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M Friede

Publications and source records attributed to M Friede.

12 recordsLinked to original sources
PubMed2006

Malaria vaccine development: progress and challenges.

A safe and effective malaria vaccine would contribute greatly to the control and prevention of the disease. Although a review of global activity in malaria vaccine development does reflect significant activity, progress has remained slow. This article discusses the current vaccine candidates, with emphasis on those in the clinic, and explains the numerous challenges to making and evaluating malaria vaccines, which have resulted in only a few approaches being adopted and repeatedly evaluated. Against a parasite with more than 5200 genes, the lack of definitive knowledge regarding the nature of protective immunity and absence of reliable surrogates of protection are among the key challenges to a rational evaluation and prioritization of candidate vaccines. Pursuing the current R&D strategies may not result in the availability of a vaccine with characteristics suitable to impact significantly on disease morbidity in developing countries. Therefore, it is critical that the main challenges to malaria vaccine development be unambiguously identified and collectively addressed.

Humans↗
PubMed2005

Efficacy and safety of 6.25 mg t.i.d. feverfew CO2-extract (MIG-99) in migraine prevention--a randomized, double-blind, multicentre, placebo-controlled study.

The efficacy and tolerability of a CO(2)-extract of feverfew (MIG-99, 6.25 mg t.i.d.) for migraine prevention were investigated in a randomized, double-blind, placebo-controlled, multicentre, parallel-group study. Patients (N = 170 intention-to-treat; MIG-99, N = 89; placebo, N = 81) suffering from migraine according to International Headache Society criteria were treated for 16 weeks after a 4-week baseline period. The primary endpoint was the average number of migraine attacks per 28 days during the treatment months 2 and 3 compared with baseline. Safety parameters included adverse events, laboratory parameters, vital signs and physical examination. The migraine frequency decreased from 4.76 by 1.9 attacks per month in the MIG-99 group and by 1.3 attacks in the placebo group (P = 0.0456). Logistic regression of responder rates showed an odds ratio of 3.4 in favour of MIG-99 (P = 0.0049). Adverse events possibly related to study medication were 9/107 (8.4%) with MIG-99 and 11/108 (10.2%) with placebo (P = 0.654). MIG-99 is effective and shows a favourable benefit-risk ratio.

Adolescent↗
PubMed2002

The efficacy and safety of Tanacetum parthenium (feverfew) in migraine prophylaxis--a double-blind, multicentre, randomized placebo-controlled dose-response study.

Tanacetum parthenium (feverfew), is a well-known herb for the prophylactic treatment of migraine. The primary objective was to show a dose-response of a new stable extract (MIG-99) reproducibly manufactured with supercritical CO2 from feverfew (T. parthenium). Furthermore, the study should provide data on the safety and tolerability of MIG-99. In a randomized, double-blind, multicentre, controlled trial with an adaptive design, the clinical efficacy and safety of three dosages of MIG-99 (2.08 mg; 6.25 mg; 18.75 mg t.i.d.) were compared with placebo. The patients (n = 147) suffered from migraine with and without aura according to International Headache Society (IHS) criteria and were treated with one of the study medications for 12 weeks after a 4-week baseline period. The primary efficacy parameter was the number of migraine attacks during the last 28 days of the treatment period compared with baseline. Secondary endpoints were total and average duration and intensity of migraine attacks, mean duration of the single attack, number of days with accompanying migraine symptoms, number of days with inability to work due to migraine as well as type and amount of additionally taken medications for the treatment of migraine attacks. The design of the study included a pre-planned adaptive interim analysis for patients with at least four migraine attacks within the baseline period. With respect to the primary and secondary efficacy parameter, a statistically significant difference was not found between the overall and the confirmatory intention-to-treat (ITT) sample in the exploratorily analysed four treatment groups. The frequency of migraine attacks for the predefined confirmatory subgroup of patients (n = 49) with at least four migraine attacks during the baseline period decreased in a dose-dependent manner (P = 0.001). The highest absolute change of migraine attacks was observed under treatment with 6.25 mg t.i.d. (mean +/- SD = -1.8 +/- 1.5 per 28 days) compared with placebo (-0.3 +/- 1.9; P = 0.02). Overall, 52 of 147 (35%) patients reported at least one adverse event (AE). The incidence of AEs in the active treatment groups was similar to that in the placebo group, and no dose-related effect was observed in any safety parameter. MIG-99 failed to show a significant migraine prophylactic effect in general. Accordingly, in the ITT analysis a dose-response relationship could not be observed. MIG-99 was shown to be effective only in a small predefined subgroup of patients with at least four attacks during the 28-day baseline period where the most favourable benefit-risk ratio was observed with a dosage of three capsules of 6.25 mg MIG-99 extract per day. Because of the low number of patients, these findings need to be verified in a larger sample. The incidence of AEs was similar for all treatment groups.

