Name: Airena Rain Tayum Tampos
🦋
Gene Therapy for “Butterfly Children”
Videos of the “butterfly children” are difficult to watch. The name comes from the
delicate skin of people who have epidermolysis bullosa, which is reminiscent of the
fragility of a butterfly’s wings. The slightest touch causes painful blisters and peeling
skin. Parents can be carriers of Recessive dystrophic epidermolysis bullosa
(RDEB) without having any of the effects. RDEB affects about 1 in every 20,000 births
in the United States.
Parents of RDEB children provide intensive care for their children, which includes daily
full body bandage changes and use of antibiotics and antiseptics. These bandages
are made of special polymers that have low adhesion so they don’t tear the skin if a
parent pulls a bandage off.
The daily bandage changes, pricking of blisters, and removing flaky skin aren’t all the
requirements. Bathing can take hours. Complications include anemia, malnutrition from
mouth and esophagus sores that make eating nearly impossible and skin cancer.
Scarring of skin can cause the fingers and toes to fuse together creating “mitten”
deformities. Patients may need surgical procedures to cut fingers free. Over time
rigid joints and deformities emerge as the damaged skin shrinks and tightens muscles
and tendons, causing contractures, which further reduces mobility.
In healthy skin, anchoring fibrils made mostly of Type VII collagen protein knit the thin
epidermis to the dermis below. In RDEB, any of 200 mutations prevent the formation of
the fibrils. Gene therapy may offer hope for repairing these mutations.
Gene therapy uses viruses to deliver functional COL7A1 genes, which encode the
collagen, into cells taken from patients and growing outside the body (“ex vivo”), and
then injects the doctored self-cells into selected areas of skin.
RDEB gene therapy is localized, and would coincide with patients’ routine
hospitalizations, treating one skin area at a time. In younger children with RDEB,
wounds start emerging on the body before they become immobile with contractures by
their early teens. One of the clinical strategies is to treat earlier and prevent these
small areas from becoming larger areas. Focusing on certain areas, like the
fingers,may better improve quality of life.
Fibrocell, a cell and gene therapy company, is targeting fibroblasts, and described
the effect of their product on five wounds treated in three adults. At the 12-week mark
four of the wounds were greater than or equal to 70% healed and type VII collagen
produced, although anchoring fibrils were not yet observed.
Date: March 11, 2022
1. What part of the body is affected by epidermolysis bullosa?
It develops in the outer layer of skin and mainly affects the palms and the feet.
2. How is the disease currently treated?
Antidepressants medicine used to treat epilepsy, and acetaminophen can be helpful.
If the pain is severe, medicine like fentanyl, morphine, or ketamine can be
prescribed. Before bathing and wound care, it may be necessary to give pain
medication to someone with EB. Doctors can change a person's genetic makeup
through gene therapy. Viruses are used to transmit functional genes into cells
extracted from patients and grown outside the body, and the doctored self-cells are
then injected into specific parts of the skin.
3. What is a “contracture?”
A permanent tightening of the muscles, tendons, skin, and nearby tissues that
causes the joints to shorten and become very stiff. This prevents normal movement
of a joint or other body part. Over time rigid joints and deformities emerge as the
damaged skin shrinks and tightens muscles and tendons causing contractures.
4. Describe the role of Type VII collagen in skin?
Type VII collagen protein plays an essential role in knitting the thin epidermis to the
dermis below. It simply strengthens and stabilizes the skin.
5. Use the graphic on the next page for a more detailed examination of how the
process works. What is the source of the modified fibroblasts?
From the epithelial cell of the patient.
How is the correct gene added to the cells?
Gene therapy uses viruses to deliver functional COL7A1 genes, which encode
the collagen, into cells taken from patients and growing outside the body (“ex
vivo”), and then injects the doctored self-cells into selected areas of skin.
How are the fibroblasts modified?
The patient is given amplified fibroblast cells to administer localized therapy that is
compatible with the patient's biology.
It delivers localized therapy that is compatible with the patient’s unique biology. It
is also transduced with LVMyoD alone or in combination with LVCx43GFP and
Name: Airena Rain Tayum Tampos Date: March 11, 2022

plated onto the feeder layer at 2×105 cells per coverslip. Growth medium was
changed to differentiation medium after 2 to 3 days and subsequently changed
every third day.

How the modified cells are then used to treat EB?

The vector is delivered to the fibroblast cell culture, which transfers the
therapeutic gene to the patient's cells where it expresses the specific protein

6. Consider the underlined sentence in the second to last paragraph. What does this
mean for the success of the treatment?

The underlined sentence in the second to last paragraph means that the success of
the treatment is still under observation.
Anchoring fibrils are sticky suprastructures that keep the epidermal basement
membrane connected to the dermal extracellular matrix. The fibrils are polymers of
collagen VII which is the main structural fibril component although they may also
contain other proteins. Remarkable progress has been made in the last few years in
understanding the functions of skin basement membrane components including the
anchoring fibrils. In analogy to heritable disorders of other collagen genes,
predictable phenotypes of COL7A1 mutations causing premature termination codons
or dominant negative interference have been observed. However, collagen VII seems
to represent a remarkable exception among collagens in that many mutations,
including heterozygous glycine substitutions and deletions, lead to minimal
phenotypes or to no phenotype at all.
Therefore, not only is the definition of the mutation(s) important, but also cell biology,
protein chemical, and suprastructural analyses of the altered molecules provide
unique insights into the molecular pathomechanisms underpinning illness.
Name: Airena Rain Tayum Tampos Date: March 11, 2022

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