På ME-fronten: Behandling med GcMAF – en intro

Stadig flere behandlere tilbyr GcMAF til sine pasienter og har blitt det en kan kalle en «hype». I utgangspunktet har GcMAF blitt brukt som tillegg til kreftbehandling og behandling av HIV-pasienter. I den senere tid har den blitt populær å bruke på både ME-pasienter og innen Autist-spekteret. I dette innlegget skal vi se litt på hva GcMAF er for ett medikament og hva dens virkningsmekanismer er. Altså en introduksjon. Innlegget er langt, se oppsummering av de viktigeste punktene. Jeg gjør oppmerksom på at kildemateriale er preget av kontroversielle og uenigheter for eksempel blant annet forskere, noe som ikke er uvanlig i den medisinske verden (noe vi vil se i del II).

Det har vært mye snakk om hva GcMAF er og også det mye omtalte gener og genotyper. DBP/Gc genotype er ikke det samme som vitamin D reseptor (VDR) genotype.

Hva er GcMAF?

GcMAF er en makrofag aktiverende faktor som har blitt identifisert som et protein derivert fra vitamin D binding protein.

GcMAF er synonymt for DBF-MAF (vitamin D-binding protein-makrofag aktiverende faktor)

Serum alfa-2-globolin (52 kDa) er ett av medlemmene i albumin familien. Det er kalt GC (group-specific component) eller GC-globulin og er identisk med human plasma protein VDBG (vitamin-D-binding alfa-globulin).

Gc genet ble isolert i 1993 og er det samme genet funnet av en annen forsker samme år kalt DBP (vitamin D-binding protein). Altså navn: DBP; GRD3; VDBG; VDBP; DBP/GC; GC

kilde

Vitamin D-binding protein er ett multi-funksjonelt plasmaprotein:

Det transporterer vitamin D og dens metabolitter i blodet.
Binder actin
Binder fettsyrer
Kontrollerer beinutvikling
Har flere mindre definerte aktiviteter med å modulere immun og inflammasjon-responser.

Yamamoto og Homma demonstrerte i 1991 at vitamin D binding protein er ett forstadium til makrofag-aktiverende faktor (MAF), som forsterker aktiviteten til makrofager.

Generering av den makrofag-aktiverende faktoren er kalt DBF-MAF eller GcMAF (Gc protein-derivert makrofag aktiverende faktor), og er påvirket etter omdannelse av membran glykosidase fra B- og T-celler og krever en selektiv fjerning av galaktose og sialic syre samt fra ett tredje domene.

Kew og Webster rapporterte i 1988 at Gc-globolinet i serum er av hovedglobulinene til å skape en kjemisk gradient som en forsterkende faktor og har muligens en funksjon som en kjemotaktisk oppregulerer av aktiviteten av peptider som er derivert fra C5 (komplementfaktor C5).

Det er ikke Gc-globolinet i seg selv som induserer denne gradienten til neutrofile celler men forsterker den kjemotaktiske neutrofilaktiviteten til C5 og dens derivat C5a-des-Arg.

DBP-MAF har blitt vist til å være ett «cytokin» som inviterer til benbygning ved å aktivisere osteoclats og denne aktiviteten er ikke påvirket av å binde vitamin D. I en studie ble det vist at mutasjon i rotter og mus som medførte ostepestrose hadde dårlig omdanning av DBP til DBP-MAF. Studien viste også at ved å tilføre Gc-MAF bedret tilstanden.

Forskere i 2002 rapportert at DBP-MAF kan hindre angiogenese, ved at det virker på endotelium og stimulerer makrofager til å angripe endoteliske celler og tumor celler.

MAF (makrofag aktiverende faktor):

MAF aktivitet ble i utgangspunktet observert i cellekultur av lymfocytter eller aktivering av celler ved celledelingen og antigener.

MAF aktiverer makrofagene noe som medfører at de kan agere som cytotoksiske celler som uspesifikt dreper tumorceller.

MAF er mer eller mindre en operativ definisjon for en spesifikk biologisk aktivitet enn ett navn for en bestemt faktor.

