Based on the article “Gene therapy fixes rare skin disease”:
1. Summarize the article by making brief statements defining “who, what, where, when and why.”
Possible student response:
Who: A 7-year-old boy with junctional epidermolysis bullosa and scientists, including Tobias Hirsch and Michele De Luca.
What: Scientists work together and use stem cells and gene therapy to replace 80 percent of the boy’s skin.
Where: Hirsch’s lab is in Germany and De Luca’s is in Italy. The article doesn’t specify where the boy lives or had surgery.
When: Researchers fixed the boy’s skin cells and grew grafts using the cells in September 2015. Skin graft surgeries on the boy occurred in October and November of 2015 and February 2016.
Why: The skin condition is caused by mutations in at least one of three genes needed to express a protein that helps attach the top layer of skin, called the epidermis, to deeper layers.
2. What causes the genetic skin disease this boy has? Be specific.
Possible student response: Patients with this disease have mutations in one of three genes (LAMA3, LAMB3 or LAMC2) that produce parts of the protein laminin 332. Laminin 332 helps to attach the epidermis to deeper layers.
3. Why are children with this disease sometimes referred to as “butterfly” children? What is the frequency and prognosis for patients with this disease in the United States?
Possible student response: Children with this disease are sometimes called “butterfly” children because their skin is as fragile as a butterfly’s wings. The top layer of skin can be easily rubbed off because it is not well attached to deeper layers. Even modest friction or bumping can cause severe blistering, both for external skin (resulting in visible blisters) and for mucus membranes inside the body (making breathing, swallowing and digesting food difficult). About 1 in every 20,000 babies in the United States is born with this disease, and more than 40 percent of those die before adolescence.
4. What treatment did this boy receive prior to the stem cell and gene therapies, and did the treatment work?
Possible student response: He received a skin graft from his father, but his body rejected the transplanted tissue.
5. How was new skin for the boy prepared in a lab?
Possible student response: Researchers took a 4-square-centimeter sample of unblistered skin from the boy’s groin region and grew skin stem cells from that sample. A retrovirus was used to insert a healthy copy of LAMB3 (the gene that is defective in the boy) into the cells, and sheets of the corrected skin cells were grown.
6. How well developed was the gene therapy technique before it was tried on this boy? What was the outcome for the boy?
Possible student response: Researchers had previously grown and replaced only 0.06 square meters of skin, but this patient needed approximately 0.85 square meters, about 14 times as much skin. About 80 percent of his skin seems fully functional, and he still has blistering in some untreated areas. Those affected regions of skin might be replaced with grafts in future surgeries, or cells without the mutation from treated areas on the boy’s body may spread on their own into untreated areas. The boy is back in school and playing soccer.
7. What are two competing theories for how skin cells are naturally replenished?
Possible student response: (1) The skin is populated by a large number of stem cells, each of which can either copy itself or turn into various types of mature skin cells. (2) Only a small number of long-lived stem cells, called holoclones, produce short-lived progenitor cells that then become mature skin cells.
8. How were the boy’s repaired cells monitored?
Possible student response: When the retrovirus added the healthy LAMB3 gene to the lab-cultured cells, it landed in different regions of the DNA sequence in different cells. DNA samples from the boy’s current skin cells can be compared with those from the lab-grown cells to identify which of the boy’s skin cells came from which lab cells.
9. What do the results from tests of the boy’s skin indicate about the two competing theories for how skin cells are naturally replenished?
Possible student response: At first, 91 percent of the boy’s new skin cells were genetically different from holoclone cells, but after four months, only 37 percent of his new skin cells were genetically different from holoclone cells. This indicates that most of his cells were descended from the small number of genetically corrected holoclone cells, and that second theory mentioned in the answer above appears to be a better explanation.
10. What other questions do you still have after reading the article?
Possible student response: What are the similarities and differences between progenitor stem cells and holoclone cells? What other treatments have been given to children with this disease?
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