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What Is Autosomal Recessive Cystic Fibrosis, And Who Does It Affect?

Cystic fibrosis (CF) is an autosomal recessive condition. This means that a person will have CF only if they receive the affected gene from both parents at conception.

Cystic fibrosis (CF) is a condition in which thick mucus causes damage to the lungs, the digestive system, and other organs throughout the body. CF is genetically inherited, which means it's passed down through genes when sperm meets an egg.

Learn more about cystic fibrosis.

CF is a disease that is inherited in an autosomal recessive manner. The word "autosomal" means that the affected gene is located on a numbered chromosome. "Recessive" means that a person must inherit affected genes from both biological parents to develop the disease.

So, autosomal recessive cystic fibrosis can be more simply referred to as cystic fibrosis. In CF, the secretions that are meant to protect and lubricate the organs — such as mucus, sweat, and saliva — become thick. They may cause blockages in different areas of the body, inflammation, and even infections.

Again, a person must inherit one affected gene from each parent to develop CF. Someone who inherits just one affected gene is considered a carrier of CF and can pass the gene to any children they conceive.

CF is caused by mutations to the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Changes to the CFTR gene affect the proteins that regulate chloride and sodium (salt) exchange between cells.

When this gene is affected, the normally thin and slippery secretions in the body become thick. Thickened secretions may block tubes, ducts, and other passageways to the organs throughout the body.

CF primarily affects the lungs and airways, the gastrointestinal tract, and the pancreas. It may also affect the sweat glands and the genitourinary system, which includes the genitals and urinary tract.

Signs and symptoms of CF may appear soon after a baby is born. The thick mucus can build up in a baby's lungs. It can also make sweat and digestive fluids thicker, causing issues in other parts of their body.

Respiratory signs and symptoms may include:

Other possible signs and symptoms include:

A doctor may diagnose CF by observing the signs and symptoms during a physical examination and taking a family history. In the United States, newborn screening for CF is typically performed with a simple heel prick within the first 3 days after birth.

To confirm the diagnosis, a doctor may suggest a sweat chloride test. During this procedure, doctors use a chemical combined with a weak electrical current to make the skin sweat. They then measure and analyze the sweat to look at its salt content. Saltier sweat may indicate that a person has CF.

Genetic (DNA) testing is another way to confirm a CF diagnosis. Doctors can use a blood test to look for CFTR mutations.

Treatment for CF can improve symptoms and quality of life, but it will not cure the disease. A person with CF may see several health professionals in different specialties (such as pulmonologists, dietitians, and respiratory therapists) to address symptoms of CF and the resulting complications.

Treatment includes:

Two drugs specifically used to treat CF are Pulmozyme (to thin and clear mucus) and Kalydeco (to help with the movement of chloride in the cells). Other drugs used for CF include Orkambi, Symdeko, and Trikafta.

Severe CF may cause significant damage to the lungs. In these cases, a lung transplant may help but is carried out on a case-by-case basis.

The main risk factor for developing CF is having a history of the disease on both sides of your biological family.

CF is more common among white people but can affect anyone.

Until recent years, a child with CF typically did not live beyond childhood. But as a result of early screening and improved treatments, a child who receives a CF diagnosis today may live into their thirties or forties or even longer.

What is an autosomal recessive disorder?

An autosomal recessive disorder is a condition that a person will develop only if they inherit affected genes from both parents during conception.

Does a lung transplant cure CF?

No. CF affects the way the cells transport chloride, causing thickened secretions that can damage the lungs. A lung transplant can address lung symptoms but cannot address the way the cells operate throughout the body.

What percentage of people carry the CF gene mutation?

According to the American Lung Association, about 30,000 people in the United States live with CF. Beyond that, around 1 in 30 people (3.3%) in the United States carry the gene for CF.

CF is an autosomal recessive condition inherited during conception. Doctors have made strides in the treatment of CF, and earlier detection and more advanced treatments have helped improve quality of life and extend life expectancy.

If you have a family history of CF and want to have biological children, talk with your doctor. You may want to consider genetic testing and genetic counseling to find out the chances that your child will have CF.

Intellia, ReCode Partner On Genetic Medicines For Cystic Fibrosis

Intellia Therapeutics will work with a private biotechnology company to develop genetic medicines for cystic fibrosis, with an initial focus on people who have limited or no available treatment options.

