Hello dear friends
Last week I attended the 11th International Thal Conference that was organized by Dr. El Beshlawy who is the president of the conference and the head of the Egyptian Thalassemia Association (ETA). The conference took place on the 8th and 9th of May and was so interesting.
I attended 25 lectures that were very interesting by so prominent professors. Unfortunately I couldn't take all the notes on each lecture, but the good news is that hopefully I will be able to get a CD that has all the lectures that were said and these presentations were to a great extent very clear
Below I will highlight some important notes that were discussed in the conference * The great thing about this conference was the presence of the two main companies leading the gene therapy trails in the world represented by :
Dr. Susan E. Prockop from Memorial Sloan-Kettering Cancer Center and she is one of Professor Sadelain team for Thalagen from Errant Gene Therapeutics
Dr. Emmanuel Payen from GENETIX Pharmaceuticals that is leading the first gene therapy trails on humans in ParisAs for Dr. Suzan, she explained the details of their protocol (thalagen) and how to implement it, so the lecture was technical, but what is important to us is that last September they started the mobilization phase in three patients (when I post the presentation, it will show the details of those patients) and it went well according to their plan. By next fall, the procedure will be completed and will be able to give results
Their criteria for accepting volunteers were that they should be above 15 years of age, thal major, transfusion dependent with no HLA matched donor, controlled ferritin and good health in general (details will be provided in the presentation), and agree to be monitered once per year for 15 years after the treatment.
Theoretically Dr. Susan claims that they have overcome the complications of other protocols that were studied in the last years by others and the good news too it that gene therapy could be a solution (when available to public) to patients up to 35 years old which is not the case in BMT.
The bad news (FOR ME) is that they are not considering thal intermedia and when asked why is that, she answered me that ''why put them in risk while there could be other options for them''... I totally disagree because sometimes you are faced by ''unsafe '' blood transfusion that could deteriorate the patients' health and putting them in very high risk as well, So the question here '' Should I be completely deteriorated patient so that I can go through this procedure, shouldn't I be in good shape
(This is a concern in countries where there is no safe blood). Also as a patient, do i have the right to choose my treatment?
Anyway, she told me that may be this could be considered for intermedias in the future
As for Dr. Emmanuel Payen, he discussed the details of their first patient who has gone through gene therapy three years ago.
The patient was 18 years when he started the treatment. The protocol was very technical for me to understand, but the result is that the patient is doing very fine and maintaining a HB of 9 - 10. After the treatment that started
32 months, he was transfused heavily and the rate of transfusion decreased until he is fully independent of transfusions from exactly
21 monthsTheir criteria for choosing is the same as Thalagen and they also don't consider thal intermedia
, but they are also in need of funds
PS: Dr. Emmanuel talked about the reason of the activation of gamma genes and therefore producing big percentage of fetal HB after the transfer of the gene, but I really couldn't understand this point, so may be Andy can comment on it when the presentation is uploaded.
*Dr. El Beshlawy too gave a thorough presentation about the NEW trends in the management of thal, discussing all the trends from transfusion, using butyrate, short chain fatty acids, EPO, cytotoxic agents, azacytidine , fetal HB inducers (natural and chemical) and stressed on the usage of magnesium in combination with L-carntine to the patients using hydroxurea.
Dr. El Beshlawy discussed the Egyptian experience in the use of Antisense oligonucliotides (ASOND) in treating patients with IVS1-110 mutation which is the most common in Egypt (40%) in an ex-vivo cell culture. Erythroid differentiation was confirmed with significant increase in total HB and Hb F values in 50% of the cases
*One of the very interesting lectures was of Dr, El Tagui about ‘’Kidney Status in thal’’ this organ is usually forgotten. In summary she discussed that transfused patients are exposed to glomerular dysfunction due to iron overload and non transfused patients are exposed tubular dysfunction due to high oxidative stress due to the chronic anemia and in all cases this means total renal failure.
The important point is that most thal patients and sometimes doctors too, only check serum creatinine levels in addition to urea in blood and may be one or more other functions. According to her study, renal failure can be seen in young patients and creatinine is a deceiving marker because it can fluctuate for different reasons, such as age, pregnancy, protein intake and nutrients,….
According to her study, renal biomarkers that detect renal dysfunction are
1- Urine N-acetyl-beta-D-glucosaminidase (NAG)
2- Cystatin-C (Cys-C),
3- Urinary beta(2)-microglobulin (beta(2)-M)
4- Protein/ Cratinine ratioThe above markers can detect a dysfunction before renal failure and some of these functions show abnormal readings in the presence of normal creatinine. That is why these markers should be checked at least once a year to all patients even the young ones
To be continued……..
Manal