To study the tolerance and safety of increasing doses of AL-721 in patients with persistent generalized lymphadenopathy (PGL) and symptomatic HIV infection, and to obtain preliminary information on the effectiveness of AL-721 against the human immunodeficiency virus (HIV) in HIV-infected persons with PGL and symptomatic HIV infection. Although zidovudine (AZT) prolongs life in certain AIDS patients, it is not a cure for AIDS and it also has toxic effects in many patients. Therefore, it is necessary to test other drugs in HIV-infected patients. AL-721 is a mixture of lipids (fats) extracted from egg yolks. Laboratory tests suggest that it might inhibit the infectivity of the HIV. AL-721 has been tried so far in a few patients for short periods of time and has been found to be well tolerated.

Start Date-

Sponsor / Collaborator

National Institute of Allergy & Infectious Diseases

100 Clinical Results associated with AL-721

100 Translational Medicine associated with AL-721

100 Patents (Medical) associated with AL-721

Literatures (Medical) associated with AL-721

01 May 1997·Mechanisms of Ageing and DevelopmentQ2 · MEDICINE

The effect of aging on the immune response: influence of phosphatidylcholine-containing lipid on IgD-receptor expression and antibody formation

Q2 · MEDICINE

Article

Author: G.Jeanette Thorbecke ; Susan R.S Gottesman ; Joanne Edington ; Christina D Swenson ; Bin Xue

It was reported previously that IgD-receptors (IgD-R) are expressed on both CD4+ and CD8+ human T cells and CD4+ murine T cells after exposure to oligomeric IgD, certain cytokines, or various pharmacological agents, as shown by rosetting with IgD-coated erythrocytes. Enhancement of antibody production is observed in mice after injection of oligomeric IgD and is mediated by these IgD-R+ T cells, while injection of monomeric IgD inhibits both IgD-R upregulation and augmentation of antibody responses induced by simultaneously injected oligomeric IgD. The effects of oligomeric IgD on IgD-R upregulation are lacking in aged mice. However, the oligomeric IgD induced enhanced antibody production can be transferred to aged mice with IgD-R+ T cells from young donors suggesting that the environment of the aged mouse supports the effector function of IgD-R+ T cells. We now report, in addition, that exposure to phosphatidylcholine (PC) and a PC-containing lipid mixture, AL721, is effective in causing IgD-R upregulation on T cells from both young and aged mice, and young humans. This effect can also be demonstrated in mice in vivo after administration of AL721. Moreover, this agent causes a two-fold enhancement of antibody production, as measured by PFC/spleen, to 4-hydroxy-5-iodo-3-nitrophenyl(acetyl)-Brucella abortus (NIP-BA) and NIP-horse red blood cells (RBC) in young and aged mice. There is no difference in the baseline membrane fluidity of lymphocytes from aged and young mice. Although PC causes an increase in membrane fluidity of lymphocytes from both young and old mice, and from humans, this effect on fluidity is not prevented by a protein kinase inhibitor, while PC's effect on IgD-R upregulation is prevented by the inhibitor. Moreover, no correlation was observed between IgD-R upregulation and membrane fluidity changes induced by AL721 administered in vivo. To evaluate the role of IgD-R induction in the augmentation of antibody production by phospholipids, the effect of monomeric IgD was investigated. The augmenting effect of AL721 on antibody production was prevented by a single injection of monomeric IgD at the time of antigen administration. We conclude that (1) PC-containing lipid mixtures are effective in enhancing antibody production in aged mice, (2) induction of IgD-R is responsible for the augmenting effects of AL721 on antibody production, and (3) monomeric IgD not only blocks the upregulation of IgD-R, as shown previously, but also the augmenting effect of previously upregulated IgD-R on T cells by preventing their interaction with surface IgD+ B cells.

01 Jan 1992·Archives of Gerontology and GeriatricsQ3 · MEDICINE

The effects of in vivo administration of active lipids (AL-721) on natural killer cell activity and mitogen responsiveness in old rats

Q3 · MEDICINE

Article

Author: N. Fabris ; C. Di Stefano ; M. Provinciali ; C. Pieri

The cytotoxic activity of natural killer (NK) cells under both basal and interferon (IFN)-induced conditions, as well as the proliferative response of lymphocytes to ConA in old rats treated in vivo with AL-721 have been analyzed. The low levels of basal NK cell activity present in spleen of old rats were completely recovered to the levels of NK cytotoxicity obtained in young rats in animals treated in vivo with AL-721. Similar results were obtained for in vitro IFN-boosting of NK cells, in so far as the reduced IFN-responsiveness of NK cells from old untreated rats was restored to the levels of IFN-induced young NK activity in animals treated in vivo with AL-721. The evaluation of the proliferative response of lymphocytes to ConA revealed that old rats treated in vivo with AL-721 showed an increased proliferative capacity in comparison to old untreated animals even if the mitogenic response was not recovered up to the levels observed in young rats.

30 Sep 1991·International Journal of CancerQ1 · MEDICINE

Increased ether lipid cytotoxicity by reducing membrane cholesterol content

Q1 · MEDICINE

Article

Author: Alessandro Noseda ; Mario Salmona ; Luisa Diomede ; Edward J. Modest ; Bianca Piovani

AbstractEther‐linked glycerophospholipids (ether lipids, EL) are selectively toxic and anti‐proliferative agents against cancer cells in vitro. The reason for such selectivity is not completely clear. Their mechanism of action is mediated through an interaction with the plasma membrane and the membrane lipid composition may modulate it. As a continuation of previous reports, we now present data showing that cholesterol concentration modulates EL toxicity in the K562, U937 and MOLT4 leukemic cell lines in vitro. Cells become sensitive to otherwise ineffective doses of EL when their cholesterol content is lowered. Cell cholesterol levels were reduced by exposure to an egg lipid mixture (neutral glycerides, phosphatidylcholine and phosphatidylethanolamine, AL721). The data contribute to an understanding of the EL mechanism of action on membranes and suggest that the cellular cholesterol concentration must be considered a major factor in modulating the cytotoxic effects of EL.

100 Deals associated with AL-721

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Lymphadenopathy	Phase 3	US	National Institute of Allergy & Infectious Diseases	31 Aug 2001
Cystic Fibrosis	Phase 3	FR	-	-
HIV Infections	Phase 3	US	Ethigen, Inc.	-
Uterine Cervical Cancer	Phase 3	-	-	-
HIV Infections	Phase 2	US	Ethigen, Inc.	-

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