The collaboration pairs Intellia's gene editing platform, which is based on Nobel Prize-winning CRISPR technology, with ReCode Therapeutics' method for delivering genetic medicines to specific organs.

With cystic fibrosis, mutations in a gene named CFTR causes thick mucus to accumulate in the lungs and other organs. This can lead to serious health issues, including respiratory failure and life-threatening infections.

"By combining our highly synergistic technologies and capabilities, we are excited about the potential to enable a faster path for next-generation gene editing therapeutics to CF patients," said Shehnaaz Suliman, ReCode's CEO, in a Thursday statement announcing the deal.

In that statement, Intellia noted how its platform includes "DNA writing" technology, a tool that has attracted considerable interest and investment in recent years. Tessera Therapeutics, for example, was created by Flagship Pioneering — the same biotech incubator that founded Moderna — and is built around "gene writing" technology that it claims can alter DNA in various ways, from changing single units of genetic material to adding in entire genes.

Those qualities may make gene writing especially useful in diseases like cystic fibrosis where the genetic causes are well understood. Last year, the Cystic Fibrosis Foundation, a patient advocacy group, partnered with Flagship to create potentially curative treatments using technology from some the latter's portfolio companies. The deal, like that of Intellia and ReCode, is prioritizing patients for whom there aren't drugs available.

In the U.S., medicines developed by Vertex Pharmaceuticals are, by the company's estimates, able to treat about 90% of cystic fibrosis patients. The remaining 10% have different mutations that make them ineligible for Vertex's therapies. Experts believe genetic therapies offer the best shot at treating these patients.

Intellia, per its new agreement, will be responsible for the "editing strategy" and components of the experimental therapies. ReCode, meanwhile, will lead the subsequent development of these therapies through preclinical and human testing. ReCode will also lead global commercialization efforts for certain programs that emerge from the collaboration.

Financial terms of the deal weren't disclosed. But the companies did say Intellia will be eligible to receive development and commercial milestone payments, as well as sales royalties from products stemming from the collaboration. Additionally, it can exercise an option to lead commercialization in the U.S. For certain programs.

Genetic Testing: The Good, The Bad, And The Costly

Genetic testing offers certain benefits, limitations, and economic impact.

Midjourney

When the Human Genome Project concluded 21 years ago, it opened the door for genetic testing and a promise for lifesaving screenings and personalized medicine. An innovation that serves as a key foundation for revolutionizing healthcare also presents significant complexities and challenges.

For those in senior leadership managing payment integrity for health plans, understanding genetic testing's multifaceted nature – its benefits, limitations, and economic impact – is essential.

The Promise of Genetic Testing

At its core, genetic testing involves analyzing genes to identify mutations or variants that could indicate a predisposition to, or the presence of, certain diseases. The applications are vast and profoundly impactful. For instance, identifying mutations in the BRCA gene can signal an increased risk of breast cancer, while a diagnosis of Lynch syndrome can lead to proactive measures against colon cancer.

Current technology, known as Next-generation sequencing, has also decreased the cost of genetic testing. In 2007, the estimated cost to sequence a human genome was a million dollars. Today, that cost has been advertised as low as $600.

These tests, which can be conducted through blood, saliva, or tissue samples, offer hope in diagnosing conditions like Down syndrome, cystic fibrosis, Tay-Sachs disease, and many others. By understanding a patient's genetic makeup, healthcare providers can tailor treatment plans, potentially averting severe health outcomes.

No single genetic test can identify all genetic conditions. There are many genetic test types, including single gene testing, panel tests, whole exome/genome sequencing, chromosomal tests, gene expression, and biochemical tests. Biotech and pharma companies continue researching and investing in genetic testing and gene therapies.

It should be noted that clinical genetic tests, distinct from direct-to-consumer (DTC) tests, are specifically ordered by healthcare professionals for medical purposes. In contrast, DTC tests are often chosen by healthy individuals curious about various traits, including ancestry, medication responses, or potential risks for complex conditions.

The Challenges and Limitations

Genetic testing pathways are rife with uncertainties. Predictive tests often yield probabilistic results, not definitive answers, leaving patients uncertain, especially when no effective treatments or therapies exist for their conditions.

