarcopenic obesity among older adults. However, despite their popularity, there is still a lack of concrete evidence on both the potential benefits and side effects of protein supplementation and exercise on sarcopenic obesity (SO).

    OBJECTIVE: Thus, we aimed to determine the impacts of protein supplementation and exercise in older adults with sarcopenic obesity.

    METHOD: A systematic database search was conducted for randomised controlled trials, quasi experimental study and pre-post study design addressing the effects of protein supplementation in improving sarcopenic obesity among older adults. This scoping review was conducted based on PRISMA-Scr guidelines across PubMed, Embase, Web of Science and Cochrane Library databases. To assess record eligibility, two independent reviewers performed a rigorous systematic screening process.

    RESULTS: Of the 1,811 citations identified, 7 papers met the inclusion criteria. Six studies were randomised controlled trials and one study was a pre-post test study design. The majority of studies discussed the use of both protein supplements and exercise training. The included studies prescribed protein intake ranging from 1.0 to 1.8 g/kg/BW/day for the intervention group, while the duration of exercise performed ranged from 2 to 3 times per week, with each session lasting for 1 hour. Whey protein supplementation has been shown to be effective in improving sarcopenic conditions and weight status in SO individuals. The combination of exercise training especially resistance training and the used of protein supplement provided additional benefits in terms of lean muscle mass as well as biomarkers. The study also revealed a lack of consistency in exercise design among interventions for sarcopenic obesity.

    CONCLUSION: Overall, it appears to be a promising option for SO individuals to improve their sarcopenic condition and weight status through the combination of resistance exercise and whey protein supplementation. However, it also highlights the need for caution when it comes to high amounts of protein intake prescription. Future research is warranted to investigate the optimal exercise design for this population, given the limited research conducted in this specific area.

    Matched MeSH terms: Whey Proteins/therapeutic use
  5. Begley CG
    Med J Malaysia, 1993 Mar;48(1):3-8.
    PMID: 7688062
    The Colony Stimulating Factors (CSFs) are a family of haemopoietic hormones that likely share a common ancestral origin and stimulate white blood cell development. They display unique but overlapping biological functions and stimulate the survival, proliferation, differentiation and functional activation of granulocytes and monocytes/macrophages and their precursor cells in vitro and in vivo. Each hormone has been purified and produced in active recombinant form. Recombinant G-CSF and GM-CSF are now being used around the world in a variety of clinical situations (e.g., in conjunction with chemotherapy and bone marrow transplantation) to promote the formation and function of these leukocytes. These molecules are among the first of a new generation of biological agents that will impact enormously on clinical medicine.
    Matched MeSH terms: Recombinant Proteins/therapeutic use
  6. Cappellini MD, Viprakasit V, Taher AT, Georgiev P, Kuo KHM, Coates T, et al.
    N Engl J Med, 2020 03 26;382(13):1219-1231.
    PMID: 32212518 DOI: 10.1056/NEJMoa1910182
    BACKGROUND: Patients with transfusion-dependent β-thalassemia need regular red-cell transfusions. Luspatercept, a recombinant fusion protein that binds to select transforming growth factor β superfamily ligands, may enhance erythroid maturation and reduce the transfusion burden (the total number of red-cell units transfused) in such patients.

    METHODS: In this randomized, double-blind, phase 3 trial, we assigned, in a 2:1 ratio, adults with transfusion-dependent β-thalassemia to receive best supportive care plus luspatercept (at a dose of 1.00 to 1.25 mg per kilogram of body weight) or placebo for at least 48 weeks. The primary end point was the percentage of patients who had a reduction in the transfusion burden of at least 33% from baseline during weeks 13 through 24 plus a reduction of at least 2 red-cell units over this 12-week interval. Other efficacy end points included reductions in the transfusion burden during any 12-week interval and results of iron studies.

    RESULTS: A total of 224 patients were assigned to the luspatercept group and 112 to the placebo group. Luspatercept or placebo was administered for a median of approximately 64 weeks in both groups. The percentage of patients who had a reduction in the transfusion burden of at least 33% from baseline during weeks 13 through 24 plus a reduction of at least 2 red-cell units over this 12-week interval was significantly greater in the luspatercept group than in the placebo group (21.4% vs. 4.5%, P<0.001). During any 12-week interval, the percentage of patients who had a reduction in transfusion burden of at least 33% was greater in the luspatercept group than in the placebo group (70.5% vs. 29.5%), as was the percentage of those who had a reduction of at least 50% (40.2% vs. 6.3%). The least-squares mean difference between the groups in serum ferritin levels at week 48 was -348 μg per liter (95% confidence interval, -517 to -179) in favor of luspatercept. Adverse events of transient bone pain, arthralgia, dizziness, hypertension, and hyperuricemia were more common with luspatercept than placebo.

