Emerging Technologies in the Fight Against Genetic Disease

At Singularity University, we believe that to stay ahead you must understand emerging genetic trends, technology, and their potential future impact. Understanding these advancements are critical for your organization and for creating positive impact. In this post, I’ll take a closer look at how exponential tech is shaping the fight against genetic disease.

Cystic fibrosis (CF) is an example of a genetic disease. CF is caused by mutations in a single gene on chromosome 7 that encodes the cystic fibrosis transmembrane conductance regulator (CFTR) protein, which is a complex chloride ion channel and regulatory protein located in exocrine glands. The mutations cause disruption of the normal transport of chloride and other ions such as sodium, which leads to thick secretions in the lungs, digestive system, and reproductive tract. The inadequate removal of these secretions can lead to obstruction, inflammation, and increased infections with an end result of chronic multisystem disease affecting several organs.

CF is the most common life-shortening autosomal recessive disease among Caucasian populations, occurring in 1 in 2,000-3,000 live births, and with up to 1 in 25-35 people carrying the defective gene. Additionally, there are an estimated 70,000 people worldwide living with this disease, for which there is currently no cure. The median predicted survival age for CF patients in the United States is just above 39 years old.

In short, CF is a condition that a person is born with and can cause significant life-limiting disease. The good news is that advancements in the fight against CF are being made with the aid of emerging technologies. For the first time in human history, stem cell transplantation has demonstrated the potential to correct the devastating airway disease often presenting in CF.

X-Ray of the lungs

Stem Cell Transplantation

The airway disease manifested in CF is a major cause of morbidity and mortality for those with the condition. A recent study published in the journal Stem Cell Research and Therapy by researchers from the University of Adelaide in Australia demonstrates the ability to replace CF problematic cells with healthy ones. Their research involves the premise of harvesting adult stem cells from the lungs of CF patients, correcting them via gene therapy, and then reimplanting those cells back into the patient.

A key takeaway from their study was the successful testing of a new transplantation method of reporter gene-expressing cells in mice airways. Their new method involved intentionally denuding part of the airway, thereby eliminating existing surface epithelial cells and allowing for a receptive medium for effective transplantation. The successful transplantation of healthy stem cells then have the potential to differentiate into the full range of cell types in the airway epithelium and may provide an ongoing source of disease-free cells for replenishing the airway during natural cell turnover.

The impact could be the eventual prevention of lung disease onset in young CF patients or the ability to halt lung disease progression in older patients with established disease. Study lead Nigel Farrow stated that continuing to perfect this technique “could significantly improve the lives of those living with cystic fibrosis and potentially combat this chronic life-limiting illness.”

Organoids

Another encouraging technology in the fight against CF is the usage of organoids for therapeutic testing. In particular, this technique is being utilized in the battle against the rarer genetic mutations of CF. Specifically, there are no currently approved therapies that target CF caused by nonsense mutations, which comprise a little more than 10% of all CF patients. Organoids are assisting the search for new therapeutic solutions for this population.

Organoids are self-organized three-dimensional tissue cultures that have been derived from stem cells. They can be manipulated to express certain aspects of a target organ or more generally the complex nature of the entire organ itself. To make that a little easier to understand, you might recall the old anti-drug PSA, “This is your brain. This is your brain on drugs.” That’s what organoids allow us to test, but in a lab setting. They are tiny collections of cells meant to replicate and resemble a target organ (the brain, kidneys, lungs, etc.) so that we can help understand and model different diseases and treatments in the lab on that organ. In this case, a CF patient’s intestinal stem cells are harvested and an organoid with CF is created. New therapeutic drugs in development can then be tested on the organoid for efficacy against CF.

Eloxx Pharmaceuticals is currently developing disease-modifying therapeutics for CF patients with rare nonsense mutations. The biopharmaceutical company has been utilizing organoids to help streamline the research and development of such potential solutions. According to their Chief Medical Officer, Dr. Pedro Huertas, “the use of patient organoids… is rapidly being adopted as a potential surrogate marker likely to predict potential clinical benefit in cystic fibrosis patients by industry, payers, and regulators.” With an average drug discovery cost of over $2 billion for each new drug that makes it to market, organoids have the potential to make this process significantly faster and less expensive. The far-reaching impact of these emerging technologies will be significant for patients and industry players alike. See how we can help your company understand the implications of exponential technologies.

-Dr. Kev

Sources include Epithelial disruption: a new paradigm enabling human airway stem cell transplantation in Stem Cell Research and Therapy, Pharmexec.com, ScienceDaily, Eloxxpharma.com, hsci.harvard.edu, and uptodate.com.