Delving into the Latest Updates on Alavita Pharmaceuticals, Inc. with Synapse

Overview

Renal ischemia/reperfusion injury (IRI) frequently complicates cardiac and aortic surgery and has prognostic significance. The translocation of phosphatidylserines (PS) to cell surfaces is an important pro-inflammatory signal for cell-stress after IRI. We hypothesized that shielding of exposed PS by the annexin A5 homodimer Diannexin protects against renal IRI. Mice (n =8 – 10) underwent 20 min bilateral clamping of the renal pedicle, followed by 3 or 8 days of reperfusion. Either 200 ug/kg Diannexin or vehicle was injected i.v. 20 min prior to ischemia. Renal injury peaked on day 3 post-op. When compared to vehicle, Diannexin treatment reduced the IRI-induced glucosuria, prevented the increase in urine flow, reduced the proximal tubule damage and reduced the expression and/or transcription of the renal injury markers Neutrophil Gelatinase Associated Lipocalin (NGAL) and Kidney Injury Molecule-1 (KIM-1; see table ). Reduced KIM-1 expression persisted on day 8 after Diannexin treatment [0.23±0.02 vs. 0.36±0.06; p<0.05]. To confirm PS as the target for Diannexin, mice (n=2– 6) underwent unilateral IRI of the hind limb. Upon reperfusion, 4.5 ug Tc-99m-Diannexin was injected i.v. . Diannexin targeted specifically to the ischemic limb when compared to the control limb [4.0±0.60 vs. 0.2±0.02 %ID/g; p<0.001]. Targeting could be reduced by a preceding injection of 500 ug unlabeled annexin A5 [1.5±0.3 vs. 0.7±0.2 %ID/g], suggesting that Diannexin targets to ischemic tissues via PS binding. This study indicates the importance of PS exposition in IRI. We conclude that Diannexin protects against renal IRI by binding to PS, making it a promising tool to prevent IRI in a clinical setting.

Table:effects of Diannexin on functional, histological and injury marker parameters after renal IRI

01 Oct 2009·Current Opinion in ImmunologyQ2 · MEDICINE

Genetic control of resistance to human malaria

Q2 · MEDICINE

Review

Author: Allison, Anthony C

The term 'innate resistance' covers mechanisms of resistance that operate early in the course of infections, preceding adaptive immune responses which exert effects after several days. The first example of genetically controlled innate resistance to human malaria was the demonstration in 1954 that sickle-cell heterozygotes have less severe Plasmodium falciparum infections than do children with normal adult hemoglobin. This observation has been repeatedly confirmed, most recently by independent studies of genome-wide associations in severe falciparum malaria, which have identified the HBB locus as the major signal of association. Other abnormal hemoglobins, glucose-6-phosphate dehydrogenase deficiency and pyruvate kinase deficiency also confer some degree of resistance against falciparum malaria. A second early example of inherited innate resistance to malaria was the finding that nonexpression of the Duffy antigen/chemokine receptor (DARC) on erythrocytes confers resistance to P. vivax. However, this parasite can enter nonhuman primate red cells independently of DARC, and in some human populations P. vivax has been observed in persons lacking DARC. Hence DARC is not the only receptor for P. vivax, but it is likely to be a major one for human transmission. Innate resistance to malaria is rapidly reinforced by adaptive immune responses, both cell-mediated and humoral. Among the factors influencing the efficacy of adaptive immune responses to malaria is the MHC complex constitution of hosts. This differs among populations, presumably because of variations in the structure of parasite antigens recognized by the immune systems of hosts.

01 Jan 2009·Public Health GenomicsQ4 · MEDICINE

Observational, Hypothesis-Driven and Genomics Research Strategies for Analyzing Inherited Differences in Responses to Infectious Diseases

Q4 · MEDICINE

Review

Author: Allison, A C

The first phase of research on genetic factors influencing susceptibility to infectious diseases was observational and descriptive. It began with the identification of children and adults with selective and non-selective immunodeficiencies. The types of infections to which these patients are susceptible provided evidence for the roles of T-cells, B-cells, leukocytes, and complement in controlling infectious diseases. Later the biochemical bases for these deficiencies were characterized. For example, an abnormal tyrosine kinase is associated with X-linked agammaglobulinemia, and lack of adenosine deaminase results in severe combined immunodeficiency. The second strategy for analyzing inherited resistance to disease was hypothesis-driven. Observations on the distribution of the sickle-cell gene suggested that heterozygotes might be resistant to <i>P. falciparum </i>malaria. That proposal has been confirmed repeatedly. Persons heterozygous for other hemoglobin mutations and those with glucose-6-phosphate dehydrogenase deficiency also have some degree of resistance to malaria. The third, modern phase of research on susceptibility to infectious diseases is genomic. This powerful approach facilitated characterization of the mutations responsible for most of the above-mentioned defects. Moreover, genomics strategies make analyses of susceptibility to infections possible even when these are under multifactorial genetic control, as exemplified by malaria. This is likely to be true for most infectious diseases, so the genomic approach is an important way forward.

100 Deals associated with Alavita Pharmaceuticals, Inc.

Login to view more data

100 Translational Medicine associated with Alavita Pharmaceuticals, Inc.

Login to view more data

Corporation Tree

Boost your research with our corporation tree data.

login

or

view full example data

Boost your research with our corporation tree data.

Pipeline

Pipeline Snapshot as of 18 Jun 2025

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

Other

1

Login to view more data