Lumacaftor prevents it from being recycled so that it makes it to the plasma membrane. The more than 40 percent of patients with CF with other mutations — some quite rare — are not always as lucky. There are over 1, mutations in the CFTR gene that cause CF, and only a minor fraction have been tested for response to the approved drugs.
Still, the researchers are hopeful that they will one day be able to help everyone. Cutting foresees eventually categorizing each patient by theratype, a word he coined to describe groups of patients who are likely to respond to the same therapy because of a common underlying cause of their symptoms.
We can use information generated by experiments in cells to group mutations that affect the same property of CFTR and therefore should respond to the same panel of CFTR drugs. For these, researchers are developing ways to target the mutated gene itself, though there are still many hurdles to overcome. Guggino has worked out a gene therapy system that uses a modified adeno-associated virus AAV to deposit a good version of the CFTR gene inside cells.
The system has proven itself in human airway cells and rodents. Trying a different approach, Liudmila Cebotaru, from the Department of Medicine, devised a novel way to combine gene therapy and protein repair by a mechanism called transcomplementation. They hope to start a clinical trial in the next few years, if all goes well. For the researchers and patients alike, the destination is nothing less than a cure for CF. And though it is still a long way off, there are encouraging signs that we may get there.
Geneticist Ada Hamosh got a call from the neonatal intensive care unit to see a baby with a strange combination of symptoms: He had a brain bleed and almost no nose, two seemingly unrelated traits Hamosh had never seen together before. She knew that she didn't have much time before the hemorrhaging damaged the baby's brain irreparably.
She did a quick search in a database known as Online Mendelian Inheritance in Man. Based on similar reported cases, she learned that what the baby needed was an immediate infusion of vitamin K. Contact us or find a patient care location.
Privacy Statement. Each gene occupies a certain location on a chromosome a thread-like material that is located in the nucleus of every single cell in the body. Chromosomes come in 23 pairs, and each chromosome carries thousands of genes. Each gene has a specific role in determining how a person's body is put together and how it functions.
The role of a gene is determined by its individual DNA code deoxyribonucleic acid, the chemical coding for a gene. DNA is made up of four building blocks called bases. These bases are joined in a specific order for each gene. When a change occurs in the arrangement of the bases, it can cause the gene not to work properly.
A structural gene change which can cause a disease or a birth defect is called a mutation. Genes are inherited in pairs, with one gene inherited from each parent to make the pair. Cystic fibrosis occurs when both genes in the pair have a mutation. A person with cystic fibrosis inherits one CF gene from each parent. Cystic fibrosis is a genetic disorder caused by inheriting a pair of genes that are mutated or not working properly.
Everyone inherits two copies of the CFTR cystic fibrosis transmembrane conductance regulator gene. When the cell tries to read its RNA copy of the instructions, it no longer can tell where to begin and end reading. As a result, the cell will either leave in some irrelevant letters, or remove some relevant ones. When the cell tries to follow the RNA instructions containing the irrelevant letters, or missing relevant ones, it will be unable to build a correct CFTR protein.
The CFTR protein is made up of 1, amino acids. It has to be the right shape to transport chloride. When a mutation causes an amino acid to be deleted or an incorrect amino acid to be added, the CFTR protein cannot form its correct 3-D shape and function properly.
These mutations are considered to be protein processing mutations. The most common CF mutation, Fdel, is primarily considered to be a processing mutation. The cell recognizes that the protein isn't the right shape and disposes of it. Although this drug combination is not a perfect fix, it helps the mutant CFTR protein to move some chloride.
This movement of chloride reduces the symptoms of CF. Watch the webcast starting at to learn more about CF protein processing mutations and how drugs such as CFTR modulators can help a person with one of these mutations.
Researchers are working on more effective drugs that can fold the protein into a more normal shape, move more chloride out of the cell, and reduce symptoms even further. In addition to Fdel, missense mutations can sometimes cause processing problems and therefore can be considered processing mutations in those cases. The CFTR protein is shaped like a tunnel, or channel, with a gate.
The cell can open the gate when chloride needs to flow through the channel. Otherwise, the gate stays closed. Gating mutations lock the gate in the closed position so that chloride cannot get through.
This enables chloride to move through the channel and reduces the symptoms of CF. Watch the webcast starting at to learn more about CF gating mutations and how drugs, such as CFTR modulators, can help a person with one of these mutations. Sometimes, a change in one of the amino acids of CFTR means that even though the protein makes the right 3-D shape, it doesn't function as well as it should. In order for CFTR to work correctly, chloride has to be able to move quickly and smoothly through the protein's channel.
Some mutations change the shape of the inside of the channel so that chloride cannot move through as easily as it should.
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