Copolymer-1 as a potential therapy for mild cognitive impairment.

Mild cognitive impairment (MCI) is a prodromal stage of memory impairment that may precede dementia. MCI is classified by the presence or absence of memory impairment into amnestic or non-amnestic MCI, respectively. More than 90% of patients with amnestic MCI who progress towards dementia meet criteria for Alzheimer's disease (AD). A combination of mechanisms promotes MCI, including intracellular neurofibrillary tangle formation, extracellular amyloid deposition, oxidative stress, neuronal loss, synaptodegeneration, cholinergic dysfunction, cerebrovascular disease, and neuroinflammation. However, emerging evidence indicates that neuroinflammation plays an important role in the pathogenesis of cognitive impairment. Unfortunately, there are currently no Food and Drug Administration (FDA)-approved drugs for MCI. Copolymer-1 (Cop-1), also known as glatiramer acetate, is a synthetic polypeptide of four amino acids approved by the FDA for the treatment of relapsing-remitting multiple sclerosis. Cop-1 therapeutic effect is attributed to immunomodulation, promoting a switch from proinflammatory to anti-inflammatory phenotype. In addition to its anti-inflammatory properties, it stimulates brain-derived neurotrophic factor (BDNF) secretion, a neurotrophin involved in neurogenesis and the generation of hippocampal long-term potentials. Moreover, BDNF levels are significantly decreased in patients with cognitive impairment. Therefore, Cop-1 immunization might promote synaptic plasticity and memory consolidation by increasing BDNF production in patients with MCI.

Glatiramer Acetate Immunomodulation: Evidence of Neuroprotection and Cognitive Preservation.

Novel, neuroprotective uses of Copaxone (generic name: glatiramer acetate-GA) are being examined, primarily in neurological conditions involving cognitive decline. GA is a well-studied synthetic copolymer that is FDA-approved for immune-based treatment of relapsing remitting multiple sclerosis (RRMS). Clinical studies have explored the potential mechanism of action (MOA) and outcomes of GA immunization in patients. Furthermore, results from these and animal studies suggest that GA has a direct immunomodulatory effect on adaptive and innate immune cell phenotypes and responses. These MOAs have been postulated to have a common neuroprotective impact in several neuroinflammatory and neurodegenerative diseases. Notably, several clinical studies report that the use of GA mitigated MS-associated cognitive decline. Its propensity to ameliorate neuro-proinflammatory and degenerative processes ignites increased interest in potential alternate uses such as in age-related macular degeneration (AMD), amyotrophic lateral sclerosis (ALS), and Alzheimer's disease (AD). Preclinical studies are exploring less frequent subcutaneous administration of GA, such as once weekly or monthly or a single dosing regimen. Indeed, cognitive functions were found to be either preserved, reversed, or improved after the less frequent treatment regimens with GA in animal models of AD. In this systematic review, we examine the potential novel uses of GA across clinical and pre-clinical studies, with evidence for its beneficial impact on cognition. Future investigation in large-size, double-blind clinical trials is warranted to establish the impact of GA immunomodulation on neuroprotection and cognitive preservation in various neurological conditions.

Processability evaluation of multiparticulate units prepared by selective laser sintering using the SeDeM Expert System approach.

3D printing in dosage forms fabrication is in the focus of researchers, however, the attempts in multiparticulate units (MPUs) preparation are scarce. The aim of this study was to fabricate different size MPUs by selective laser sintering (SLS), using different polymers, and investigate their processability based on the SeDeM Expert System approach. MPUs (1- or 2-mm size) were prepared with model drug (ibuprofen or caffeine), polymer (poly(ethylene)oxide (PEO), ethyl cellulose (EC) or methacrylic acid-ethyl acrylate copolymer (MA-EA)) and printing aid. Comprehensive sample characterization was performed and experimentally obtained parameters were mathematically transformed and evaluated using the SeDeM Expert System framework. The obtained samples exhibited irregular shape, despite the spherical printing object design. Polymer incorporated notably affected MPUs properties. The obtained samples exhibited low bulk density, good flowability-, as well as stability-related parameters, which indicated their suitability for filling into capsules or sachets. Low density values implied that compressibility enhancing excipients may be required for MPUs incorporation in tablets. Samples containing EC and MA-EA were found suitable for compression, due to high compacts tensile strength. The obtained results indicate that SeDeM Expert System may extended from powder compressibility evaluation tool to framework facilitating powders/multiparticulate units processing.