Hovedfaktoren som står ansvarlig for MAF aktivitet er IFN-gamma. Noe av aktiviteten er som følge av GM-CFS eller M-CFS, eller andre faktorer.

I tillegg har en rekke andre biokjemiske ikke karakteriserte faktorer blitt vist til å medføre MAF aktivitet. Noen av disse faktorene som normalt ikke er klassifisert som cytokiner, inkluderer akutt-fase-proteiner som C-reaktiv protein (CRP).

GM-CFS: Granulocyt-makrofag coloni stimmulerende faktor: Granulocytter eller også kjent som granulære leukocytter (neutrofile, eosinofile og basofile), da de inneholder ett mangfold av enzymer og proteiner i cytoplasma som dreper mikroorganismer.

Kilde

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Yamamoto og patenten (III domene) (1990):

In vitro enzymatic conversion of glycosylated human vitamin D binding protein to a potent macrophage activating factor

Abstract

A novel, potent macrophage activating factor is prepared in vitro by treating glycosylated human group-specific component, also known as human vitamin D-binding protein, with glycosidases. Group-specific component, which is isolated from retired blood by known procedures, is thus readily converted to a highly potent macrophage activating factor.

Videre kan vi lese (noen utdrag, se kort oppsummering nederst):

BACKGROUND OF THE INVENTION

Inflammatory Response Results in Activation of Macrophages

Microbial infections of various tissues cause inflammation which results in chemotaxis and activation of phagocytes. Inflamed tissues release lysophospholipids due to activation of phospholipase A. Inflamed cancerous tissues produce alkyl-lysophospholipids and alkylglycerols as well as lysophospholipids, because cancerous cells contain alkylphospholipids and monoalkyldiacylglyercols. These lysophospholipids and alkylglycerols, degradation products of membranous lipids in the inflamed normal and cancerous tissues, are potent macrophage activating agents (Yamamoto et al., Cancer Res. 47:2008, 1987; Yamamoto et al., Cancer Immunol. Immunother. 25:185, 1987; Yamamoto et al., Cancer Res. 24:6044, 1988).

Administration of lysophospholipids (5-20 .mu.g/mouse) and alkylglycerols (10-100 ng/mouse) to mice activates macrophages to phagocytize immunoglobulin G-coated sheep red blood cells. The macrophages phagocytize the target red blood cells via their receptors recognizing the Fc portion of the immunoglobulin G but not the C3b portion of the complement (Yamamoto et al., Cancer Res. 47:2008, 1987).

In vitro treatment of mouse peritoneal macrophages alone with lysophospholipids or alkylglycerols results in no enhanced ingestion activity (Yamamoto et al., Cancer Res. 48:6044, 1988). However, incubation of peritoneal cells (mixture of macrophages and B and T lymphocytes) with lysophospholipids or alkylglycerols for 2-3 hours produces markedly enhanced Fc-receptor-mediated phagocytic activity of macrophages (Yamamoto et al., Cancer Res. 47:2008, 1987; Yamamoto et al., Cancer Res. 48:6044, 1988).

Incubation of macrophages with lysophospholipid- or alkylglycerol-treated B and T lymphocytes in a medium containing 10% fetal calf serum developed a greatly enhanced phagocytic activity of macrophages (Yamamoto et al., Cancer Res. 48:6044, 1988). Analysis of macrophage activating signal transmission among the nonadherent (B and T) lymphocytes has revealed that lysophospholipid- or alkylglycerol-treated B-cells can transmit a signalling factor to T-cells; in turn, the T-cells modify the factor to yield a new factor, which is capable of the ultimate stimulation of macrophages for ingestion capability (Yamamoto et al., Cancer Res. 48:6044, 1988).

