Achieving Success with Genetically Modified Patients

Genetic disease diagnosis and gene therapy are still in the early days, but the future impact on patient benefits looks very bright.  With enough high-priced lab equipment, with the right clinicians, and with unfettered access to a patient, an accurate diagnosis can sometimes be discovered.  Isolating the right diagnoses can be very challenging, and not all diseases are genetic.

A few gene therapies have delivered spectacular successes.  Eteplirsen plays a key role in treatment for instances of Duchenne Muscular Dystrophy (DMD).  DMD is caused by mutations in the dystrophin gene which normally stabilizes muscle fibers during contraction.  Eteplirsen modulates splicing of a corrected dystrophin gene and that helps repair normal action during muscle contraction.

In another case, a corrected DNA sequence was delivered by a “viral vector” – a non-pathogenic virus that can pass through the cells’ walls and move the new DNA into the right place in the patient’s chromosomes – to treat choroideremia retinal blindness.  The treatment improved the patients level of vision substantially.  Successes raise hopes in other patients and present useful, possibly relevant clues to researchers who are treating other genetic diseases.

A related collection of genetic therapies comes in the form of stem cell treatments.  The most extensive use of stem cell treatment is for blood stem cell transplantation to rebuild the blood system after cancer treatments.  Some bone, skin and corneal injuries and diseases can be treated with implanted tissues that contain stem cells.  These procedures are widely accepted as safe and effective by the medical community.

At one time the availability of appropriate, safe stem cells was an issue and tissues from embryos were used as the main source.  That distressed some on religious grounds.  Now clinicians can convert many of a patient’s own cells into “induced pluripotent” stem cells (iPSCs) that are suited to multiple types and locations of treatment.  iPSCs can be coaxed to deliver the correct DNA-RNA-protein-functionality that the patient’s diseased tissues had stopped delivering.

The topic of genetics has piqued consumers’ curiosity.  Consumers have embraced the opportunity to learn more about their own genes.  Home testing kits such as 23andMe or Navigenics have made it easy and cheap to receive reports on personal exposures to genetic diseases (e.g., sickle cell).  23andMe also reveals some information on your ancestors’ migrations through different areas of the world.

The do-it-yourself (DIY) genetic tests can suggest which combinations of our lifestyle, prior diseases, and single nucleotide polymorphisms (SNPs) might be relevant to our future health.  SNPs are the slight variations within DNA that can account for differences in our appearance and how we develop genetic diseases.  Of course, the DIY reports can be fallible.  They can underestimate or overestimate a SNP’s importance, or they can overlook or report on a SNP you might not have.  If a report causes you alarm, check with your physician.

Gene therapy results from inserting genetic material into cells so it can compensate for abnormal genes or restore the availability of a beneficial protein.  Different approaches have been used to correct the effects of flawed genes.  In some cases, new genetic tools called CAS9 and CRISPR allow researchers to precisely cut out a flawed DNA sequence within a gene and splice in a lab-created, correct DNA sequence.

The corrected DNA sequence for that cell is then massively replicated and nudged into the patient’s other cells with help of a viral vector.  In clinical trials of genetic treatment, there are often side effects (e.g., production of a wrong protein) that interferes with success and slows down progress.

It is too early to speculate on the eventual, per-treatment costs that will be charged for the many forms of genetic treatments that we can hope to see developed.  Many stem cell treatments are performed with prices above $25,000.  Patching flawed DNA sequences is likely to cost much more.  NIH and FDA generally do not welcome genetic treatments that displace conventional surgery and medicine, which means that most research funding comes from private sources.

We wonder if those who aggressively oppose Genetically Modified Organisms in food crops will accept neighbors who have experienced the equivalent for humans – successful genetic treatment.  Most of us will praise the healthy outcomes of these patients.

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