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HIV may underlie ALS-like condition
Newsdesk HIV may underlie ALS-like condition HIV infection in seven patients led to an amyotrophic lateral sclerosis (ALS)-like condition that “improved or even completely resolved” with antiretroviral medication, report French and US researchers (Neurology 2001; 57: 995–1001; 1094–97). “The findings are exciting because if some cases of amyotrophic lateral sclerosis [which is mostly fatal] are caused by HIV, then they can be treated with HAART, which has been very effective in slowing or even stopping the HIV infection”, argues Burk Jubelt (SUNY Upstate Medical University, Syracuse, NY, USA). The findings also suggest that “we might find other viruses that cause ALS cases that might be treatable”, Jubelt told TLID. From 1987 to 2000, Antoine Moulignier (Adolphe de Rothschild Foundation, Paris, France) and coworkers retrospectively identified six patients with an ALS-like disorder among 1700 HIV-infected patients with neurological symptoms. In all cases patients had upper and lower
motor neuron disease (MND), but only one patient met the E1 Escorial diagnostic criteria for definite ALS disease. The other five were labelled as “probable or possible” ALS cases. After they had received antiretroviral therapy, two of them recovered completely from their MND, three improved, and one stabilised. Moulignier noted that five of the six patients had been seen before the introduction of the drug cocktail of multiple antiretroviral drugs. Since then, Moulignier says his team has not seen any HIV-infected patient with MND symptoms. In the accompanying case report, Daniel MacGowan (Beth Israel Medical Center, NY, USA) and colleagues demonstrated a significant reduction in both plasma and cerebrospinal fluid viral load of a 32year-old HIV-infected woman with ALS after she had received antiretroviral therapy. “This is a seminal case report because it is the first time that an MND has
completely responded to any therapy”, MacGowan told TLID. His team plans to do a randomised double-blind placebo-controlled trial to examine the effect of indinavir on ALS among HIV-negative individuals. Raymond Roos (University of Chicago, Illinois, USA) argues that the “true ALS is not caused by HIV since the cases presented were different from classic ALS—since they were subacute in onset, were usually associated with inflammation in the spinal fluid, and were probably associated with immunosuppression in the host”. He added that the improvement with antiretroviral medication was not surprising “since the ALS-like disease is presumably a result of the HIV infection or infection by an opportunistic agent.” Another possibility is that the antiHIV protease treatment is effective as an antiapoptotic agent, and, for this reason, has a place in the treatment of typical ALS, he added. Khabir Ahmad
Combined adjuvants—new hope for mucosal vaccines structures formed by mixing cholesterol, lipid, and Quil A, produced from the bark of the South American saponaria tree. Whereas CT
Allan MI Mowat
A new mucosally active vaccineadjuvant has been created by an Anglo-Swedish team (J Immunol 2001; 167: 3398–405). “Most of the infectious diseases which are still a problem in the world are infections of mucosal surfaces, like the lung, intestine, and genital tract. . . A vaccine that protects such tissues would have to produce an immune response. . . in those tissues”, says Mowat, coauthor of the study. The creation of artificial mucosally active vaccines has been precluded by a scarcity of adjuvants that enhance the host's immune response. “You don't get an immune response without an adjuvant. . . Most organisms which cause infections carry their own adjuvant and that is why our body responds so vigorously to infections”, says Mowat. The team sought to improve immunostimulating capacities by combining two different adjuvants: cholera toxin (CT) and lipophilic immune-stimulating complexes (ISCOMS), which are tridimensional
Electron micrograph of artifcial adjuvants
is better at inducing IgA and serumantibody responses, ISCOMS are better at inducing cytokine production and MHC class-I-restricted CD8+ T cell responses. ISCOMS also serve as carriers for adjuvant proteins. CT induces T-cell-dependent responses when given orally, but can be extremely toxic. To overcome this a fusion protein was constructed from CTA1, the ADP-ribosylation active
THE LANCET Infectious Diseases Vol 1 November 2001
fragment of CT, and DD, a fragment of protein A from Staphylococcus aureus, whose presence prevents CTA1 entering certain cells. An ovalbumin epitope was used as the antigen with the combined adjuvant in tests with mice, and proved to be highly immunogenic in nanogram doses by different routes. After parenteral and oral applications, systemic antibody responses were higher than those found when the antigen was used alone or with either adjuvant separately. Systemic T cell responses were higher after parenteral, intranasal, and oral applications. The adjuvants were not toxic by any route. Brian Kelsall (NIH, Maryland, USA) says: “While mucosal immune responses were not specifically addressed, high levels of systemic humoral and cellular responses may well be necessary for protection against infection by pathogens that enter the body across mucosal surfaces, such as HIV". Claudia Orellana
217
For personal use. Only reproduce with permission from The Lancet Publishing Group.
