"Thalassemia was emotionally taxing on my family, but we adapted" - Patient profile of Aaron Cheng,

My name is Aaron Cheng, and I’ve just completed my first semester of college at Harvard

University.

I don’t remember when I was diagnosed with beta thalassemia major, which is also known as Cooley’s Anemia, but my parents tell me it was when I was around one year old.  We were visiting Taiwan, and my mother and father noticed specks of blood in my diaper.  Soon afterward, doctors told my parents that I had Cooley’s anemia. 

I’ve been under treatment for as long as I can remember. From when I was an infant to when I became a middle-schooler, I took Desferal infusions four times a week.  The Desferal treatment would last for about eight hours every night, from when I went to sleep to when I woke up. Treatment now is definitely a lot more convenient: instead of having injections every night, I use the oral chelator Exjade every night, so my schedule is a lot more flexible now.  I am so thankful that treatment is becoming a lot more convenient for Cooley’s anemia patients; as a college student, I find taking a pill a lot easier than injecting a drug for eight hours every night. 

I remember that as a child thalassemia was a lot more painful for my family and me than it is now.  The most difficult aspect for me was feeling different from my friends, since I would be noticeably absent from school when I visited the doctor.  I think the hardest part for my parents was trying to deal with the disease and make sure I had a balanced life.  Thalassemia was emotionally taxing on my family in the early part of my life, but we quickly adapted to the new lifestyle, and now it feels like thalassemia is nothing more than an easily managed inconvenience. 

Besides keeping up with my medicine every day, I don’t think thalassemia greatly impacts my life.  I am still able to lead a perfectly normal college life and try new things every day.  Perhaps thalassemia might make me more tired than the average person when it gets close to a transfusion day, but I find college exciting enough that any physical effect that thalassemia has on me is usually barely noticeable. 

My family first found out about the Cooley’s Anemia Foundation when my doctor introduced my father to the association.  From then on, my family has been very involved, and I attend conferences as often as I can.  It has offered a great community through which I can share my experiences and learn from others who have thalassemia as well.  I find the Foundation to be an extremely helpful forum for patients and family; my family and I have met many friends and gotten a lot of help coping with thalassemia through the CAF.  

I decided to attend Harvard primarily because it had always been my dream school; I love the Boston area and thought it would be a great experience to live on the East Coast and learn in such an academically-driven community.  Furthermore, the Boston area is very convenient, and I am able to go to the Boston Children’s Hospital quickly every three weeks for my transfusions. 

It was such a surprise for me when I was accepted to Harvard and I knew right when I found out that I couldn’t turn this opportunity down.  It has been a great experience for me so far; I am involved in the Harvard Crimson (Cambridge’s daily newspaper), and the Harvard Square Homeless Shelter where I volunteer.  I’ve enjoyed all of my classes so far and learned so much.  Right now I am unsure what I will study for a major, but I am strongly considering molecular/cellular biology, neurobiology, or applied math with a focus on biology.  I am keeping my career options open until I find out in the coming years what I enjoy most.  

Adjusting to a new climate away from my family was easier than I imagined, partly because Harvard keeps me so busy and also because the people there are so friendly that it took a very short time for me to make a lot of new friends.  The weather is noticeably colder than sunny Southern California, but I’ve been having a lot of fun experiencing the new climate. 

The adjustment to Boston Children’s Hospital has been exceptionally smooth; every three weeks I go to the nearby clinic to get my blood drawn, then on the Saturday after I take a 20-minute bus ride to Boston for my transfusion. 

The future looks bright, and I’m looking forward to learning so much more and having the opportunity to give back to the community!

 

