OPEN ACCESS ARTICLE – Demonstration of Biological and Immunological Equivalence of a Generic Glatiramer Acetate – CNS & Neurological Disorders – Drug Targets

Journal: CNS & Neurological Disorders – Drug Targets

Author(s): Josephine D`Alessandro, Kevin Garofalo, Ganlin Zhao, Christopher Honan, Jay Duffner, Ishan Capila, Ian Fier, Ganesh Kaundinya, Daniel Kantor, Tanmoy Ganguly

Graphical Abstract:


Background: In April 2015, the US Food and Drug Administration approved the first generic glatiramer acetate, Glatopa® (M356), as fully substitutable for Copaxone® 20 mg/mL for relapsing forms of multiple sclerosis (MS). This approval was accomplished through an Abbreviated New Drug Application that demonstrated equivalence to Copaxone.

Method: This article will provide an overview of the methods used to establish the biological and immunological equivalence of the two glatiramer acetate products, including methods evaluating antigenpresenting cell (APC) biology, T-cell biology, and other immunomodulatory effects.

Results: In vitro and in vivo experiments from multiple redundant orthogonal assays within four biological processes (aggregate biology, APC biology, T-cell biology, and B-cell biology) modulated by glatiramer acetate in MS established the biological and immunological equivalence of Glatopa and Copaxone and are described. The following were observed when comparing Glatopa and Copaxone in these experiments: equivalent delays in symptom onset and reductions in “disease” intensity in experimental autoimmune encephalomyelitis; equivalent dose-dependent increases in Glatopa- and Copaxone- induced monokine-induced interferon-gamma release from THP-1 cells; a shift to a T helper 2 phenotype resulting in the secretion of interleukin (IL)-4 and downregulation of IL-17 release; no differences in immunogenicity and the presence of equivalent “immunofingerprints” between both versions of glatiramer acetate; and no stimulation of histamine release with either glatiramer acetate in basophilic leukemia 2H3 cell lines.
Conclusion: In summary, this comprehensive approach across different biological and immunological pathways modulated by glatiramer acetate consistently supported the biological and immunological equivalence of Glatopa and Copaxone.


Testimonial by Ali Ganji!

Ali Ganji

Contributed Article: “IL-27: Friend Or Foe in the Autoimmune Diseases

Article by Disease – “Brain Aging and Disorders of the Central Nervous System: Kynurenines and Drug Metabolism”

Article by Disease on “Metabolic Disorders”


Introduction: The kynurenine pathway includes several neuroactive compounds, including kynurenic acid, picolinic acid, 3-hydroxykynurenine and quinolinic acid. The enzymatic cascade of the kynurenine pathway is tightly connected with the immune system, and may provide a link between the immune system and neurotransmission.

Main Areas Covered: Alterations in this cascade are associated with neurodegenerative, neurocognitive, autoimmune and psychiatric disorders, such as Parkinson’s disease, Huntington’s disease, Alzheimer’s disease, multiple sclerosis, amyotrophic lateral sclerosis, migraine or schizophrenia.

Highlights: This review highlights the alterations in this metabolic pathway in the physiological aging process and in different disorders. A survey is also presented of therapeutic possibilities of influencing this metabolic route, which can be achieved through the use of synthetic kynurenic acid analogues, enzyme inhibitors or even nanotechnology.

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“Induction and Escalation Therapies in Multiple Sclerosis”

On World Multiple Sclerosis Day, here is an Open Access Article from the journal “Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry

Author(s): G. Fenu, L. Lorefice, F. Frau, G.C. Coghe, M.G. Marrosu and E Cocco

aiaaAbstract: Multiple sclerosis (MS) is a chronic demyelinating disease affecting the central nervous system. Pharmacological therapy of MS includes symptomatic drugs, treatment for relapses (corticosteroid and intravenous immunoglobulin) and disease modifying drugs (DMDs) defined as pharmacological agents that have an impact on relapse rate, disability accumulation and radiological outcomes. Two different therapeutic approaches are widely used in MS: escalation and induction therapy. Escalation therapy consists of an early start with first line DMDs (beta interferon, glatiramer acetate, teriflunomide, dimethyl fumarate) and if DMDs are ineffective or partially effective, switching to second line drugs (mitoxantrone, natalizumab, fingolimod). Induction therapy consists of the early use of immunosuppressant drugs followed by long-term maintenance treatment, generally with immunomodulatory agents.

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