Human Vitamin D-Binding Protein

The human vitamin D-binding protein, also known as «group-specific component» or «Gc protein», is an evolutionary conserved glycoprotein. It is a genetically polymorphic plasma protein having a relative molecular weight of about 52,000, normally constituting about 0.5% of the plasma proteins in man. The plasma concentration is generally about 260 .mu.g/ml. Polymorphism of the Gc protein is demonstrable by gel electrophoretic analysis, which reveals two major phenotypes: Gc1 and Gc2 Gc1 is further divided into Gc1f and Gc1s subtypes (…)

Coopenhaver et al., Arch. Biochem. Biophys. 226, 218-223 (1983) reported that the post-translational glycosylation difference occurs at a threonine residue, which appeared in a region of the protein having an amino acid difference between Gc1 and Gc2. While a CNBr fragment of Gc1 was found to contain N-acetylgalactosamine, no detectable galactosamine was reported in the homologous Gc2 CNBr fragment according to the method and criteria used. The Gc1 CNBr fragment further contained sialic acid, which was missing from the homologous region of Gc2.

Viau et al., Biochem. Biophys. Res. Commun. 117, 324-331 (1983), reported a predicted structure for the O-glucosidically linked glycan of Gc1, containing a linear arrangement of sialic acid, galactose and N-acetylgalactosamine linked to a serine or threonine residue.

The Gc protein may be purified by a variety of means, which have been reported in the literature. For example, the Gc protein may be purified by 25-hydroxy-vitamin D.sub.3 -Sepharose.RTM. affinity chromatography from retired blood of the American Red Cross (Link, et al., Anal. Biochem. 157:262, 1986). The Gc protein can also be purified by actin-agarose affinity chromatography due to its specific binding capacity to actin (Haddad et al., Bioch J. 218:805, 1984).

Despite the characterization and intensive study of the human vitamin D-binding protein, and the existence of ready methods for its purification, the enzymatic conversion of this protein to a potent macrophage activity factor has not been demonstrated until the present invention.

SUMMARY OF THE INVENTION

A process for the production of a potent macrophage activating factor is provided. Human vitamin D-binding protein, which is identical to group-specific component in human serum, is a precursor of the macrophage activating factor. Group-specific component is converted to the factor by the action of glycosidases of B and T cells.

According to a process for preparing macrophage activating factor, group-specific component is contacted in vitro (i) with .beta.-galactosidase, or (ii) with .beta.-galactosidase in combination with sialidase, .alpha.-mannosidase or a mixture thereof. A potent macrophage activating factor is obtained in large quantities

According to one embodiment of the invention, group-specific component of phenotype Gc1, subtype Gc1f, is contacted with .beta.-galactosidase and sialidase to provide the macrophage activating factor. According to another embodiment, group-specific component of phenotype Gc1, subtype Gc1s, is contacted with .beta.-galactosidase and .alpha.-mannosidase. Preferably, group-specific component of phenotype Gc1, subtype Gc1s, is contacted with not only .beta.-galactosidase and .alpha.-mannosidase, but also sialidase, to ensure the conversion of the Gc1s variant (hereinafter Gc1s*) which contains sialic acid in lieu of .alpha.-mannose. Gc1s*, like Gc1f, requires treatment with .beta.-galactosidase and sialidase for conversion to macrophage activating factor. In yet another embodiment, group-specific component of phenotype Gc2 is contacted with .beta.-galactosidase alone to form the macrophage activating factor. Preferably, the macrophage activating factor is prepared by contacting pooled group-specific components comprising a mixture of Gc1f, Gc1s (Gc1s*) and Gc2 with all three enzymes to obtain the macrophage activating factor.

The invention also relates to a macrophage activating factor prepared according to the above process or any embodiment thereof, and compositions comprising the macrophage activating factor in combination with a pharmaceutically acceptable carrier.

The invention further relates to a method for inducing macrophage activation in an individual in need thereof by administering to such an individual macrophage activating effective amount of the novel macrophage activating factor.

«Group-specific component» or «Gc protein» as used herein means the genetically polymorphic glycoprotein, also known as «vitamin D-binding protein», including all genetic variations thereof, such as Gc2, Gc1, and subtypes such as Gc1f, Gc1s and Gc1s*. The singular expression «group-specific component» or «Gc protein» is thus understood to encompass all such variants, unless stated otherwise.

By «macrophage activation» is meant the stimulation of macrophages to an increased level of phagocytic activity.

