Spanish CFS patent

[Daffodil]

http://www.faqs.org/patents/app/20100331261

 

[maryb]

Thanks daffodil - hope someone can sum it up for us not up to reading it

 

[eric_s]

I'm really a total layman, but i can give it a try

It's about a substance called alpha-1-antitrypsin. It seems they want to protect a method or methods of how to produce a drug using that substance (alpha-1-antitrypsin) and how to treat ME/CFS with that drug.

A bit further down they say about alpha-1-antitrypsin

[0030]Alpha-1-antitrypsin (AAT) is a glycoprotein secreted in hepatocytes, and is normally present in high concentrations in serum and in most tissues, where it acts as a serine protease inhibitor. The reference values for AAT in the serum of healthy subjects are 0.83-2.00 g/l (Kratz A, et al., Laboratory Reference Values, N Engl J Med 2004; 315(15): 1548-1563). Apart from its activity as a protease inhibitor, AAT has been described as possibly having an important anti-inflammatory biological function, as it has a significant capacity to inhibit many inflammation mediators and oxidising radicals (Brantly M., Alpha1-antitrypsin: not just an antiprotease: extending the half-life of a natural anti-inflammatory molecule by conjugation with polyethylene glycol, Am J Respir Cell Mol Biol 2002; 27(6): 652-654).

Here they say what they think AAT can do

[0034]To check whether the inhibition of elastase by AAT could prevent RNase L degradation, the inventors carried out various studies using in vitro PBMC culture from patients with CFS together with AAT concentrates. Based on these studies, the inventors established that PBMC extracts from patients with CFS show raised elastase activity, far higher than that of PBMC extracts from healthy subjects.[...]

[0035]The inventors also discovered that AAT was capable of substantially inhibiting the intracellular elastase activity of cultures of PBMC from patients with CFS.[...]

[0036]In addition, the inventors established that AAT prevented degradation of 83 kDa RNase L, to generate the hyperactive form of 37 kDa RNase L, in PBMC cultures from patients with CFS.[...]

[0037]The present inventors found that AAT activated the expression of genes involved in the 2-5A synthetase pathway so that the administration of exogenous AAT could re-establish normal RNase L activity and prevent its proteolysis in the PBMCs of patients with CFS.
[...]
[0039]The inventors also found that AAT inhibited the expression of metallothionines, and therefore the administration of exogenous AAT could reduce activation of the proinflammatory pathways of the PBMCs of patients with CFS.
[...]
A fall in NO production, due to a reduction in the expression of metallothionines induced by AAT could be another beneficial action of this protein in the context of patients with CFS.
[...]

EXAMPLE

[0049]While waiting for the results obtained in vitro, the inventors, having been granted a compassionate use authorisation, administered a preparation based on AAT to a patient diagnosed with CFS.

[0050]A female patient was diagnosed with CFS in 2003 having met the Fukuda diagnostic criteria, and other medical processes inducing chronic fatigue, such as endocrine, infectious, neoplastic and/or psychiatric disorders having been ruled out. Before beginning treatment with AAT concentrate, the patient had an elastase concentration in PBMC of 1459 U/mg (units of activity per milligram of PBMC extract); in the functional reserve assessment test, the patient exhibited a maximum oxygen consumption of 17.2 ml/kg/min (63.5% of theoretical), a maximum power of 64 watts (54.0% of theoretical), a maximum heart rate of 149 beats (87.6% of theoretical); and in the neurocognitive dysfunction study, showed very serious cognitive impairment. The patient was subjected to therapy with intravenous infusions of the AAT-based preparation (60 mg/kg of body weight weekly) for a period of eight weeks. At the end of the treatment, the patient exhibited an elastase concentration in PBMC of 134 U/mg (units of activity per milligram of PBMC extract); in the functional reserve assessment test, the patient exhibited a maximum oxygen consumption of 16.4 ml/kg/min (60.6% of theoretical), maximum power of 85 watts (71.7% of theoretical), a maximum heart rate of 151 beats (88.8% of theoretical); and in the neurocognitive dysfunction study displayed serious cognitive impairment. As a general conclusion, after treatment with the AAT-based preparation, the patient showed clear clinical improvement, she returned to work, experienced less fatigue and exhibited improved tolerance of physical exercise and slightly reduced cognitive dysfunction.

[0051]It is therefore demonstrated that by means of the present invention, patients with CFS can be effectively treated with drugs prepared on the basis of AAT. These patients would be affected by chronic inflammation of immunological cells and, according to the present invention, AAT inhibits elastase and thus avoids RNase L degradation, so preventing ion channel deregulation, which is supposedly responsible for the symptomology associated with CFS. In addition, and according to the results obtained in vitro, AAT could regulate the expression of particular genes associated with the immunological system to re-establish normal functioning of the immunological system and reduce activation of the proinflammatory pathways.

I wonder why we haven't heard more about it if it worked so well. There are so many people with ME/CFS in Barcelona, i'm sure there would be enough people willing to try it.

Also read what Dr. Enlander said at the bottom of the page.

 

[maryb]

Thank you eric. So we'll have to wait for proper trials of this drug, looks interesting , but Fukuda criteria and only 1 patient ??

 

[justy]

Im not sure how they will patent this, it is already in use as a therapy to treat lung disease caused by alpha-1-antitrypsin deficiency which can cause emphysema and other lung disorders (it is a genetic defect whereby the person does not produce enough alpha 1 antytrypsin to stop lung inflammation) so far it has not been linked with any other inflammatory disorders.
I was tested for this because i have a chronic lung problem, my results came back on the border of normal and low, dont know what that means. and despite continuing lung issues i have not been offered it as a therapy.
Justy.

 

[Klmrav]

Daffodil, thanks for posting this thread. I have been interested in A1AT deficiency since I found out I have one defective gene (type MZ). A1AT cleaves elastase. My elastase results from VIPdx were over 2000. Elastase cleaves RNaseL. I also express the LMW RNaseL. Although the gene is not the cause of our illness, it is probably worse in those with A1AD.

@ Justy, check out the alpha-1 foundation website for free, confidential A1AT phenotyping from the ACT program at MUSC.

Does anyone think it would be helpful to put up a survey?

Dr. Blanco has done a number of A1AT studies and a few regarding fibromyalgia; a quick pubmed search will bring them up.

 

[valentinelynx]

Am I reading that wrong? In the results listed, the single patient in this unblinded, uncontrolled study showed an improvement in her maximum work output on one test. No significant improvement in oxygen consumption, no improvement in maximum heart rate, no improvement in cognitive function. That she returned to work is great. The rest I don't know if it is an assumption on the part of the writer or quantifiable: "clear clinical improvement, ..., experienced less fatigue and exhibited improved tolerance of physical exercise and slightly reduced cognitive dysfunction." In any case, there are lots of things that have helped one person, or several people, some of which are absurd and have no scientific justification. Without more studies, I don't see what's so exciting about this. I certainly don't think this statement is supported: "It is therefore demonstrated that by means of the present invention, patients [note plural] with CFS can be effectively treated with drugs prepared on the basis of AAT". It showed that one person got better after a rather dramatic, exciting intervention (it's new, gots lots of science behind it, it's IV, done with lots of hard tests...). Unless I'm missing something.