Review of eprodisate for the treatment of renal disease in AA amyloidosis

Rumjon, Adam; Coats, Thomas; Javaid, Muhammad Masoom

doi:10.2147/ijnrd.s19165

Cited by 10 publications

(3 citation statements)

References 52 publications

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“…To this end, high dose chemotherapy is used to non-specifically eliminate monoclonal plasma cells in patients with AL, and anti-inflammatory agents are employed to halt the production of the acute phase sAA protein. Other approaches include the use of small molecules to block protein-protein interactions [35], [36], orthotopic liver transplantation for patients with hereditary ATTR [37], and more recently, small interfering RNA techniques have been used to specifically target and reduce the production of amyloid precursor proteins [38]–[40].…”

Section: Discussionmentioning

confidence: 99%

AL Amyloid Imaging and Therapy with a Monoclonal Antibody to a Cryptic Epitope on Amyloid Fibrils

et al. 2012

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The monoclonal antibody 2A4 binds an epitope derived from a cleavage site of serum amyloid protein A (sAA) containing a -Glu-Asp- amino acid pairing. In addition to its reactivity with sAA amyloid deposits, the antibody was also found to bind amyloid fibrils composed of immunoglobulin light chains. The antibody binds to synthetic fibrils and human light chain (AL) amyloid extracts with high affinity even in the presence of soluble light chain proteins. Immunohistochemistry with biotinylated 2A4 demonstrated positive reaction with ALκ and ALλ human amyloid deposits in various organs. Surface plasmon resonance analyses using synthetic AL fibrils as a substrate revealed that 2A4 bound with a KD of ∼10 nM. Binding was inhibited in the presence of the –Glu-Asp- containing immunogen peptide. Radiolabeled 2A4 specifically localized with human AL amyloid extracts implanted in mice (amyloidomas) as evidenced by single photon emission (SPECT) imaging. Furthermore, co-localization of the radiolabeled mAb with amyloid was shown in biodistribution and micro-autoradiography studies. Treatment with 2A4 expedited regression of ALκ amyloidomas in mice, likely mediated by the action of macrophages and neutrophils, relative to animals that received a control antibody. These data indicate that the 2A4 mAb might be of interest for potential imaging and immunotherapy in patients with AL amyloidosis.

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Section: Discussionmentioning

confidence: 99%

AL Amyloid Imaging and Therapy with a Monoclonal Antibody to a Cryptic Epitope on Amyloid Fibrils

et al. 2012

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“…33–35 In addition, sulfonated molecules such as 3-amino-1-propanesulfonic acid and 1,3-propanedisulfonic acid have been shown to be effective inhibitors of A β and serum amyloid A aggregation, respectively. 36,37 …”

Section: Resultsmentioning

confidence: 99%

Peptide Conjugates of Benzene Carboxylic Acids as Agonists and Antagonists of Amylin Aggregation

2017

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Human islet amyloid polypeptide (hIAPP), also known as amylin, is a 37 residue peptide hormone that is stored and co-secreted with insulin. hIAPP plays a pivotal role in type 2 diabetes and is the major component of amyloid deposits found in the pancreas of patients afflicted with the disease. The self-assembly of hIAPP and the formation of amyloid is linked to the death of insulin producing β-cells. Recent findings suggest that soluble hIAPP oligomers are the cytotoxic species responsible for β-cell loss whereas amyloid fibrils themselves may indeed be innocuous. Potential avenues of therapeutic intervention include the development of compounds that prevent hIAPP self-assembly as well as those that reduce or eliminate lag time and rapidly accelerate the formation of amyloid fibrils. Both of these approaches minimize temporal exposure to soluble cytotoxic hIAPP oligomers. Toward this end our laboratory has pursued an electrostatic repulsion approach to the development of potential inhibitors and modulators of hIAPP self-assembly. Peptide conjugates were constructed in which benzene carboxylic acids of varying charge were employed as electrostatic disrupting elements and appended to the N-terminal of the hIAPP22–29 (NFGAILSS) self-recognition sequence. The self-assembly kinetics of conjugates were characterized by turbidity measurements and the structure of aggregates probed by Raman and CD spectroscopy while the morphology was assessed using transmission electron microscopy. Several benzene carboxylic acid peptide conjugates failed to self-assemble and some were found to inhibit the aggregation of full-length amylin while others served to enhance the rate of amyloid formation and/or increase the yield of amyloid produced. Studies reveal that the geometric display of free carboxylates on the benzene ring of the conjugates plays an important role in the activity of conjugates. In addition, a number of free benzene carboxylic acids were found to modulate amylin self-assembly on their own. The results of these investigations confirm the viability of the electrostatic repulsion approach to the modulation of amyloid formation and may aid the design and development of potential therapeutic agents.

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“…GAG mimetics such as 3-amino-1-propanesulfonic acid ( 3 ) 63 and eprodisate disodium ( 4 ) 64 have been tested as anti-amyloid agents for the treatment of Alzheimer’s disease and amyloidosis. Polysulfonated compounds such as suramin ( 5 ), 65 poly(sodium-4-styrene sulfonate) ( 6 ), 66 and sulfonate polymers have been tested as well.…”

Section: Targeting Heparan Sulfate-protein Interactionsmentioning

confidence: 99%

Targeting heparin and heparan sulfate protein interactions

2017

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Heparin and heparan sulfate glycosaminoglycans are long, linear polysaccharides that are made up of alternating dissacharide sequences of highly sulfated uronic acid and amino sugars. Unlike heparin, which is only found in mast cells, heparan sulfate is ubiquitously expressed on the cell surface and in the extracellular matrix of all animal cells. These negatively-charged carbohydrate chains play essential roles in important cellular functions such as cell growth, adhesion, angiogenesis, and blood coagulation. However, these biomolecules are also involved in pathophysiological conditions such as pathogen infection and human disease. This review discusses past and current methods for targeting these complex biomolecules as a novel therapeutic strategy to treating disorders such as cancer, neurodegenerative diseases, and infection.

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Review of eprodisate for the treatment of renal disease in AA amyloidosis

Cited by 10 publications

References 52 publications

AL Amyloid Imaging and Therapy with a Monoclonal Antibody to a Cryptic Epitope on Amyloid Fibrils

AL Amyloid Imaging and Therapy with a Monoclonal Antibody to a Cryptic Epitope on Amyloid Fibrils

Peptide Conjugates of Benzene Carboxylic Acids as Agonists and Antagonists of Amylin Aggregation

Targeting heparin and heparan sulfate protein interactions

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