Adolescent↗
PubMed2001

Differential therapy of mild to moderate depressive episodes (ICD-10 F 32.0; F 32.1) with St. John's wort.

The purpose of this report was to evaluate specific depressive symptoms that are most suitable for a therapy with the Ze 117 St. John's wort extract. We examined the antidepressant efficacy and drug safety of Ze 117 and fluoxetine in a multicentric prospective randomized double-blind parallel group comparison according to generally accepted guidelines such as the Declaration of Helsinki and GCP. We treated outpatients (n = 240; Ze 117: 126; fluoxetine: 114) with mild to moderate depressive episodes (ICD-10: F 32.0, F 32.1; HAMD range: 16-24) with either two tablets St John's wort (Ze 117; 500 mg extract/day) or fluoxetine (20 mg/day) for 6 weeks. Antidepressant efficacy was evaluated with the validated HAMD psychometric method. A validated analysis of HAMD subscores was made to verify the efficacy for certain depressive symptoms. The main results were: * The HAMD responder rate was 60% in the Ze 117 group compared to 40% in the fluoxetine group (p = 0.005). * Particularly, there was a marked decrease of depressive agitation (pre-post comparison: 46%) and anxiety symptoms (44%) during the therapy with St. John's wort. Depressive obstruction (44%) and sleep disorders (43%) were reduced during the treatment, too. There were no statistically significant differences between the treatment groups. * Adverse events occurred in 28 patients (25%) in the fluoxetine group and in 18 (14%) of the St. John's wort group (p < 0.07). St. John's wort extract is a clinically effective equivalent to fluoxetine regarding overall depressive symptoms and main symptoms of depressive episodes. An especially interesting overall observation is that Ze 117 is particularly effective in depressive patients suffering from anxiety symptoms. St. John's wort revealed better safety and tolerability data than fluoxetine.

Adult↗
PubMed1994

Selective induction of protection against influenza virus infection in mice by a lipid-peptide conjugate delivered in liposomes.

We have previously reported (Muller et al. Vaccine 1990, 8, 308) that two cyclic peptide analogues called D loop and K loop, corresponding to residues 139-147 in site A of the haemagglutinin (HA) of influenza A virus (strain X31), were both able to provide protective immunity to infected OF1 mice when administered in the form of peptide-ovalbumin conjugates. The predicted conformation of the D loop is nearly identical to that of the native loop known from the X-ray structure of HA, while the predicted conformation of the K loop differs significantly from the native one. In this study, the two peptides were conjugated to small unilamellar liposomes, thus creating a chemically defined immunogen, and OF1 mice were immunized with these liposomes containing monophosphoryl lipid A as adjuvant. Compared with protein carrier systems, the liposomal preparations are completely synthetic and avoid the use of Freund's adjuvant. By using liposomes associated with the D loop, we were able to achieve 70% protection of the mice against intranasal challenge with the influenza virus while no protection was obtained with the liposome-associated K loop. The difference in effect between the two liposome and ovalbumin carrier systems may result from the induction of different structures in the peptides when coupled to lipid anchors than when coupled to proteins.

Administration, Intranasal↗
PubMed1993

Antigenicity and immunogenicity of modified synthetic peptides containing D-amino acid residues. Antibodies to a D-enantiomer do recognize the parent L-hexapeptide and reciprocally.

The effect of introducing D-amino acid residues in an hexapeptide was examined both at the antigenic and immunogenic levels. A series of D-analogues of the model peptide of sequence IRGERA corresponding to the COOH-terminal residues 130-135 of histone H3 were produced. Four analogues contained a single change of an L-residue by the corresponding enantiomer, one peptide contained two D-residues and another one contained only D-residues (D-enantiomer). A peptide analogue was also synthesized in which the 2 Arg residues were replaced by Lys residues. The parent peptide and peptide analogues were injected into mice after covalent coupling to small unilamellar liposomes containing monophosphoryl lipid A as adjuvant. The substitution of L-Arg131 to Lys or D-Arg was found to change neither the antigenic nor immunogenic properties of the resulting peptides. In contrast, the substitution of Glu133, Arg134, and Ala135 by the respective enantiomers drastically altered the antigenicity of the modified peptides. Each of the six D-analogues induced an immune response with an unusually high level of IgG3 antibodies. The D-enantiomer produced IgG3 antibodies which reacted with the homologous peptide as well as with the all L-peptide and the parent protein H3 in solution but not with analogues containing one or two D-residues only. IgG3 antibodies produced against the all L-peptide reacted with the free all D-peptide but not with the other analogues containing D-residues in position 133, 134, and 135.