According to the CDC: "Despite the many scientific advances in genetics, researchers have only identified a small fraction of the genetic component of most diseases. Therefore, genetic tests for many diseases are developed on the basis of limited scientific information and may not yet provide valid or useful results to individuals who are tested."

Additionally, the intricate interplay between genetics and environmental factors in diseases like coronary heart disease or Alzheimer's remains poorly understood—genetic tests can fall short in predicting these complex interactions.

The Economic Perspective

From an economic standpoint, genetic testing represents both a significant investment and a source of financial complexities. In the last decade, the number of genetic test products has skyrocketed by 1650%, leading to a staggering present-day count of over 175,000 available tests—with 10 new tests entering the market every day.

Despite constituting only 10% of all tests, genetic tests account for 30% of lab-related spending, reflecting their high cost and increasing utilization. And until recently, there was no ID system to differentiate all 175k tests individually.

Fraud represents another significant challenge, exemplified by a recent $463 million fraud involving genetic testing. This case, just one of many involving call centers, fake prescriptions, and deceptive insurance billing, highlights the susceptibility of this sector to exploitation due to its complexity and rapid growth.

Genetic tests represent a disproportionate source of payment errors, appeals, and overturns. This is partly because the relationship between tests, codes, and criteria is unclear or rapidly changing. There are around 800 CPT codes to represent genetic tests for reimbursement.

Common oncology, prenatal, and pharmacogenetic tests are billed with as many as 8-10 codes. Taking into account disease classification codes, genetic tests are billed in more than 2.2 million code combinations—, leading to confusion and inefficiency. Unlike drugs, genetic tests are not required to undergo clinical studies before entering the market.

Implications for Health Plans

Streamlining the review process for genetic testing is imperative, given the high costs and administrative burden associated with evaluating medical necessity. Insurance carriers responsible for safeguarding against medical waste and abuse often face challenges in determining the necessity of such tests. This typically involves scrutinizing medical records, a task that delays claim payments and adds to the patients' and providers' burdens through potential balance billing and increased paperwork.

The process demands significant expertise, especially when specialized analysis is required. If carriers lack in-house specialists, independent medical examiner (IME) reviews become necessary, further escalating overhead costs. These include handling by claim policy specialists, preparation by clinical staff, and detailed analysis by medical directors, not to mention the additional layers of second-level appeals and independent review organization (IRO) evaluations. Consequently, the operational efficiency of health plans is often stretched to its limits by the complexities of reviewing genetic testing.

Though they make up only 1% of all health plan claims, genetic tests often account for 15-20% of the medical services reviewed manually by health plans (e.G. Prior authorizations and claim reviews). This is a critical inefficiency that must be resolved to deliver precision medicine to health consumers efficiently. In addition, one-third of genetic tests are reportedly ordered in error, often due to clinicians' lack of training in this specialized field. This leads to unnecessary spending and can adversely impact patient care and outcomes.

Navigating the Future

As we move forward, it's essential for health plans to adapt to this evolving landscape. Embracing advanced technologies like AI and machine learning can help manage the complexities of genetic test billing and reduce the incidence of fraud, waste, and abuse.

Solutions include:

The use of a comprehensive registry, whose database provides an authoritative, up-to-date view of the testing market, as well as enabling test identification and serving as a single source of truth to link test, coding, and coverage information.

Payment and medical policies adopted by the plan that address inconsistencies in genetic testing billing—including unbundling and stacking codes through edits, provide clarity in medical policy coverage and consistency in plan decisions, plus complement and streamline a health plan's prior authorization process.

Appropriate integration of claim edits that minimize pre-payment reviews, appeals, and provider abrasion.

It is also crucial that provider organizations, independently or through stronger alignment with payers, incorporate comprehensive training programs for clinicians on the appropriate use of genetic tests can significantly reduce errors in ordering these tests, leading to more effective patient care and optimized resource utilization.

Conclusion

Genetic testing stands at the crossroads of groundbreaking medical advancements and complex challenges. While it opens doors to personalized medicine and early disease detection, it also brings forth issues of cost, complexity, and ethical considerations.

As leaders in the healthcare sector, stakeholders must navigate this terrain thoughtfully, leveraging technology and education to harness the benefits of genetic testing while mitigating its challenges. The journey is complex, but the potential rewards for patient care and healthcare economics are immense.

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