Oral Chelators

  • 17 Replies
  • 14771 Views
Oral Chelators
« on: April 30, 2011, 09:58:40 PM »
Oral chelators in transfusion-dependent thalassemia major patients may prevent or reverse iron overload complications
Blood Cells, Molecules, and Diseases
Kallistheni Farmaki, a, , Ioanna Tzoumaria and Christina Pappaa
a Thalassemia Unit, General Hospital of Corinth, 1,
Dervenakion, Corinth 20100, Greece
Received 10 March 2011;  revised 19 March 2011. 
(Communicated by G. Stamatoyannopoulos, M.D., Dr. Sci., 21 March 2011). 
Available online 29 April 2011.

Abstract
Combined chelation treatment may be a better approach for transfusion-dependent thalassemia major patients with iron overload complications because of increased efficacy. Combination therapy with desferrioxamine and deferiprone has already been reported to improve survival dramatically by reversing cardiac dysfunction and other endocrine complications. Some patients have intolerance or inconvenience to parenteral desferrioxamine. The hypothesis of this study was that combining two oral chelators, deferiprone and deferasirox, might lead to similar results. Following approval by the hospital ethical committee and a written informed consent from each patient, 16 patients who fulfilled the criteria participated in a study protocol for a period of up to 2 years. Efficacy measures analysis demonstrated a statistically significant decrease of total body iron load as estimated by serum ferritin, LIC and MRI T2* indices. Regarding the safety assessment, the incidence of adverse events was minor compared to the associated toxicity of monotherapy of each drug. No new onset of iron overload-related complications was demonstrated. A reversal of cardiac dysfunction was observed in 2/4 patients, while the mean LVEF increased significantly. Regarding endocrine assessment, in 2/8 patients with impaired glucose tolerance, we noted a significant decrease in the mean 2 h glucose in OGTT. Additionally an improvement in gonadal function was observed and one male and one female gave birth to two healthy children without hormonal stimulation. Combined oral chelation in thalassemia offers the promise of easier administration, better compliance and may lead to an improvement of patient quality of life by preventing or even reversing iron overload complications.

Keywords: Thalassemia major; Combined chelation; Deferiprone; Deferasirox; Iron overload complications

doi:10.1016/j.bcmd.2011.03.007 | How to Cite or Link Using DOI
Copyright © 2011 Elsevier Inc. All rights reserved.


*

Offline Sharmin

  • *****
  • 4155
  • Gender: Female
  • Little A
Re: Oral Chelators
« Reply #1 on: April 30, 2011, 10:09:53 PM »
This is very promising.  My son's iron levels have remained below 500 - for the most part since he began oral chelation. 
Thanks for sharing:)

Sharmin
Sharmin

*

Offline Andy Battaglia

  • *****
  • 8793
  • Gender: Male
  • Will thal rule you or will you rule thal?
Re: Oral Chelators
« Reply #2 on: April 30, 2011, 10:54:47 PM »
Is this the trial that was done at Lena's center?
Andy

All we are saying is give thals a chance.

Re: Oral Chelators
« Reply #3 on: July 06, 2011, 02:33:07 PM »
Oral chelators in transfusion-dependent thalassemia major patients may prevent or reverse iron overload complications

Effect of Deferiprone or Deferoxamine on Right Ventricular Function in Thalassemia Major Patients with Myocardial Iron Overload
Gillian C Smith , Francisco Alpendurada , John Paul Carpenter , Mohammed H Alam , Vasili Berdoukas , Markissia Karagiorgia , Vasili Ladis , Antonio Piga , Athanassios Aessopos , Efstathios D Gotsis , Mark A Tanner , Mark A Westwood , Renzo Galanello , Michael Roughton  and Dudley J Pennell

Journal of Cardiovascular Magnetic Resonance 2011, 13:34doi:10.1186/1532-429X-13-34

 
Published: 6 July 2011

Abstract (provisional)

Background
Thalassaemia major (TM) patients need regular blood transfusions that lead to accumulation of iron and death from heart failure. Deferiprone has been reported to be superior to deferoxamine for the removal of cardiac iron but little is known of their relative effects on the RV, which is being increasingly recognised as an important prognostic factor in cardiomyopathy. Therefore data from a prospective randomised controlled trial (RCT) comparing these chelators was retrospectively analysed to assess the RV responses to these drugs.

Methods
In the RCT, 61 TM patients were randomised to receive either deferiprone or deferoxamine monotherapy, and CMR scans for T2* and cardiac function were obtained. Data were re-analysed for RV volumes and function at baseline, and after 6 and 12 months of treatment.

Results
From baseline to 12 months, deferiprone reduced RV end systolic volume (ESV) from 37.7 to 34.2 mL (p=0.009), whilst RV ejection fraction (EF) increased from 69.6 to 71.4% (p=0.001). By contrast, deferoxamine showed no change in RVESV (38.1 to 39.1mL, p=0.38), or RVEF (70.0 to 69.9%, p=0.93). Analysis of between drugs treatment effects, showed significant improvements favouring deferiprone with a mean effect on RVESV of -4.48mL (p=0.009) and 2.69% for RVEF (p=0.013). The improvement in RVEF at 12 months was greater in patients with lower baseline EF values (p<0.001), with a significant difference in RVEF of 3.5% favouring deferiprone over deferoxamine (p=0.012).

Conclusion
In this retrospective analysis of a prospective randomized controlled trial, deferiprone monotherapy was superior to deferoxamine for improvement in RV EF and end-systolic volume. This improvement in the RV volumes and function may contribute to the improved cardiac outcomes seen with deferiprone.


