How Genetic Testing Will Create Personalized Therapeutics for Rare Diseases

"Personalized medicine represents a better paradigm in medicine than one-size-fits-all, trial-and-error, which is what most medicine is."
September 28, 2021, 1:00pm
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For patients with rare symptoms, landing on a course of treatment often comes only after a long, winding road of doctor’s visits, consultations, lab work and experiments. It’s costly, emotionally turbulent, and tiresome.

It’s what many in the world of medicine call the “diagnostic odyssey,” referring to the time it takes from the initial onset of symptoms to final diagnosis. And it’s a path that, for the average patient, takes about 8 years.

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“You go from doctor to doctor for years and years, and you don't figure out what's going on,” Edward Abraham, founder of the Personalized Medicine Coalition (PMC), an education and advocacy group, told Motherboard. “All of that is expensive.” 

It’s a cycle Abraham’s group, which consists of both non- and for-profit organizations from across the healthcare industry, is striving to do away with. Their solution? Improving access to genetic testing to allow for the creation of personalized therapeutics. 

The traditional approach to medicine, Abraham describes, is one-size-fits-all. When a patient presents a rare, difficult-to-diagnose symptom, their healthcare provider may try a slew of treatments with varying effectiveness, all of which have been developed to treat the largest number of patients at once, rather than to suit the needs of a specific individual.

With personalized medicine, hard-to-diagnose symptoms are inspected by going straight to the source — the human genome. With genetic sequencing, a sample of a patient’s DNA is taken through blood, skin, or tissue, for example. Then, their entire genetic code, all 3.2-billion base pairs, are analyzed for signs of mutations that may be causing a symptom or underlying disorder. With this information, a doctor is better equipped to search for a personalized treatment for an individual disorder, or to create one from scratch. 

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“Personalized medicine represents a better paradigm in medicine than one-size-fits-all, trial-and-error, which is what most medicine is,” Abraham said.

He notes that it’s gotten more efficient and affordable over the last two decades, since the advent of the Department of Energy and the National Institutes of Health’s Human Genome Project. A multinational, 15-year effort, the project set out to determine the order of all genomes in human DNA, creating a resource that could be used to guide medical practice and research for years to come. 

The project cost around $3-billion in 1991 (around $6 billion today) in all. Today, Abraham notes, mapping a patient’s genome “can be done for less than a thousand.” 

And it’s proven applicable in a range of clinical settings. It’s well-understood to successfully diagnose and treat cancer, an “extremely heterogenous disease,” researchers at The Hormel Institute at the University of Minnesota wrote in a 2017 comment in the journal Nature. The authors note that while a single drug has yet to be discovered to cure all cancer patients, precision medicine tailored to the patient will prove more effective down the line, because “every single cancer patient exhibits a different genetic profile.”

More recently, researchers at the Mayo Clinic’s Center for Individualized Medicine have applied genomics to treating cardiovascular disease, major depressive disorder, and breast cancer.

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But genetic testing is also becoming increasingly useful in the presence of rare symptoms. in July, researchers at the University of California San Francisco published a study on the use of genetic sequencing to locate mutations that cause Aromatic L-amino acid decarboxylase (AADC) deficiency, a genetic disorder that starves the brain of the dopamine and serotonin required for basic motor and behavioral skills, like holding up one’s head or saying hello

“The success of this general strategy provides confirmation of targeted gene therapy as a tool to effectively treat other genetic disorders of the central nervous system,” the authors wrote in the report.

Despite evidence of its efficacy in difficult diagnostic settings, Abraham says there remains a dearth of support from insurance companies, who are dubious that the approach is anything more than costly and experimental.

The PMC is devoting its own research dollars to disproving this, most recently via a paper on rare childhood disorders on a sample of data from the Nicklaus Children’s Hospital in Miami. His team tracked the cost of sequencing the genome of a sample of children and prescribing treatment accordingly, and though the paper is not yet published, Abraham is confident that the results point to the cost-effectiveness of the personalized approach. Reducing the steps involved in the “diagnostic odyssey” saves money for patients and insurance companies, alike. It also leads to better patient outcomes. 

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“The system does not encourage that, because the insurance companies generally don't want to pay for that kind of genetic tests,” Abraham said. “One of the things we're doing is trying to demonstrate that there is not only clinical utility for the patient, but it also saves the health system and the payer a lot of money.” 

Next on the docket for the PMC is pushing for the coverage of genetic testing by the Centers for Medicare & Medicaid Services, the federal agency that oversees public insurance coverage. The coalition has been pushing for the passage of the CURES 2.0 Bill, which, among other items, creates a pilot program to test approaches to delivering personalized medicine under Medicaid and Medicare. If passed, it would begin turning the wheels required to make individualized treatments an option for low-income Americans, who otherwise could not afford them. 

“It would make CMS recognize that it was a useful tool in the arsenal,” Abraham said. 

“Deep is what patients want,” he added. “Patients don't want to be cookie cutter.”

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