b.New methods—monitoring of liver iron overload by SQUID:

• Superconducting QUantum Interference Device (SQUID) has been recently introduced as an integral part of thalassemia care in few centers worldwide. The SQUID allows the thalassemia team to monitor iron concentration in the livers of patients and gives them a reliable tool to help adjust medication in order to avoid serious complications [6].

**17**

*Updates in Thalassemia*

in the field are detected [6].

**1.2 Updates in treatment**

*Advantages and disadvantages of SQUID.*

*1.2.1 Gene therapy*

**Table 1.**

*1.2.2 Gene editing*

*1.2.3 Targeting ineffective erythropoiesis*

*DOI: http://dx.doi.org/10.5772/intechopen.92414*

**Mechanism of action of SQUID:**

**Advantages and disadvantages of SQUID:**

SQUID has high-power magnetic field. Iron interferes with the field and changes

High cost

Highly specialized: needs dedicated technician

May underestimate LIC levels

The first obstacle against gene therapy was the extremely complex regulation of the globin genes. The second and equally important obstacle has been the lack of an optimal vector for gene transfer into quiescent hematopoietic stem cells (HSC) [7]. The first successful gene therapy for β-thalassemia major was in 2007. The process is as follow: autologous HSCs are harvested from the patient and then genetically modified with a lentiviral vector expressing a normal globin gene. After the patient has undergone appropriate conditioning therapy to destroy existing

Two large clinical trials have been recently conducted. The first one was entitled

"ß-Thalassemia Major with Autologous CD34+ Hematopoietic Progenitor Cells Transduced with TNS9.3.55 a Lentiviral Vector Encoding the Normal Human ß-Globin Gene." This trial was sponsored by Memorial Sloan Kettering Cancer Center. The second one was entitled "A Study Evaluating the Efficacy and Safety of the LentiGlobin® BB305 Drug Product in Subjects with Transfusion-Dependent β-Thalassemia, who do Not Have a β0/β0 Genotype." It was sponsored by bluebird

A newer approach employs genome editing techniques, such as transcription activator-like effectors nucleases (TALEN), zinc finger nucleases (ZFN), or the

system. They replace the target single-mutation sites with the correct sequence, restoring the functional gene configuration. Producing a sufficiently large number of

corrected genes is the major challenge with this new approach (**Figure 3**) [7].

A large number of preclinical and early clinical studies investigating erythropoiesis modulators are currently studied. These modulators include

clustered regularly interspaced short palindromic repeats (CRISPR) with Cas9 nuclease

defective HSCs, the modified HSCTs are reintroduced to the patient [8].

bio. Expected success awaits these clinical trials (**Figure 2**) [9].

Advantages and disadvantages of SQUID are listed in **Table 1** [6].

**Advantages Disadvantages** Linear correlation with LIC assessed by liver biopsy Indirect measure of LIC May be repeated frequently Limited availability

**Figure 1.** *Technical steps of PGD [2].*