    CONCLUSIONS: The percentage of patients with transfusion-dependent β-thalassemia who had a reduction in transfusion burden was significantly greater in the luspatercept group than in the placebo group, and few adverse events led to the discontinuation of treatment. (Funded by Celgene and Acceleron Pharma; BELIEVE ClinicalTrials.gov number, NCT02604433; EudraCT number, 2015-003224-31.).

    Matched MeSH terms: Recombinant Fusion Proteins/therapeutic use*
  7. Rumaseb A, Moraes Barros RR, Sá JM, Juliano JJ, William T, Braima KA, et al.
    Antimicrob Agents Chemother, 2023 Jul 18;67(7):e0161022.
    PMID: 37314336 DOI: 10.1128/aac.01610-22
    Increasing reports of resistance to a frontline malaria blood-stage treatment, chloroquine (CQ), raises concerns for the elimination of Plasmodium vivax. The absence of an effective molecular marker of CQ resistance in P. vivax greatly constrains surveillance of this emerging threat. A recent genetic cross between CQ sensitive (CQS) and CQ resistant (CQR) NIH-1993 strains of P. vivax linked a moderate CQR phenotype with two candidate markers in P. vivax CQ resistance transporter gene (pvcrt-o): MS334 and In9pvcrt. Longer TGAAGH motif lengths at MS334 were associated with CQ resistance, as were shorter motifs at the In9pvcrt locus. In this study, high-grade CQR clinical isolates of P. vivax from a low endemic setting in Malaysia were used to investigate the association between the MS334 and In9pvcrt variants and treatment efficacy. Among a total of 49 independent monoclonal P. vivax isolates assessed, high-quality MS334 and In9pvcrt sequences could be derived from 30 (61%) and 23 (47%), respectively. Five MS334 and six In9pvcrt alleles were observed, with allele frequencies ranging from 2 to 76% and 3 to 71%, respectively. None of the clinical isolates had the same variant as the NIH-1993 CQR strain, and none of the variants were associated with CQ treatment failure (all P > 0.05). Multi-locus genotypes (MLGs) at 9 neutral microsatellites revealed a predominant P. vivax strain (MLG6) accounting for 52% of Day 0 infections. The MLG6 strain comprised equal proportions of CQS and CQR infections. Our study reveals complexity in the genetic basis of CQ resistance in the Malaysian P. vivax pre-elimination setting and suggests that the proposed pvcrt-o MS334 and In9pvcrt markers are not reliable markers of CQ treatment efficacy in this setting. Further studies are needed in other endemic settings, applying hypothesis-free genome-wide approaches, and functional approaches to understand the biological impact of the TGAAGH repeats linked to CQ response in a cross are warranted to comprehend and track CQR P. vivax.
    Matched MeSH terms: Protozoan Proteins/therapeutic use
  8. Tan SS, Adlin Nadia Z
    Med J Malaysia, 2017 06;72(3):165-174.
    PMID: 28733564 MyJurnal
    AIM: To describe the clinical characteristic of hepatitis C (HCV) patients and the results of pegylated interferon and ribavirin (PegIFN/RBV) therapy in a routine clinical practice.

    METHODS: A retrospective review of consecutive HCV patients treated with PegIFN/RBV in 2004 to 2012.