DETAILED DESCRIPTION OF THE INVENTION

A serum factor, which has been identified as human group-specific component, is converted to a macrophage activating factor by the action of B and T cell glycosidases. Human group-specific component exists as a polypeptide having attached thereto specific oligosaccharide moieties, certain of which are readily removable by treatment with readily available glycosidases. These glycosidases are equivalent to the functions of B and T cells upon the Gc protein. Upon treatment with specific glycosidases, group-specific component is unexpectedly converted to a highly potent macrophage activating factor. Thus, efficient conversion of Gc protein to the macrophage activating factor is achieved in vitro, in the absence of intact B- and T-cells. The novel macrophage activating factor formed by the enzymatic treatment of Gc protein is substantially pure and of such high potency that administration to a host of even a trace amount (500 picogram/kg of body weight) results in greatly enhanced phagocytic macrophage activity. Since the enzymatic generation of the novel factor bypasses the functions of B-and T-cells in macrophage activation, it has utility as a therapeutic agent for inducing macrophage activation, particularly in individuals afflicted with immunodeficient diseases, cancer or other immunocompromising diseases characterized by impaired B- or T-cell function.

T-cell lymphokine macrophage activating factor, also known as .gamma.-interferon, is generated by lymphokine-producing T-cells in small amounts, or is obtained by genetic engineering. The novel macrophage activating factor of the invention, on the other hand, may be readily obtained from Gc protein which may be purified from the plasma of retired human blood in large volume, according to known purification procedures.

The human Gc protein phenotypes Gc1 and Gc2, and the Gc1 subtypes Gc1f and Gc1s, are expressed inter alia as differences in the oligosaccharides attached to the polypeptide portion of the Gc molecule. The novel macrophage activating factor of the invention may be efficiently produced from Gc1f or Gc1s protein by incubation with a combination of .beta.-galactosidase and sialidase, or a combination of .beta.-galactosidase and .alpha.-mannosidase, respectively. If the Gc1s comprises at least in part the Gc1s variant, Gc1s*, which contains sialic acid (N-acetyl-D-neuramic acid, or «NeuNAc») in lieu of .alpha.-mannose, the mixture of enzymes utilized to treat the Gc1s/Gc1s* mixture advantageously also includes sialidase. Treatment of the Gc2 protein with .beta.-galactosidase alone efficiently yields the macrophage activating factor. The in vitro conversion of Gc protein to macrophage activating factor by the action of commercially available enzymes is so efficient that an extremely high activity of macrophage activating factor is obtained.

Due to its genetic polymorphism, Gc protein obtained from pooled retired human blood will likely contain all three principal Gc types. Complete conversion of a mixture of Gc proteins to macrophage activating factor may thus most expeditiously be achieved by treatment with all three enzymes, as an enzyme mixture.

All three principal Gc types–Gc1s, Gc1f and Gc2–differ in the nature of the appended oligosaccharide, although it is believed that most Gc2 molecules are unglyosylated. Only the glycosylated form of Gc2 is a precursor for macrophage activating factor according to the process described herein. Incubation of each of Gc1f, Gc1s and Gc2 molecules with galactose-specific lectin beads absorbed all three macrophage activator precursor types. Thus, the outer oligosaccharide moiety of each of the three principal human Gc types is believed to be galactose.

Gc2 protein treated with .beta.-galactosidase alone efficiently activates macrophages. Therefore, removal of galactose from Gc2 protein, to the extent the molecule is present in its glycosylated form, results in the formation of the macrophage activating factor. On the other hand, two glycosidases are required to convert the Gc1 proteins to macrophage activating factor. Conversion of Gc1f to the macrophage activity factor requires incubation with the combination of .beta.-galactosidase and sialidase. Conversion of Gc1s requires .beta.-galactosidase and .alpha.-mannosidase (or .beta.-galactosidase and sialidase, in the case of Gc1s*).

The innermost sugar of the oligosaccharide moiety of Gc1 protein is N-acetylgalactosamine (Coppenhaver et al., Arch Biochem. Biophys. 226, 218-223, 1983). Treatment of Gc1 protein with endo-N-acetylglucosaminidase, which results in the cleavage of the N-acetylgalactosamine, results in a molecule which cannot be then converted to macrophage activating factor.