motor neuron disease (MND), but only one patient met the E1 Escorial diagnostic criteria for definite ALS disease. The other five were labelled as “probable or possible” ALS cases. After they had received antiretroviral therapy, two of them recovered completely from their MND, three improved, and one stabilised. Moulignier noted that five of the six patients had been seen before the introduction of the drug cocktail of multiple antiretroviral drugs. Since then, Moulignier says his team has not seen any HIV-infected patient with MND symptoms. In the accompanying case report, Daniel MacGowan (Beth Israel Medical Center, NY, USA) and colleagues demonstrated a significant reduction in both plasma and cerebrospinal fluid viral load of a 32year-old HIV-infected woman with ALS after she had received antiretroviral therapy. “This is a seminal case report because it is the first time that an MND has
completely responded to any therapy”, MacGowan told TLID. His team plans to do a randomised double-blind placebo-controlled trial to examine the effect of indinavir on ALS among HIV-negative individuals. Raymond Roos (University of Chicago, Illinois, USA) argues that the “true ALS is not caused by HIV since the cases presented were different from classic ALS—since they were subacute in onset, were usually associated with inflammation in the spinal fluid, and were probably associated with immunosuppression in the host”. He added that the improvement with antiretroviral medication was not surprising “since the ALS-like disease is presumably a result of the HIV infection or infection by an opportunistic agent.” Another possibility is that the antiHIV protease treatment is effective as an antiapoptotic agent, and, for this reason, has a place in the treatment of typical ALS, he added. Khabir Ahmad
Combined adjuvants—new hope for mucosal vaccines structures formed by mixing cholesterol, lipid, and Quil A, produced from the bark of the South American saponaria tree. Whereas CT
Allan MI Mowat
A new mucosally active vaccineadjuvant has been created by an Anglo-Swedish team (J Immunol 2001; 167: 3398–405). “Most of the infectious diseases which are still a problem in the world are infections of mucosal surfaces, like the lung, intestine, and genital tract. . . A vaccine that protects such tissues would have to produce an immune response. . . in those tissues”, says Mowat, coauthor of the study. The creation of artificial mucosally active vaccines has been precluded by a scarcity of adjuvants that enhance the host's immune response. “You don't get an immune response without an adjuvant. . . Most organisms which cause infections carry their own adjuvant and that is why our body responds so vigorously to infections”, says Mowat. The team sought to improve immunostimulating capacities by combining two different adjuvants: cholera toxin (CT) and lipophilic immune-stimulating complexes (ISCOMS), which are tridimensional
Electron micrograph of artifcial adjuvants
is better at inducing IgA and serumantibody responses, ISCOMS are better at inducing cytokine production and MHC class-I-restricted CD8+ T cell responses. ISCOMS also serve as carriers for adjuvant proteins. CT induces T-cell-dependent responses when given orally, but can be extremely toxic. To overcome this a fusion protein was constructed from CTA1, the ADP-ribosylation active
THE LANCET Infectious Diseases Vol 1 November 2001
fragment of CT, and DD, a fragment of protein A from Staphylococcus aureus, whose presence prevents CTA1 entering certain cells. An ovalbumin epitope was used as the antigen with the combined adjuvant in tests with mice, and proved to be highly immunogenic in nanogram doses by different routes. After parenteral and oral applications, systemic antibody responses were higher than those found when the antigen was used alone or with either adjuvant separately. Systemic T cell responses were higher after parenteral, intranasal, and oral applications. The adjuvants were not toxic by any route. Brian Kelsall (NIH, Maryland, USA) says: “While mucosal immune responses were not specifically addressed, high levels of systemic humoral and cellular responses may well be necessary for protection against infection by pathogens that enter the body across mucosal surfaces, such as HIV". Claudia Orellana
217
For personal use. Only reproduce with permission from The Lancet Publishing Group.