In introducing our speaker and his guest, Paul Mikkelson wished Phil Ferrari continuing recovery and welcomed the Simsbury Club's president-elect, Doug Morehouse. Paul introduced Melanie DiNicola, the senior development director of the Connecticut Chapter of the Cystic Fibrosis Foundation (CFF). She has been doing development for CFF since her daughter Tiffany was diagnosed with cystic fibrosis (CF) in 2005.
Melanie DiNicola, who grew up with 7 brothers, shared her personal experience with cystic fibrosis (CF). Her daughter Tiffany, now 26, was diagnosed at age 10. CF is a genetic disease caused by a failure of cells to properly regulate chloride permeability in the body's cells, leading to a form of mucus buildup in various tissues. Early on, Tiffany's case was more subtle than most, and it therefore took longer to diagnose. Her initial testing while still a baby was inconclusive.
At age 10, Tiffany suffered a bacterial pneumonia with the bacterium Psuedomonas aeruginosum, unusual except in immune suppressed and CF patients. This led doctors to her diagnosis. Later genetic testing confirmed the diagnosis. Uncommon at that time, today all 50 states screen early for CF.
CF is known as an orphan disease, one with little government funding directed towards its management or cure. This is because there are just 30,000 affected individuals in the US and just 70,000 worldwide. Fundraising for research must be raised privately by parents like her in a process known as "venture philanthropy. The book "Breath from Salt" explains much of the history of the disease and its management.
Today pharmaceutical companies have developed four biochemical "modulators" each of which help a percentage of affected patients. The first 3 developed helped very small percentages, but the 4th is able to help up to 90% of patients. In 2020 the patient registry documented fewer lung transplants and more numerous pregnancies among CF patients in part due to this 4th modulator. Survival among patients has now increased from 29 to 50 years old.
There is no cure at this time and the most difficult and costly work to find a cure remains ahead. The CT Chapter is located in Middletown and fundraising events are held across the state. Many opportunities to be involved exist, including walks, which are important because they allow CF patients to participate while avoiding close contact with others to avoid infection transmission. Ironically the Covid-19 pandemic brought the rest of the world's infection control standards up to those that CF patients have had to live with all their lives.
The lives of CF patients are not simple or easy. Melanie's daughter Tiffany must rise extra early each day to have the time to nebulize and to wear a "shaking vest", needed to free mucus from her lungs. She also has antimicrobial resistant bacteria in her lungs all the time and that can lead to an abrupt need for hospitalization to address.
Gary Roman asked for more detail about the CF modulators. A: There are two main types of modulators: "potentiators" and "correctors." The abnormal CF gene codes for an abnormal CF protein, whereas the normal one is shaped like a tunnel that can be closed by a gate to control chloride flow. Potentiators hold the gate open in the abnormal protein, allowing chloride to flow through the cell membrane properly. The drug Kalydeco® (ivacaftor) is a potentiator.
The second type of CF modulator is called a “corrector.” Correctors help the CF protein to form the right 3-D shape so that the protein can facilitate chloride movement more easily.
Nearly 90 percent of people with CF have at least one copy of the gene mutation which prevents the CF protein from forming the right shape. Corrector drugs help it form that right shape.
Correctors used in combination with potentiators work synergistically to lessen the symptoms of CF. In the newest modulator on the market, the correctors elexacaftor and tezacaftor are combined with potentiator ivacaftor to form Trikafta®, a triple combination used to treat people with CF who have a particular CF gene mutation.
Ivacaftor and lumacaftor, components of Orkambi®, are sometimes called “first-generation modulators” because they were the first modulators approved to treat people with CF. Tezacaftor, approved in February 2018 as part of Symdeko®, is also considered a first-generation modulator.
Elexacaftor is considered to be part of the “next-generation” modulators, which are potentially more effective than the first-generation modulators. Other next-generation therapies are in development. They also are likely to be part of a triple-combination therapy to provide more people with CF a variety of treatment options. It is important to have alternatives because individuals respond differently to these drugs. In addition, not everyone can safely take currently approved modulators as some experience side effects, have drug interactions, or have mutations that are not responsive.
Each of the three drugs in a triple-combination therapy addresses a different aspect of the defective CF protein at the same time. In combination, the results are often better than using one or two of the drugs alone.
Rollie Sterrett asked if there have been further effects on Melanie's family. What about the next generations? A: Both parents need the gene defect for the disease to occur. Tiffany received two defective genes, but Melanie's son is fortunate to only have one. If her son has children, his children will have a 1 in 4 chance of getting the disease if his eventual wife is also a carrier. OB/Gyns do screenings for CF genes today if a family history exists. Some individuals without a history might not suspect they carry the gene and may not ask to be screened.
Doug Morehouse asked about CRISPR technology use and Melanie affirmed it was used in CF research, for example the "non-embryonic CRSPR research on CF" project. CRISPR is a technology used to edit genes. Learn more about CRISPR, here: https://www.webmd.com/cancer/guide/crispr-facts-overview
Salin Low noted that in her ministry training she had called on a CF patient who endured "coupage" before the shaking vests were created. [Ed. Note: The word coupage, in the medical context means to "hit" or strike, and is considered a form of "percussion" therapy. When performed correctly, it can be beneficial in loosening and removing excess secretions from the lungs. Many respiratory conditions result in an accumulation of secretions within the lungs that, due to great viscosity and other patient factors, cannot be easily cleared.]
An emotional Lou Daniels asked that we say a prayer together, and then led a prayer for Tiffany, her mother Melanie and other children affected by CF. Thank you Lou!
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