It is believed that the Gc protein phenotypes and subtypes are characterized as glycoproteins having the following oligosaccharide structures linked to an amino acid residue of the protein portion of the molecule

Human Gc protein of high purity for use in the process of the invention is most readily prepared by 25-hydroxyvitamin D.sub.3 -Sepharose.RTM. affinity chromatography from retired blood according to the procedure of Link et al., Anal. Buiochem. 157, 262 (1986), the entire disclosure of which is incorporated herein by reference. The Gc protein may also be purified by actin-agarose affinity chromatography according to the procedure of Haddad et al., Biochem. J. 218, 805 (1984), which takes advantage of the binding specificity of Gc protein for actin. The entire disclosure of Haddad et al., is incorporated herein by reference. Other methods of obtaining Gc protein in high purity are reported in the literature.

Conversion of Gc protein to macrophage activating factor may be conducted in any vessel suitable for enzymatic reactions. It is preferred that sialidase is utilized in insoluble form, e.g., attached to beaded agarose (Sigma Chemical Co., cat. no. N-4483), to avoid contamination of the resulting macrophage activating factor with sialidase fragments of similar molecular weight. The macrophage activating factor may be produced by adding the appropriate enzyme(s) to Gc protein in a liquid medium, followed by subsequent filtration of the liquid to recover the macrophage activating factor. For example, the enzyme-Gc protein reaction mixture may be passed through a sterilized 100 kDa cut off filter (e.g. Amicon YM 100) to remove the immobilized sialidase, .beta.-galactosidase (MW=540 kDa) and .alpha.-mannosidase (MW=190 kDa). The filtrate contains substantially pure macrophage activating factor of high activity.

Regardless of whether immobilized or liquid phase enzyme is utilized, it is desired to pass the product mixture through an ultrafilter, preferably a filter having a pore size no larger than about 0.45.mu., to provide an aseptic preparation of macrophage activating factor.

Without wishing to be bound by any theory, it is believed that B-cells possess the function corresponding to .beta.-galactosidase, and that T-cells carry the functions corresponding to sialidase and .alpha.-mannosidase. It is believed that Gc protein is modified in vivo in an ordered sequence by the membranous enzymes of B and T lymphocytes to yield macrophage activating factor.

Activation of macrophages, which is characterized by their consequent enhanced phagocytic activity, is the first major step in a host’s immune defense mechanism. Macrophage activation requires B and T lymphocyte functions, which modify Gc protein in a step-wise fashion, to yield the novel macrophage activating factor. Since the glycosidases used for in vitro conversion of Gc protein to macrophage activating factor according to the present invention correspond to the B- and the T-cell function required for production of macrophage activating factor, the in vitro enzymatic generation of the macrophage activating factor bypasses the functions of B- and T-cells. Thus, in vitro enzymatic-generated macrophage activating factor may be used for the therapy of immuno-deficient diseases, cancer and other disease conditions characterized by the immunocompromise of the afflicted individual. Moreover, since the herein described in vitro-generated macrophage activating factor is of human origin, side effects, such as immunogenicity, are believed to be minimal.

To minimize any possible immunologic reaction from administration of the macrophage activating factor, it is preferred that individuals of phenotype Gc1 would receive only Gc1 -derived macrophage activating factor. Similarly, the risk of immunologic reaction in Gc2 individuals would be minimized by administering only Gc2-derived macrophage activating factor.

The novel macrophage activating factor is also believed useful in the treatment of disorders characterized by a disruption or loss of B- or T-cell function. Such disorders may be characterized by a lack of macrophage activation. Addition of exogenous macrophage activating factor of the invention will result in the restoration of macrophage activity, even in the absence of complete B- or T-cell function.

The macrophage activating factor may be administered to an individual to induce macrophage activation, either alone or in combination with other therapies. The amount of macrophage activating factor administered depends on a variety of factors, including the potency of the agent, the duration and degree of macrophage activation sought, the size and weight of the subject, the nature of the underlying affliction, and the like. Generally, administration of as little as about 0.5 ng of factor per kg of the subject’s body weight will result in substantial macrophage activation. According to one treatment, a human subject may receive as little as about 30-35 ng of macrophage activating factor every three to five days to maintain a significant level of macrophage activation.