*

Offline Dori

  • *****
  • 1443
Re: Oral Chelators
« Reply #4 on: July 06, 2011, 02:57:57 PM »
Andy, I think it is.

Re: Oral Chelators
« Reply #5 on: July 09, 2011, 05:34:02 PM »
Effect of Deferiprone or Deferoxamine on Right Ventricular Function in Thalassemia Major Patients with Myocardial Iron Overload

An optimal method of iron starvation of the obligate intracellular
pathogen, Chlamydia trachomatis.
Front Microbiol. 2011;2:20. Epub 2011 Feb 14.
Thompson CC, Carabeo RA.
SourceDivision of Cell and Molecular Biology, Centre for Molecular
Microbiology and Infection, Imperial College London London, UK.

Abstract
Iron is an essential cofactor in a number of critical biochemical
reactions, and as such, its acquisition, storage, and metabolism is
highly regulated in most organisms.
The obligate intracellular bacterium, Chlamydia trachomatis
experiences a developmental arrest when iron within the host is
depleted.
The nature of the iron starvation response in Chlamydia is relatively
uncharacterized because of the likely inefficient method of iron
depletion, which currently relies on the compound deferoxamine
mesylate (DFO). Inefficient induction of the iron starvation response
precludes the identification of iron-regulated genes.
This report evaluated DFO with another iron chelator, 2,2'-bipyridyl
(Bpdl) and presented a systematic comparison of the two across a range
of criteria.
We demonstrate that the membrane permeable Bpdl was superior to DFO in
the inhibition of chlamydia development, the induction of aberrant
morphology, and the induction of an iron starvation transcriptional
response in both host and bacteria.
Furthermore, iron starvation using Bpdl identified the periplasmic
iron-binding protein-encoding ytgA gene as iron-responsive.
Overall, the data present a compelling argument for the use of Bpdl,
rather than DFO, in future iron starvation studies of chlamydia and
other intracellular bacteria.


PMID:21687412

 

*

Offline Dori

  • *****
  • 1443
Re: Oral Chelators
« Reply #6 on: July 10, 2011, 01:19:08 PM »
is Ferriprox really a kind of steriods??


Re: Oral Chelators
« Reply #7 on: August 05, 2011, 09:15:02 AM »
the article i read about combined oral chelation therapy has made me so happy!

God is very kind!

best wsihes to all my friends!!!!!!!!!!!!!!!!!!!!!

*

Offline komal

  • **
  • 50
  • Gender: Female
Re: Oral Chelators
« Reply #8 on: August 07, 2011, 04:27:28 PM »
Hi   Andy,
             Is  it  safe  to  take  asunra  and   desferal    same  day?as   my  haemo  said  no  need  to  worry  take  asunra  along  with  desferal.
Komal

*

Offline Andy Battaglia

  • *****
  • 8793
  • Gender: Male
  • Will thal rule you or will you rule thal?
Re: Oral Chelators
« Reply #9 on: August 07, 2011, 04:45:27 PM »
Hi Komal,

There have been some small but very successful trials using both drugs together, and they were taken on the same day during the trials. I also know several patients who have used this combination and have done very well in quickly lowering their ferritin levels. As long as you get regular monitoring for the effects of Asunra, I would suggest this combination for you, also.
Andy

All we are saying is give thals a chance.

Re: Oral Chelators (Ansunra) for andy
« Reply #10 on: August 11, 2011, 04:58:11 PM »
Andy,
          My daughter is taking asunra for 3 month month now. She is 2.5 years old. Before start of asunra her ferratin was 1350 and after first month of start was 1650 and now its reduced to 372 . But at the same time her SGOT level high at 80 and SGPT at 102 . I am worried if there is any level issue or this is normal . She is taking 300 mg per day and her weight is 11.5 KG. Pls advice asap.


regards
MA

*

Offline Laura

  • ***
  • 155
  • Gender: Female
Re: Oral Chelators
« Reply #11 on: August 11, 2011, 05:35:23 PM »
Hello!

I'm currently under Exjade and Ferriprox. It's been just a month since I started so the only thing I can tell you is that my ferritine did not increase. As you know I'm not the most compliant person with chelators so I think that's the reason why my ferritine is more or less as it was. My purpose for the period before Christmas is to reduce my ferritine by being compliant with the treatment.

I'll tell you more in month time!

Kisses,

Laura.
The most important thing in life is not what you achieve but the fact of fighting for it.

Re: Oral Chelators (asunra) for andy
« Reply #12 on: August 12, 2011, 01:06:04 PM »
Andy,
          My daughter is taking asunra for 3 month month now. She is 2.5 years old. Before start of asunra her ferratin was 1350 and after first month of start was 1650 and now its reduced to 372 . But at the same time her SGOT level high at 80 and SGPT at 102 . I am worried if there is any level issue or this is normal . She is taking 300 mg per day and her weight is 11.5 KG. Pls advice asap.


regards
MA

*

Offline Andy Battaglia

  • *****
  • 8793
  • Gender: Male
  • Will thal rule you or will you rule thal?
Re: Oral Chelators
« Reply #13 on: August 12, 2011, 10:02:18 PM »
Hi MA,

A little trick some people are using to help keep down these levels is splitting the dose in two and taking half in the morn and half in the evening. This also helps reduce nausea. Also, testing early in the day will result in lower scores. The levels your daughter has are not seriously high, but do need to come down a bit, so try splitting the dose, and make sure she is always staying hydrated.
Andy

All we are saying is give thals a chance.

*

Offline Dori

  • *****
  • 1443
Re: Oral Chelators
« Reply #14 on: September 10, 2011, 02:26:50 PM »
Hi Laura, good to hear!

 

SMF spam blocked by CleanTalk