Bloomberg BusinessWeek, Nov 11, 2019 (I)

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(1) James Paton and Chiara Albanese with Luca Casuraghi and Albertina Torsoli, A 1.8 Million Drug Treatment to Treat Sicily's Curse.
https://www.bloomberg.com/news/a ... ase-costs-2-million

Note:
(a)
(i) summary underneath the title in print: A costly targeted gene therapy shows the promise and pitfalls of medical advances
(ii) Print and the online version are identical.
(iii) The southern Italian surname Albanese means Albanian.

Italian-English dictionary:
* albanese (noun masculine or feminine [perhaps depending on the person referred to]): "Albanian [person or language]"
                (adjective masculine or feminine): "Albanian"
https://en.wiktionary.org/wiki/albanese

(b) "She's among an estimated 7,000 Italians, many of them Sicilian, who depend on transfusions to treat beta thalassemia, a genetic disorder that hampers red blood cells' ability to carry oxygen. * * * More than twice as many of its citizens suffer from beta thalassemia as in France, Germany, the UK, and the US combined, Bluebird estimates, and many live on the islands of Sicily and Sardinia. * * * People with beta thalassemia, which can lead to life-threatening anemia, extreme fatigue, and other problems, require transfusions as often as every two weeks. One side effect is excess iron, resulting in possible liver and heart damage if untreated. * * * The blood disorder [thalassemia], related to sickle cell disease, has burdened Sicily for centuries and is common in Africa, Asia, and other regions where malaria historically was also prevalent. Scientists say the gene thrived because it offered protection against the mosquito-borne illness. Carriers [those who inherits one defective gene from one parent and a normal one from the other parent; as opposed to 'patients' who get two defective genes, one from each parent; a carrier has at most mild anemia whereas a patient suffers from moderate to severe anemia, depending what kind of defective gene(s) -- what kind of mutations in that gene -- the patient get] who inherited only one copy of the flaw were more likely to survive and pass on the gene to their children"
(i)
(A) thalassemia (n; New Latin, from [Ancient] Greek [noun feminine] thalassa sea + New Latin -emia [blood, according to various online dictionaries])
https://www.merriam-webster.com/dictionary/thalassemia (pronunciation)

The New Latin -emia (as in leukemia or uremia), in my view, is em blood + ia disease or disorder.
(B) "Both α- and β-thalassemias are often inherited in an autosomal recessive manner. Cases of dominantly inherited α- and β-thalassemias have been reported * * * The thalassemias are classified according to which chain of the hemoglobin molecule is affected. In α-thalassemias, production of the α globin chain is affected, while in β-thalassemia, production of the β globin chain is affected."  en.wikipedia.org for thalassemia.
(ii) Frequent transfusion causes "excess iron." This is because each hemoglobin contains one heme. A heme is composed of a ferrous iron (++m which links with oxygen) and a (flat) porphyrin.
https://en.wikipedia.org/wiki/Heme
("from [Ancient] Greek [noun neuter] haima meaning 'blood' ")

Responsible for the color of blood (bright or dark red -- depending on presence or absence of oxygen), the word porphyrin is from Ancient Greek noun feminine porphyra purple.