The macrophage activating factor may be administered by any convenient means which will result in delivery to the circulation of an amount of the factor sufficient to induce substantial macrophage activation. For example, it may be delivered by intravenous or intramuscular injection. Intravenous administration is presently preferred as the route of administration.

The macrophage activating factor may be taken up in pharmaceutically acceptable carriers, particularly those carriers suitable for delivery of proteinaceous pharmaceuticals. The factor is soluble in water or saline solution. Thus, the preferred formulation for pharmacological use comprises a saline solution of the agent. The formulation may optionally contain other agents, such as adjuvants to maintain osmotic balance. For example, a typical carrier for injection may comprise an aqueous solution of 0.9% NaCl or phosphate buffered saline (a 0.9% NaCl aqueous solution containing 0.01M sodium phosphate, .apprxeq.pH 7.0).

 Bilde: hentet fra publikasjon les her

***

 Gc gener og VDR-gener i en studie med osteoporosis (benskjørhet) sier innledende:

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Sitat:

As a candidate gene for osteoporosis, we studied vitamin D binding protein (DBP, or group-specific component, Gc), which binds to and transports vitamin D to target tissues to maintain calcium homeostasis through the vitamin D endocrine system. DBP can also be converted to DBP-macrophage activating factor (DBP-MAF), which mediates bone resorption by directly activating osteoclasts.

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Det kan kanskje virke forvirrende med å sette dette i dette innlegget, men forklarer likevel sammenhenger og forskjeller på genotypene vedrørende GcMAF og VDR genotype.

På den andre siden er VDR-reseptoren og denne studien interessant i forhold til D-vitaminer. Flere med ME/CFS blir dårligere av vitamin D tilskudd, og Marshall protokollen (MP) baserer sin behandling på at all vitamin D kilder skal unngås.

***

Virker GcMAF?

Vel som det fremgår i innledende tekst er dette noe som naturlig skjer i kroppen, men ved å tilføre GcMAF kan dette øke makrofagaktiviteten…

Kenny De Meirleir and Yamamoto krangler om genotyper – Low and high responder:

I bloggen CFS Central kan vi lese om dette:

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Sitat:

Dr. Nobuto Yamamoto, the world’s foremost expert on GcMAF, says in his experience it makes absolutely no difference whether patients have mutations in these two SNPS. “The efficacy of GcMAF depends on the capability of the patient’s macrophages [to be] activated,” he explained in an email. “Macrophage activation [has] nothing to do with VDR polymorphism.” In fact, he wrote, an inability to respond to GcMAF would be fatal

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Aktivering av makrofagene har altså ingenting å gjøre med VDR polymorfisme.

————————————————————————————————————————————————————-

Sitat:

In the large number of patients who’ve been treated with GcMAF, Yamamoto has never observed an inability to respond to the medication.

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Her sier Yamamoto videre at han aldri har observert at en ikke responderer på behandling av GcMAF.

***

 Noen Ord og uttrykk:

Glycosidases

alfa-N-acetylgalactosaminidase = Nagalase blokker Gc-proteinet til å omdanne GcMAF

alkylglycerols: aktiverer stamcelle-produksjon av blant annet hvite og røde blodceller.

Lysophospholipids: har funksjon med blant annet frigjøring av kalsium, forhindre celledød og øke cellespredning.

Angiogenesis

Oppsummering:

Human vitamin D-binding protein (Gc-protein) i menneskers serum er ett forstadium til makrofag aktiverende faktor (MAF), som dannes ved enzymatisk nedbryting av bestemte sukkerarter som finnes på B og T-celler. Ved å fjerne disse enzymene in vitro kan en altså lage GcMAF som har til hensikt å aktivisere makrofagene til økt fagocytose i bekjempelse av for eksempel kreftceller og infeksjoner.

Gc-proteinet er genetisk polymorf med to hoved fenotyper/genotyper: Gc1 med subgrupper Gc1f og Gc1s og Gc2.

“In vitro enzymatic-generated macrophage activating factor may be used for the therapy of immuno-deficient diseases, cancer and other disease conditions characterized by the immunocompromise of the afflicted individual. Moreover, since the herein described in vitro-generated macrophage activating factor is of human origin, side effects, such as immunogenicity, are believed to be minimal.