Amino Acid Sequence↗
PubMed1993

Lyophilized liposomes as shelf items for the preparation of immunogenic liposome-peptide conjugates.

The conjugation of peptides to liposomes, while relatively simple, does represent a technical hurdle to some laboratories wishing to use such liposomes as vehicles to render peptides immunogenic. For such laboratories, having liposomes available as shelf items instead of having to prepare liposomes each time they are required may make liposomes more attractive. In this paper we report that small unilamellar liposomes bearing maleimide groups at their surface, and containing the adjuvant monophosphoryl lipid A, can be lyophilized and stored without loss of functionality or biological activity. On rehydration, peptides bearing cysteine residues are readily attached and the resulting conjugates exhibit the same immunogenicity as freshly prepared liposomes. These constructs avoid the use of protein carriers and also the use of Freund's adjuvant for raising antibodies against peptides.

Amino Acid Sequence↗
PubMed1993

Induction of immune response against a short synthetic peptide antigen coupled to small neutral liposomes containing monophosphoryl lipid A.

We have investigated the parameters affecting the immunogenicity of a short synthetic hexapeptide associated with liposomes. The model peptide used had the sequence IRGERA which corresponds to the C-terminal hexapeptide region of histone H3. Immunogenicity was measured by the ability of anti-peptide antibodies to cross-react with the parent protein. By itself, the peptide was not able to induce significant antibody production. However, liposomes were shown to be able to render the peptide immunogenic, nevertheless a number of parameters were important: to be immunogenic the peptide had to be surface bound, rather than entrapped within the liposomes, and an adjuvant, monophosphoryl lipid A (MPLA), had to be present in the same population of liposomes. Additionally, the intensity and duration of the immune response were found to be dependent both on the charge of the liposomes; neutral liposomes yielding a longer lasting response than negatively charged liposomes, and on the immunisation schedule where a long time period between immunisation and boosting yielded a better result than a short time period. To account for these phenomena we propose a model in which surface-bound antigen targets liposomal MPLA to B lymphocytes specific for the antigen. These results demonstrate that liposomes containing the non-toxic adjuvant MPLA can act as carriers to induce a long-lasting IgG response against peptides, eliminating the need of protein carriers and conventional adjuvants. Such an approach may be useful for designing synthetic vaccines.

Adjuvants, Immunologic↗
PubMedDate not supplied

Incomplete TFA deprotection of N-terminal trityl-asparagine residue in fmoc solid-phase peptide chemistry.

We demonstrate that TFA deprotection of trityl-protected N-terminal asparagine is incomplete under normal conditions, resulting in low yields or impure products. This phenomenon does not occur if the asparagine is internal, nor for trityl-protected N-terminal glutamine. Studies on the deprotection of H Asn(Trt)OH show that the incomplete deprotection is due to the extremely slow removal of a trityl group close to an amino group. The use of the new methyl-trityl protecting group overcomes this problem resulting in rapid and complete deprotection.

Amines↗
PubMedDate not supplied

Synthesis of arginine aldehydes for the preparation of pseudopeptides.

The synthesis of optically active aldehydes from N alpha-Boc-amino acids by reduction of the corresponding O,N-dimethyl-hydroxamates, while proceeding smoothly for most amino acids, has presented significant problems in the case of arginine. We demonstrate here that this difficulty can be overcome by the use of arginine derivatives in which the guanidino group is completely protected, such as in the case of N alpha-Boc-Arg(di-Z). In the case of nitro-, tosyl- or pmc-protected arginine, no satisfactory aldehyde formation can be obtained. It appears that in these cases the guanidino group is insufficiently protected and inhibits the formation of aldehydes. We also demonstrate that aldehydes can be readily obtained from N alpha-Fmoc protected amino acids.

Aldehydes↗