Inducing Fetal Hemoglobin Production in Beta Thalassemia

One of the most intriguing fields of research into a cure for thalassemia is turning on genes so that the body will produce hemoglobin on its own. eliminating the need for transfusions and all the related problems. This is already being done with chemicals such as hydroxyurea and arginine butyrate, in thalassemia intermedia. Research suggests that there may be other chemicals that both work better and  are more tolerable. However, development is being hindered by the costs of drug resreach and development.

I found an excelent analysis of this topic at

http://www.asheducationbook.org/cgi/content/full/2005/1/38

The ß thalassemias are one of a few medical conditions in which reactivation of a gene product that is expressed during fetal life can functionally replace a deficiency of essential proteins expressed at a later developmental stage...In clinical trials, three classes of therapeutics have demonstrated proof-of-principle of this approach by raising total hemoglobin levels...New oral therapeutic candidates, which stimulate both fetal globin gene expression and erythropoiesis...now make this gene-reactivation approach feasible to produce transfusion independence in many patients. Development of the candidate therapeutics is hindered largely by costs of drug development for an orphan patient population...Major obstacles to development of HbF-inducing agents for thalassemia include: 1) costs of new drug development, including the challenges of pharmaceutical companies weighing the potential market and academic investigators securing financing for drug development; and 2) perceptions regarding the ultimate efficacy (and competitiveness) of this therapeutic approach compared to other approaches. For example, many thalassemia patients are managed with blood transfusions and iron chelators, and the oral chelators are demonstrating therapeutic effects. Therefore, only a fraction of the thalassemia population might initially utilize a HbF-inducing type of therapeutic, even though such drugs would improve the underlying condition...

Summary

The ß thalassemia syndromes are among the few molecularly defined conditions in which an endogenous fetal gene can functionally replace a defective adult gene. Several candidate therapeutics have demonstrated proof-of-principle in these disorders by inducing fetal globin expression and subsequently raising hemoglobin levels in ß thalassemia patients. The magnitude of responses to individual agents is similar to those induced by rhu-EPO in anemic conditions with normal red cell survival, and additive responses occur with drug combinations. New oral candidate therapeutic agents, which both induce fetal globin gene expression and stimulate erythropoiesis, and combinations of therapeutic agents with complementary molecular actions, now make this gene-reactivation approach feasible for many patients. Development of these agents is now hindered largely by costs.

I am curious as to whether patients agree with this quote

... many thalassemia patients are managed with blood transfusions and iron chelators, and the oral chelators are demonstrating therapeutic effects. Therefore, only a fraction of the thalassemia population might initially utilize a HbF-inducing type of therapeutic, even though such drugs would improve the underlying condition

Do you feel this way or would you be willing to try a drug that might increase your Hb to the point where transfusions are no longer needed, or do you feel the way your thal is managed through transfusions and chelation is the tried and true method and you wouldn't be willing to take the chance on an alternative approach?

I'll buy anything as long as it doesn't involve any needles!

O.k I can be a little flexible in that. A shot instead of the hours long TransX will do just fine too as long as it is monthly or more apart.

And as a last resort....

ANYTHING no matter how extensive it is (Such as BMT or CBT) as long as it cures me once and for all.

Andy, where do I sign up for being a lab-rat in this process ?

Take care, Peace!

HI ANDY AND SAJID.

PLEASE DONT LAUGH AT ME, BUT WHAT IS THIS LINK SAYING? THAT THERE CAN/WILL BE A POSSIBLE CURE FOR THAL MAJOR, BY INTRODUCING ORAL MEDS?
I KNOW THEY ARE PROMISING IN INTERMEDIA PTS,BUT WHAT ABOUT MAJORS?
ALSO, IN YOUR OPINIONS,(AND EXPERIENCE) DO YOU THINK THERE WILL BE A CURE IN OUR LIFETIME?

CHRISTINE :hug

Basically this article says that this is already proven that it will work, but that more than one chemical is needed because no chemical works for all thals. More research needs to be done but as the article hinted quite loudly,

Development of the candidate therapeutics is hindered largely by costs of drug development for an orphan patient population.

The patient population isn't perceived as being large enough to justify the expense of research and development of these drugs. These researchers seem sure that this will work for all beta thals, intermedia or major.

Well, if we go beyond the US, we see that the patient population is quite large enough to justify this research. But how do we get funding for it? How do we get thal the notice that things like Aids get? This is a real challenge and it may take novel approaches to gain the attention needed. Face it. Thal is mostly a problem of the poor in countries like India and Thailand where tens of thousands of majors live...and die. We don't have a world that cares enough about the plight of poor non-whites. It is so sad but also so true. If there were 10,000 babies born in the US with thal every year, it would be getting all the attention it needs. But in India, the resources don't exist so the research doesn't happen. We need a world stage. We need attention if these things within our grasp are ever to be made a reality. Even the gene trials have been slow to come because of money.

I do believe a cure for thal, and maybe more than one approach is on the horizon, but it will take money and that will take thal being noticed. We are doing our part in our global village that is this group (thanks for the term, Miaki  ) but can we honestly say that the international organizations are doing their part? TIF, exactly what is it that you do other than arrange conferences in exotic locales? Where is the day to day help for thals that is found in the Cooley's Anemia Foundation in the US? And TIF, does it bother you that more than one thal active in the orgs has told me that I have single handedly done more for thals than all of TIF??? I would be very embarrassed if I was running TIF. If I, a single person with no financial resources can find ways to help thals all over the world, then why can't TIF do a better job???