To minimize any possible immunologic reaction from administration of the macrophage activating factor, it is preferred that individuals of phenotype Gc1 would receive only Gc1 -derived macrophage activating factor. Similarly, the risk of immunologic reaction in Gc2 individuals would be minimized by administering only Gc2-derived macrophage activating factor.

The novel macrophage activating factor is also believed useful in the treatment of disorders characterized by a disruption or loss of B- or T-cell function. Such disorders may be characterized by a lack of macrophage activation. Addition of exogenous macrophage activating factor of the invention will result in the restoration of macrophage activity, even in the absence of complete B- or T-cell function.

The macrophage activating factor may be administered to an individual to induce macrophage activation, either alone or in combination with other therapies. The amount of macrophage activating factor administered depends on a variety of factors, including the potency of the agent, the duration and degree of macrophage activation sought, the size and weight of the subject, the nature of the underlying affliction, and the like. Generally, administration of as little as about 0.5 ng of factor per kg of the subject’s body weight will result in substantial macrophage activation. According to one treatment, a human subject may receive as little as about 30-35 ng of macrophage activating factor every three to five days to maintain a significant level of macrophage activation.

The macrophage activating factor may be administered by any convenient means which will result in delivery to the circulation of an amount of the factor sufficient to induce substantial macrophage activation. For example, it may be delivered by intravenous or intramuscular injection. Intravenous administration is presently preferred as the route of administration.”

Som vi kan lese her vil GcMAF være særs gunstig i individer med lave antall B og T-celler, men vil likevel medføre en økning i makrofagaktiviteten ved injeksjoner av enzymbehandlet Gc-protein fra menneskelig blodserum ved tilstedeværelse av normalt antall B og T-celler.

Yamamoto sier i sin patentsøknad at bivirkningene er minimale om prosedyrene for tillaging er oppskriftsmessig, men presiserer likevel at det er foretrukket at en tar hensyn til mottagers fenotype. Har du Gc-protein fenotype Gc1 er det foretrukket at du får GcMAF med Gc1 fenotype fra blodplasmagiver for å redusere immunresponsreaksjoner.

Med oppskriftsmessig tillaging av GcMAF fordrer prosedyrer som hindrer kontaminering og at produktet er aseptisk, filtrert med mer.

Dosering av GcMAF bør være etter kroppsvekt.

GcMAF behandling på ME-pasienter:

Som det fremgår av innlegget blir GcMAF brukt som behandlingsinvensjon på ME-pasienter av enkelte behandlere. Den belgiske legen Kenny De Meirleir (KDM), Dr. Enlander og Dr. Cheney har protokoller for GcMAF behandling. Behandlingsregimet kom etter at det ble funnet gammaretrovirus (XMRV og P-MLVs) i ME-pasienter og var da som ett alternativ for antiretrovirale medisiner (ARVs).

Retropositive individer ble satt på GcMAF etter målinger av nagalase og VDR-gen analyse. Som vi ser av innlegget har ikke VDR-genotype ifølge Yamamoto ingen betydning om du er en høy eller lav responder av GcMAF.

I neste innlegg skal vi se på blant annet på effekten av behandlingstilnærming ved bruk av GcMAF på ME-pasienter.

4 kommentarer om “På ME-fronten: Behandling med GcMAF – en intro

  1. Ok, men da venter jeg med å si noe fornuftig siden jeg ikke har lest det neste innlegget.🙂

    Du skal ha ros for innsatsen. Og det mener jeg! Skjønner jo at du koser deg med dette men ikke slit deg ut nå.
    🙂

    1. Heia kjekken😀

      jada vi får se – har vel omtrent ca 20 faner oppe, så her gjelder det å ha tunga rett i munnen… pæser som f… hehe….

      Omfattende datamateriale og masse bråk rundt i huset. Så dundrer hue med Linkin park – hehe en real headbanging… minstemann skulle nok ønska å ha bytta mammaen sin akkurat nu *glis*😆

      VM i luftgitar neste:mrgreen:

      PS! har sovd…😀

      Skal du høre sangstrofa? what in hell are u waiting for…..🙄

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