6.13 - Cystic Fibrosis & Gene Therapy

Cystic fibrosis, a recessive inherited disorder

• Cystic fibrosis is a genetic disorder of the cell membranes, caused by the mutation of a single gene.
• The faulty protein this gene makes can no longer properly control the movement of salt and water into and out of cells.
• As a result, the body produces a lot of thick, sticky mucus that builds up in:
  • The air passages of the lungs (the bronchioles)
  • The pancreas
• This leads to frequent, serious lung infections and to problems with digesting food.

A recessive allele

• The disorder is caused by a recessive allele, usually written as a lowercase f.
• Because the allele is recessive, a person only has cystic fibrosis if they inherit two copies of it - so an affected person is homozygous recessive (ff).
• A person with just one copy (Ff) does not have the disorder, because the normal dominant allele still works. They are called a carrier and can pass the faulty allele on.
• The recessive allele is fairly common - about 1 person in 25 carries it, so many carriers have no idea they could pass it on.

Inheriting cystic fibrosis

• For a child to be born with cystic fibrosis, both parents must each pass on a recessive allele - so both must be carriers or have the disorder themselves.
• Crossing two carriers (Ff × Ff) gives four equally likely combinations: FF, Ff, Ff and ff.

For any one child, the chances of each outcome are:

Gene therapy for cystic fibrosis

• Gene therapy attempts to treat a genetic disorder by altering a person's genes, replacing or adding a working version of the faulty allele.
• It's being developed as a possible treatment for cystic fibrosis.
• The idea: insert copies of the working, non-mutated allele into the cells lining the lungs, so those cells make the correct protein and the airways produce less thick mucus.
• The treatment can be delivered straight to the lung tissue using an inhaler.

Why it's not yet a reliable cure

• It's hard to get the new alleles into the correct cells and make them work normally to produce the protein.
• Even when it works, the effect doesn't last - the body gradually replaces the treated cells with new ones that still carry the faulty allele, so the treatment has to be repeated.
• It does nothing to stop the disorder being passed on: the alleles in the person's gametes (sperm or egg cells) aren't changed, so any children could still inherit cystic fibrosis.
• Alongside these limitations, there are questions about how far we should go in altering a person's genes.