FerroKin - latest oral chelator in phase 2 of trials

FerroKin may soon be an alternate choice of chelation.  The more choices we have available the better it is for the thalassemia population.  With these oral chelators it is now possible to keep iron levels closer to normal.  As noted earlier, desferal is not recommended when iron levels are below 1000 - but these oral chelators (sometimes a combination thereof) can help achieve much lower iron levels than previously thought possible.  As iron is a main culprit, as a free radical, in destroying healthy tissues and organs - maintaining near normal levels of iron may be the answer to longer and healthier lives for those suffering from thalassemia and related blood disorders. 

Sharmin

http://cooleysanemia.org/index.php?option=com_content&view=article&id=346:ferrokin-opens-phase-2-trial-of-oral-chelator&catid=1:latest-news

Sharmin,

I am not aware of this: why is desferal not recommended for ferritin levels under 1000? I have not heard that before. In fact, a lot of thals here use desferal under 1000.

Lena

I have also previously heard that desferal should be stopped when ferritin is below 1000. This was formerly a cautious practice that was used in hopes of avoiding damage to vision and hearing. However, actual usage has led to instructions using this type of wording.

If ferritin values fall below 1000 ng/mL, the risk of Desferal toxicity
increases; it is important to monitor these patients particularly carefully and perhaps to consider lowering the total weekly dose...

Desferal treatment is indicated in any of the following situations:
any symptomatic patient with a serum iron level greater than 300 to 350 micrograms/dL
regardless of the total iron binding capacity (TIBC). It has also been suggested that a conservative
approach without Desferal therapy or challenge should be considered when serum iron levels are
in the 300 to 500 micrograms/dL range in asymptomatic patients, as well as in those with selflimited,
non-bloody emesis or diarrhoea without other symptoms.

The following suggested criteria are believed to represent appropriate requirements for cessation of
Desferal. Chelation therapy should be continued until all of the following criteria are satisfied:
• the patient must be free of signs or symptoms of systemic iron poisoning (e.g., no acidosis, no
worsening hepatotoxicity),
• ideally, a corrected serum iron level should be normal or low (when iron level falls below 100
micrograms/dL). Given that laboratories cannot measure serum iron concentrations accurately in
the presence of Desferal, it is acceptable to discontinue Desferal when all other criteria are met if
the measured serum iron concentration is not elevated,
• repeat abdominal radiograph test should be obtained in patients who initially demonstrated
multiple radiopacities to ensure they have disappeared before Desferal is discontinued because
they serve as a marker for continued iron absorption,
• if the patient initially developed vin-rosé coloured urine with Desferal therapy, it seems reasonable
that urine colour should return to normal before halting Desferal (absence of vin-rosé urine is not
sufficient by itself to indicate discontinuation of Desferal).

So, as the case with all chelators, regular observation and testing for ferritin should be the keys to determining the correct dose and whether or not any dose is required. When close monitoring is readily available, ferritin levels of 100 or lower can be the goal. For those without access to regular monitoring, I would highly recommend that desferal not be used when ferritin is below 300-350.

Dr. Vichinsky had told me about this chelator.  Along with auditory and visual disturbances, doctors have also warned us that desferal can be quite devastating to the bones.  It can cause changes in the frame of the body and contribute to osteoporosis.  When lil A was younger, he would experience ringing in the ears if his ferritin was below 1000 - while on desferal.  For a very short time his very high range hearing was affected.  Once desferal was stopped his hearing completely returned to normal because the toxicity was cleared.  For now we are happy with exjade as his iron levels have remained low despite his increased transfusion frequency with the antibody issues. 

Hopefully this latest chelator will be a lifesaver for those who have not had success with the currently available chelators. 

Sharmin

The more the merrier I sometimes wish that these chelators were available 20-30 years ago,so senior thals would have been in much better condition,and my aunt might not have lost her first born daughter.

Me too, Zaini!

Lena

And the more we hear about patients having problems with Exjade, the more we see how much new chelators are needed.

In what way do these chelators differ, is it only the active component or the mechanism of how iron leaves the body or is it the target to reach a drug with the least side effects???

manal

Of the three well known chelating drugs, only deferiprone (L1, Ferrirpox, kelfer) is a small enough molecule to penetrate certain areas of the body and it also does a much better job accessing heart iron than the other chelators. These natural substance chelators can all get everywhere in your body. IP6 is already found in every cell in the body. Because they literally do penetrate all tissue, they can chelate where other chelators do little or nothing. This is making a big difference for those using these substances, even if they don't realize it.

I would actually like to see a controlled study of thalassemics who are given IP6 from birth, to see if there is any difference in pituitary scans. The antioxidant effect may be more important than its chelating effect in young children, as it is the oxidative stresses that are the most likely culprit in shrinkage of the pituitary, even in the presence of a low iron load. The pituitary gland eventually disappears in thals even when iron load has never been an apparent issue. When you look at what is caused by thalassemia itself and the unmatched globin chains created, the bad hemoglobin produced and the irregular red blood cells, there is much more than iron to combat. We should also be looking at fighting oxidation, oxygen depletion and nitric oxide depletion. If I was asked what I would give a newborn thal for supplements, the list would include vitamins D and E, IP6, some version of L-carnitine with alpha lipoic acid, folic acid and magnesium drops. Why not fight ALL of the problems of thal from day one, instead of waiting until iron is an issue before anything is done? Iron is only one of the battles. Oxidation will cause tremendous health issues if not confronted.