Calvinball is a game invented by Calvin in which one makes the rules up as one goes along. Rules cannot be used twice. No Calvinball game is like another. The game may involve wickets, mallets, volleyballs, and additional equipment as well as masks.
A random reference on my part, sorry. Since medical research is not Calvinball, eventually MS and CCSVI will get figured out and the correct treatment will be figured out, whatever that is. This will be very good for the generation in which this happens, and painfully lousy for the generation that just misses. Honestly I think we're close.
Randomocitousness is mainly tolerated in these environs.
The single negative study has broken links. Mysteriously, they all seem to point at the same, wrong paper, which also seems to be open-access.
Nissen KK, Laska MJ, Hansen B, Pedersen FS, Nexø BA: No additional copies of HERV-Fc1 in the germ line of multiple sclerosis patients.
Virol J 2012, 9:1-4. PubMed Abstract | BioMed Central Full Text | PubMed Central Full Text OpenURL
GNbAC1, a Humanized Monoclonal Antibody Against the Envelope Protein of Multiple Sclerosis—Associated Endogenous Retrovirus: A First-in-Humans Randomized Clinical Study
François Curtin, MDemail address
Alois B. Lang, PhD
Hervé Perron, PhD
Marion Laumonier, MSc
Virginie Vidal, MSc
Hervé C. Porchet, MD
Hans-Peter Hartung, MD
Accepted 12 November 2012. published online 03 December 2012.
Human endogenous retrovirus (HERV) genes represent about 8% of the human genome. A member of the HERV family W, the Multiple Sclerosis–Associated Retrovirus (MSRV) gene, encodes an envelope protein (Env), which can activate a proinflammatory and autoimmune cascade through its interaction with Toll-like receptor 4. Due to its proinflammatory property and an inhibitory effect on oligodendrocyte precursor cell differentiation, the MSRV-Env protein could play a crucial role in the pathogeny of multiple sclerosis. GNbAC1 is a humanized monoclonal antibody of the immunoglobulin G4 type, which is directed against MSRV-Env. After validation of the MSRV-Env as a therapeutic target in preclinical experimental models, a clinical development program was initiated.
This study evaluated the safety profile, pharmacokinetic parameters, and immunogenicity of GNbAC1 in healthy male volunteers.
In this first-in-humans, Phase I, randomized, double-blind, placebo-controlled, dose-escalation study, each subject received a single dose of IV GNbAC1 0.0025, 0.025, 0.15, 0.6, 2, or 6 mg/kg or inactive vehicle (placebo), infused over 1 hour. Tolerability and other laboratory parameters were observed, and regular blood sampling was performed, to study the pharmacokinetic properties and immunogenicity of this monoclonal antibody.
A total of 33 male subjects (mean age, 44 years) completed the study. GNbAC1 was well tolerated after dosing in all subjects and in each dose cohort. Only minor and nonspecific adverse events (AEs) were recorded; no serious AEs were reported. Pharmacokinetic data show a dose-linear pharmacokinetic profile. The mean elimination half-life ranged between 19 and 26 days, with therapeutically efficient concentrations maintained over a 4-week periods at doses of 2 and 6 mg/kg. No emergence of anti-GNbAC1 antibodies were detected after dosing in any subject over the entire observation period of 64 days.
In these healthy male subjects, the safety and pharmacokinetic profiles of GNbAC1 appeared favorable. These findings are expected to allow for the launch of a Phase II development program for this innovative therapeutic approach in patients with multiple sclerosis. ClinicalTrials.gov identifier: NCT01699555.
seems interesting, because they are expecting Phase-II. If it's that good, maybe Phase-II and Phase III can be combined. However, efficacy in this case is limited to the reduction of incidence of the MS-associated retrovirus. Whatever affect this may have clinically is not elucidated yet. Seems to me it still could turn into another blind alley.
The prevalence study cited is interesting to me as an anecdote. The prevalence in the Orkney islands seems to be higher even than Northern Ireland. My ancestors came from the Republic, which seems to be lower, but I visited the Orkneys only a few years before my first persistent symptoms appeared. If there is an environmental or pathogen connection to the Orkneys, I may have been exposed to it. My personal opinion is that something about this disease that influences it long-term is a cumulative phenomenon initially. Long-term course of the disease would depend on initial accumulation of some pathogen-exposure or environmental toxin exposure. That would possibly be coincident with exacerbations.