    RESULTS: A total of 273 patients received treatment. The mean age was 44.16 ± 10.5 years and 76% were male. The top 2 self-reported risks were blood or blood product transfusion before 1994 and injection drug use, found in 57.1% of patients. The predominant HCV genotype (GT) was 3 at 60.6%, second was GT1 at 36.1% and other GTs were uncommon at about 1% or less. About half of our patients have high baseline viral load (>800,000 iu/ml), 18.3% had liver cirrhosis and 22.3% had HIV co-infection. Co-morbid illness was found in 42.9%, hypertension and type 2 diabetes were the two most common. The overall sustained virological response (SVR) by intention-to-treat analysis were 54.9% (n=150/273), 41.2% (40/97) for GT1, 100% (5/5) for GT2 and 62% (101/163) for GT3. Subgroup analysis for HCV monoinfected, treatment naïve showed SVR of 49.2% (31/63) for GT1, 100% (5/5) for GT2 and 67% (69/103) for GT3. In HCV mono-infected and treatment experienced (n=29), the SVR was 28.6% (4/14) for GT1, 21.4% (69/103) for GT3. In the HIV/HCV co-infected, treatment naïve (n=56), the SVR was 28.6% (4/14) for GT1 and 64.3% (27/42) for GT3. Treatment naïve GT3 mono-infected patients had a statistically significant higher SVR compared to treatment experienced patients (P=0.001). In GT3 patients who achieved rapid virological response, the SVR was significantly higher at 85.2% (P< 0.001). The SVR for cirrhotics were low especially for GT1 at 21% (4/19) and 31% (4/13) based on all patients and treatment naïve HCV monoinfected respectively. In GT3 cirrhotics the corresponding SVR were 57.1% (16/28) and 60.9% (14/23). Premature discontinuation rate was 21.2% with the majority due to intolerable adverse events at 12.1%.

    CONCLUSIONS: In our routine clinical practice, the HCV patients we treated were young, predominantly of GT3 and many had difficult-to-treat clinical characteristics. The SVR of our patients were below those reported in Asian clinical trials but in keeping with some "real world" data.

    Matched MeSH terms: Recombinant Proteins/therapeutic use
  9. Ng BH, Mohd Aminudin NH, Nasaruddin MZ, Abdul Rahaman JA
    BMJ Case Rep, 2021 Feb 05;14(2).
    PMID: 33547099 DOI: 10.1136/bcr-2020-239702
    Patients with symptomatic complex malignant pleural effusion (MPE) are frequently unfit for decortication and have a poorer prognosis. Septations can develop in MPE, which may lead to failure of complete drainage and pleural infection. Intrapleural fibrinolytic therapy (IPFT) is an alternative treatment. The use of IPFT in patients with anaemia and high risk for intrapleural bleeding is not well established. We report a successful drainage of complex haemoserous MPE with a single modified low-dose of intrapleural 5 mg of alteplase and 5 mg of dornase alfa in a patient with pre-existing anaemia with no significant risk of intrapleural bleeding.
    Matched MeSH terms: Recombinant Proteins/therapeutic use
  10. Mahlangu J, Kuliczkowski K, Karim FA, Stasyshyn O, Kosinova MV, Lepatan LM, et al.
    Blood, 2016 Aug 04;128(5):630-7.
    PMID: 27330001 DOI: 10.1182/blood-2016-01-687434
    Recombinant VIII (rVIII)-SingleChain is a novel B-domain-truncated recombinant factor VIII (rFVIII), comprised of covalently bonded factor VIII (FVIII) heavy and light chains. It was designed to have a higher binding affinity for von Willebrand factor (VWF). This phase 1/3 study investigated the efficacy and safety of rVIII-SingleChain in the treatment of bleeding episodes, routine prophylaxis, and surgical prophylaxis. Participants were ≥12 years of age, with severe hemophilia A (endogenous FVIII <1%). The participants were allocated by the investigator to receive rVIII-SingleChain in either an on-demand or prophylaxis regimen. Of the 175 patients meeting study eligibility criteria, 173 were treated with rVIII-SingleChain, prophylactically (N = 146) or on-demand (N = 27). The total cumulative exposure was 14 306 exposure days (EDs), with 120 participants reaching ≥50 EDs and 52 participants having ≥100 EDs. Hemostatic efficacy was rated by the investigator as excellent or good in 93.8% of the 835 bleeds treated and assessed. Across all prophylaxis regimens, the median annualized spontaneous bleeding rate was 0.00 (Q1, Q3: 0.0, 2.4) and the median overall annualized bleeding rate (ABR) was 1.14 (Q1, Q3: 0.0, 4.2). Surgical hemostasis was rated as excellent/good in 100% of major surgeries by the investigator. No participant developed FVIII inhibitors. In conclusion, rVIII-SingleChain is a novel rFVIII molecule showing excellent hemostatic efficacy in surgery and in the control of bleeding events, low ABR in patients on prophylaxis, and a favorable safety profile in this large clinical study. This trial was registered at www.clinicaltrials.gov as #NCT01486927.
    Matched MeSH terms: Recombinant Proteins/therapeutic use*
Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links