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(c) "A novel gene therapy from US-based Bluebird Bio Inc, approved in Europe in June, is set to be rolled out next year following reimbursement negotiations with government health systems. The treatment, called Zynteglo, has a sophisticated mechanism and a lofty price tag—€1.58 million ($1.8 million) per person * * * Bluebird, based in Cambridge, Mass, spent decades developing a way to use a modified virus to transport a functioning version of the gene into a patient's cells to restore production of hemoglobin. That work has finally paid off."
(i) Bluebird's approval in Europe is obtained from European Medicines Agency.
https://en.wikipedia.org/wiki/European_Medicines_Agency
(1995- ; based in Amsterdam)
(ii) Because Bluebird's Zynteglo is currently approved in Europe but not in US, only Bluebird's European website contains mechanism of action.
https://www.zynteglo.eu/mechanism-of-action
(iii) autologous beta-A(T87Q)-globin gene-transduced CD34-positive cells. NCI Drug Dictionary, undated
https://www.cancer.gov/publicati ... cd34-positive-cells
("A preparation of autologous, CD34-positive hematopoietic stem cells (HSCs) transduced ex vivo with the BB305 recombinant replication-defective, self-inactivating lentiviral vector encoding for an engineered form of human beta-globin (hemoglobin-beta, HBB) gene, beta-A-T87Q (b-A-T87Q) where the threonine [an amino acid whose one-letter code is T] at position 87 [in β globin] has been substituted with glutamine [an amino acid whose one-letter code is Q], with potential to restore beta-globin expression and function. Autologous CD34-positive stem cells are isolated from the patient's own bone marrow and the cells are transduced with the lentiviral vector. Upon re-infusion of the b-A-T87Q-globin gene transduced CD34-positive cells back into the patient, these cells express b-A-T87Q-globin, thereby allowing the body to make normal hemoglobin and thus normal, healthy red blood cells. Beta-globin, the beta-chain of the most common form of hemoglobin, is encoded by the HBB gene; mutations in this gene prevent normal beta-globin production and are associated with beta-thalassemia and sickle cell anemia. The b-A-T87Q form of beta-globin has increased antisickling activity compared to the wild type protein")
(A) CD34
https://en.wikipedia.org/wiki/CD34
appears on the cell surface of hematopoietic stem cells, the mother of all lines of blood cells (from red to white to platelets). There are many proteins on cell surface, which is designated 1, 2, 3 and so on.
(B) autologous (adj; from Ancient Greek noun masuline autos self): "derived from the same individual"
(C) transduction
https://www.merriam-webster.com/dictionary/transduction
(D) lentivirus
https://en.wikipedia.org/wiki/Lentivirus
("lente-, Latin [adverb] for 'slow' ")
(E) Antonym of in vivo, Latin adverb and adjective ex vivo means outside a living organism.
(F) The "b-A-T87Q" -- or "bA-T87Q" on some medical literature -- has "b-A" and "bA" that mean "adult beta globin." Why add "adult," considering beta globin gene was activated only after birth?  This I do not know. However, other (lower) vertebrates have more than one beta globin gene, unlike humans (who has one from each parent).
(G) Begre O et al, Gene Therapy of the β-Hemoglobinopathies by Lentiviral Transfer of the βA(T87Q)-Globin Gene. Human Gene Therapy, 27: 148 (2016)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4779296/
("Sickle cell disease (SCD) and β-thalassemia major (β-TM), the latter defined clinically as transfusion-dependent cases regardless of the underlying genotype, are the most common monogenic disorders worldwide with approximately 400,000 affected conceptions or births each year. These disorders fall into two large groups of β-globin gene mutations that result in either abnormal hemoglobin structure (SCD) or massively reduced/absent production of β-globin chains (β-TM). The clinical manifestations of these inherited disorders typically appear several months after birth, when gene expression switches from the fetal γ-globin chain, which forms fetal hemoglobin (HbF), to the adult βA-globin chain forming hemoglobin (HbA).3 Note that adult βA-globin is also simply referred to as β-globin when no confusion with other β-like globin chains is possible") (citations omitted)

This report has superscript that this website (Mitbbs.com) does not support. So you will have to read the report to see where the superscripts are.

(d) "Dozens of gene therapies for a range of devastating illnesses are on their way. These single-dose [ie, one treatment, and that is it] drugs, tailored to each patient, can potentially deliver a lifetime of benefits [potentially, because clinical trial was done in the past several years, so there is no firm prediction how long the treatment will last, though in theory it will last a lifetime]. * * * Regulators predict there could be as many as 20 cell and gene therapy approvals annually by 2025. Novartis AG's Zolgensma, which was approved in the US in May for a childhood illness called spinal muscular atrophy, is priced at $2.1 million. UK-based Orchard Therapeutics Plc is also developing a treatment for beta thalassemia, which afflicts almost 300,000 people globally. Zynteglo could gain approval in the US next year and reach $1 billion in annual sales in 2025.

How It Works. Zolgensma (whose last three letters stands for spinal muscular atrophy), undated
https://www.zolgensma.com/how-zolgensma-works
(transcript of the video: "Let's learn how ZOLGENSMA works to treat SMA. It has two parts⁠—a gene and a vector⁠—and is made in a laboratory by scientists. First, let's focus on the gene. It's a new, working copy of a human SMN gene * * * Now, let's look at the vector. The vector used by ZOLGENSMA is made from a virus called adeno-associated virus 9, or AAV9. This type of virus does not make people sick. To make the vector, the DNA of the virus is removed. With the DNA gone, the fully functional SMN gene is placed inside the vector. * * * But how does ZOLGENSMA work? Once inside the body the vectors deliver new, working copies of SMN genes to the motor neuron cells. ZOLGENSMA sits inside the nucleus of the motor neuron cell and does not become part of the child's DNA [that is the introduced SMN gene does not integrate into host DNA but exists separate inside the nucleus -- perhaps many copies of the gene in one motor neuron]. Then, the new genes tell the motor neuron cells to start making SMN protein")