Tag: gene therapy

Teachable moment in classrooms:

1. cellular basis of life chapter – concept of one gene, one protein
2. cellular basis of life chapter – concept of gene mutation leading to protein malfunction
3. tissue chapter – the basement membrane is a thin layer of tissue in-between epithelium and the underlying connective tissue
4. integumentary system chapter –the integrity of the skin depends on the secure connection of the dermis to the basement membrane

The news item:  Recently the following news item appeared online:

U.S. FDA approves Krystal Biotech’s skin-disorder gene therapy

(Reuters) -The U.S. Food and Drug Administration on Friday approved Krystal Biotech Inc’s first-of-its kind topical gene therapy for patients with a genetic skin disorder, sending its shares up 7% in afternoon trading. Patients with the rare dystrophic epidermolysis bullosa disorder suffer from open wounds, causing skin infections and are at an increased risk of vision loss, scarring and skin cancer.

The article states that the therapy named Vyjuvek healed skin wounds in 65% of dystrophic epidermolysis bullosa patients as opposed to 22% healing rate with placebo treatment. The article also states that about 10,000 people world-wide, and 3000 people in the USA suffer from the disorder.

So, Why Do I Care??  While severe forms of epidermolysis bullosa are life-threatening, moderate forms are devastating to the quality of life, as they it creates painful wounds or blisters on the skin, or in the mouth, and the healing wounds lead to widespread scarring. That makes dressing into clothes, wearing shoes, eating difficult. For dystrophic epidermolysis bullosa patients the promise is the possibility of returning to a normal lifestyle after this new treatment.

Plain English, Please!!!  First, let’s talk about epidermolysis bullosa. This is a group of diseases with the shared symptoms of fragile, easy to break skin and blistering of the skin. The three-layered area of epithelium-basement membrane-dermis is made sturdy by several molecules, and if one is malfunctioning because of a mutation, then fragility of the skin results. The many types of epidermolysis bullosa are caused by a variety of genetic mutations.

Second, let’s talk about the cause of dystrophic epidermolysis bullosa. In this type of the disease the missing component is type VII collagen, the molecule that secures the basement membrane to the dermis. Imagine a large picnic table where the table cover is clamped to the table so the wind wouldn’t blow the cover away. Type VII collagen acts like those clamps securing the dermis (the table) to the table cover (the basement membrane). When the type VII college gene suffers mutations, the resulting type VII collagen protein clamp has a distorted shape, and cannot secure the basement membrane to the dermis, and the skin blisters to form open wounds.

Third, let’s talk about how Vyjuvek treatment works. This treatment is delivering a normal type VII collagen gene to the fibroblast cells of the dermis. The gene is enclosed in an inactivated virus, and the viruses are mixed into a gel, and that gel is applied to the wound surface.  Once that virus enters inside the fibroblast in the person’s dermis, then the normal gene is used to make the type VII collagen protein. With time the newly-made, normal type VII collagen “clamps” will secure the dermis to the basement membrane, and prevent new blistering or breaking of the skin.