We can't sit and wait to be noticed. It won't happen. We have to make noise if thal is going to get on the radar of those who can make things happen. TIF isn't accomplishing this so maybe t's time we look for other ways to make it happen. We live in the media age and savvy people will find ways to be noticed. Let's make it happen.

please,please tell me what we can do to raise hell and make ourselves heard! lol i wrote oprah last week (and suprise,suprise,havent heard back).
should we contact our senators,govenors,congressmen? start a global petition?
c'mon people! there are some brilliant minds on this forum, that could make a change, if we just figure out how!
WHAT WILL IT TAKE TO RAISE AWARENESS? HOW CAN WE HELP FUND THE RESEARCH FOR A CURE?? just tell me what I can do to help, and im there!

christine

WHAT IS TIF?

Thalassemia International Federation
http://www.thalassaemia.org.cy/

An organization that should be doing far more for patients than it does...in my opinion.

hello Christine.
In reading all your recent postings I can amphatise with your predicament .I do acknowledge that you want to do your part to stop or prevent the disorders that affect lots of lives around the world.

1. I would suggest that you take time to breathe and think what is your priority right now.
    Lauryn needs all your attention and suport most of all.

2.Learn to ignore the negative and very damaging remarks about your choice. You and you alone knows what is best for your family.No one has the right to vilify you.

3.Assist your daughter in getting the best medical care she needs right now and continuity of it.
Maybe you need to build up strength from knowing that there are lots of young adult here that was once a  baby like Lauryns and they have made it up to now ,and they are achieving thier goals dispite of thier difficulties.

5.We all need to believe that there will be a cure for thal,this ,will able, all of us to move forward.
6.Then, when your daughter is stabilized,you will be in a better position to think clearly and assist in finding a solution,for all other sufferers.
Please dont get cross with me I'm only trying to put the situation into prospective ,in order that you can move forwards ,I wouldn't want to see you loosing time jutifying as to why you made your choice in your life.
Good luck you can only do the best you can.
regards Kathy

We can't sit and wait to be noticed. It won't happen. We have to make noise if thal is going to get on the radar of those who can make things happen. TIF isn't accomplishing this so maybe t's time we look for other ways to make it happen. We live in the media age and savvy people will find ways to be noticed. Let's make it happen.

Way to go Andy!

We definitely need to move up from this forum where someone has to come and find us; to something that can make our voice heard mandatory globally.

Guess what? All the bad things in the world is getting all the global attention which should not happen in the first place while important issues aren't being addressed at all. Maybe we need to play bad too? :evilplan

Naaaah! We can't do that! But we CAN access the path which these baddies follow to get noticed. I'm talking about serious T.V and paper coverage.

Christine you did a good thing to mail Oprah. I would however suggest to mail the news channels (shows) that Thal. needs to be addressed globally and there is a cure for Thal. which is only possible if everyone digs in like they are doing for HIV and Hepatitis.

This is something that TIF or other Thal. associations should do! I guess it's time we make our own Thal. association with an array of global volunteers to access their local media.

I just hope my ranting comes true one day!

Take care, Peace!

Sajid,

Its officially done.I took your advice and I wrote every news station in Phoenix regarding Thal.and raising awareness.
I understand I should bide my time and focus on Lauryn, but since I cant do anything to help her at THIS PARTICULAR MOMENT, I am using my time to spread the word. I will not sit back and do nothing if I can help it. Who knows, maybe being a P.I.T.A. will get Thal some recognition for once.
If you have any other suggestions,please let me know. I dont mind, doing all of the dirty work :evilplan!
lol, tell me who to write, and ill take it from there!
I promised myself and Lauryn I will do EVERYTHING I can, to help Thals and their families.There's no better time to start than RIGHT NOW!
christine

Hi sajid and everyone.

Sajid
Good on you for trying, lets wait for a good outcome.A thousand miles walk commence with one step.
the word in my posting to christine was empathy  and justify not what I wrote.
  I would like to thank-you all for the respect you showed toward me,that is because my grammar is appauling and I don't edit my writting.I know my spelling is not good at times.Never once has anybody corected me.
You are all very kind and on my list you are all number one
Kathy

There's a group at NIH which is conducting a study on affect of raising Hb-F in thals. I participated in the study. They need more volunteers. If you are interested then please check a thread on this study in the announcement section.

Hydroxyurea treatment is exercised more in India (and in other countries) than in US.  I think earlier Hydroxyurea treatment was approved for sickle cell patients *only* and not for thals in US. Don't know if it is still the case.

--Hallu

kathy... you are so cute. i write like crap,and english was my major in high school.lol i dont have an excuse.

hallu, they are using hydroxyurea in majors? what kind of results did YOU have in the study? where is the study being conducted?
my 2 year old cousin,whos an intermedia,is on hydroxyurea and her hgb levels are increasing. i hope it continues.

Christine,

what kind of results did YOU have in the study? where is the study being conducted?
my 2 year old cousin,whos an intermedia,is on hydroxyurea and her hgb levels are increasing. i hope it continues.

This study is held at NIH, Maryland US and is not aimed at providing treatment. The scope of participation was to just give blood samples to the team.
I participated in the study and they shared few blood reports(CBC, electrophoeresis etc) with me. Thats it! But I talked to the folks and they told me that this study deals with studying affect of increased Hb-F in thals.

I didn't know that in US Hydroxyurea treatment is approved for thals. Thanks for providing the info.

--Hallu

hi guys.

i just wanted to let you know that we donated Lauryns cord blood to research. so who knows???
love,
christine