New gene transfer technique can treat beta-thalassemia, sickle cell anemia

A team of researchers led by scientists at Weill Cornell Medical College has designed what appears to be a powerful gene therapy strategy that can treat both beta-thalassemia disease and sickle cell anemia. They have also developed a test to predict patient response before treatment.
This study's findings, published in PLoS ONE, represents a new approach to treating these related, and serious, red blood cells disorders, say the investigators.
"This gene therapy technique has the potential to cure many patients, especially if we prescreen them to predict their response using just a few of their cells in a test tube," says the study's lead investigator, Dr. Stefano Rivella, Ph.D., an associate professor of genetic medicine at Weill Cornell Medical College. He led a team of 17 researchers in three countries.
Dr. Rivella says this is the first time investigators have been able to correlate the outcome of transferring a healthy beta-globin gene into diseased cells with increased production of normal hemoglobin -- which has long been a barrier to effective treatment of these disease.
So far, only one patient in France has been treated with gene therapy for beta thalassemia, and Dr. Rivella and his colleagues believe the new treatment they developed will be a significant improvement. No known patient has received gene therapy yet to treat sickle cell anemia.
A Fresh Approach to Gene Therapy
Beta-thalassemia is an inherited disease caused by defects in the beta-globin gene. This gene produces an essential part of the hemoglobin protein, which, in the form of red blood cells, carries life-sustaining oxygen throughout the body.
The new gene transfer technique developed by Dr. Rivella and his colleagues ensures that the beta-globin gene that is delivered will be active, and that it will also provide more curative beta-globin protein. "Since the defect in thalassemia is lack of production of beta-globin protein in red blood cells, this is very important," Dr. Rivella says.
The researchers achieved this advance by hooking an "ankyrin insulator" to the beta-globin gene that is carried by a lentivirus vector. During the gene transfer, this vector would be inserted into bone marrow stem cells taken from patients, and then delivered back via a bone marrow transplant. The stem cells would then produce healthy beta-globin protein and hemoglobin.

This ankyrin insulator achieves two goals. First, it protects delivery of the normal beta-globin gene. "In many gene therapy applications, a curative gene is introduced into the cells of patients in an indiscriminate fashion," Dr. Rivella explains. "The gene lands randomly in the genome of the patient, but where it lands is very important because not all regions of the genome are the same." For example, some therapeutic genes may land in an area of the genome that is normally silenced -- meaning the genes in this area are not expressed. "The role of ankyrin insulator is to create an active area in the genome where the new gene can work efficiently no matter where it lands," Dr. Rivella says. He adds that the small insulator used in his vector should eliminate the kind of side effects seen in the French patient treated with beta-thalassemia gene therapy.
The research team also discovered that the insulator increases the efficiency by which the beta-globin gene is transcribed during the process of making the red blood cells. "We found the gene is integrated into cells which have not yet begun to make red blood cells, and when they do, the beta-globin gene is activated," Dr. Rivella says. "We showed that if the insulator is present, activation of the curative gene is more efficient. This provides more curative protein to red blood cells."

The study further provides evidence that the vector had different rates of efficiency depending on the beta-thalassemia mutation it was used in -- thus providing the basis for a predictive test in patients. The investigators tested 19 different beta-thalassemia samples comprising the two types commonly found in patients -- "beta-zero" cells that do not produce any beta-globin (forcing patients to receive blood transfusions throughout life), and "beta-plus" cells that produce suboptimal levels of hemoglobin. On average, they found that one copy of the vector in beta-zero cells produced 55 percent of the adult hemoglobin seen in normal individuals. Beta-plus cells, after treatment, produced hemoglobin comparable to a healthy individual, and were thus cured.
"The variable nature of the beta-thalassemia mutations suggests that some patients would be better candidates for gene therapy than others, and that success of gene therapy depends on the ability of a specific vector to make hemoglobin," Dr. Rivella says. "This is something we can test in advance using a little bit of a patient's blood -- which is quite extraordinary."
The issue in sickle cell anemia is very different, Dr. Rivella says. The hemoglobin protein is made in the right quantities, but it is not normal -- the red cell is shaped like a sickle and is abnormal in function. "One of the problem in gene therapy of sickle cell anemia is to add a new gene without increasing too much the total amount of protein, both normal and sickle. This would cause other problems," he says.
By treating eight cell specimens taken from sickle cell anemia patients, the investigators discovered that attaching the ankyrin insulator to a normal beta-globin gene increases the amount of normal beta globin protein while reducing the quantity of sickled protein. "The total amount of protein stays the same, which is very important," says first author Dr. Laura Breda, pediatric research associate at Weill Cornell Medical College.
The researchers say that their advances will likely make a substantial impact on a number of fields, including gene regulation and transfer and the design of gene therapy trials. "This study represents a fresh departure from previously published work in the field of gene therapy," Dr. Rivella says.

Source: Weill Cornell Medical College