Super-Speedy Diagnosis of Rare Genetic Diseases

About a year ago, Matthew Kunzman’s heart was failing, despite doctors’ best attempts to bolster it with every pump and gadget they could think of. But the 14-year-old has bounced back in large part due to super-speedy genetic sequencing that pinpointed the cause of his disease and helped doctors decide how to treat it — in just 11 and a half hours. That speedy diagnosis — faster than any other medical team has previously reported — resulted from a new approach to DNA sequencing to help patients with deadly and rare diseases. On Wednesday, a team of Stanford researchers and collaborators published a letter in the New England Journal of Medicine reporting that they had sequenced 12 seriously ill patients and successfully diagnosed five of them (including Matthew). In all five cases, the information led to tangible changes in how patients were treated.

Typical turnaround time for diagnosis was around eight hours and as short as seven hours and eighteen minutes – less than half the current record. And the scientists are convinced they can cut that in half yet again. Such speed could be life-saving for critically ill patients, according to Euan Ashley, a Stanford cardiologist and the study’s senior author.

You can not only make care better, and help patients more, but do it cheaper, save money, save the system money,” Ashley said. “It seems like a win, win, win all around.”

There’s a lot to be learned by exploring your genetic code, which influences everything from your height and eye color to your likelihood of developing certain diseases. For doctors, knowing whether a patient’s symptoms are linked to specific DNA mutations — and, if so, which ones — can help them determine what treatments and surgical procedures to try and which ones to avoid. But it typically takes weeks to run, process, and interpret sequencing results. That’s time some patients don’t have. And hospital stays spent chasing down the cause of an unknown disease can cost tens of thousands of dollars.

Ashley wanted to see how quickly he could speed things up. He and his team enrolled a dozen seriously ill patients admitted at Stanford, taking about half a teaspoon of blood from each of them for genetic sequencing. The participants, who ranged in age from 3 months to 57 years old, suffered from everything from seizures to cardiac arrest. Throughout the six-month study, which kicked off in December 2020, researchers tweaked nearly every step of the sequencing process, from having someone run samples from the hospital to the lab to shortening the time needed to prep DNA for sequencing. It was round-the-clock work.

Source: https://www.statnews.com/

Genetic Test To Detect Earlier Alzheimer’s

A new study published in the journal Epigenetics in February 2020 reports that changes in the methylation status of the Presenilin 1 (PSEN1) gene could help diagnose Alzheimer’s disease (AD) earlier. This study shows for the first time that methylation of this gene is a common feature in AD.

AD is a widespread dementia disorder, involving the loss of cognitive skills such as thinking, making decisions, remembering things in connection, and learning. It affects almost 50 million people the world over, mostly over the age of 60 years but a significant percentage at ages below 50 years. Furthermore, this is only a fourth of all cases, because most patients go undiagnosed.

 

The progressive and incurable nature of this disorder makes it difficult to bear for both the patient and the caregivers. The disease inevitably progresses to the point where complete care is required. Currently, available medications must be given early to have the highest odds of successfully delaying the onset of severe cognitive loss.

The PSEN1 gene is part of a protease complex that catalyzes a process called regulated intramembrane proteolysis. It is important in AD because it is responsible for cleaving the beta-amyloid fragment from the parent AβPP molecule. It is one of several polymorphic genes that regulate normal embryonic regulation but also promote the risk of AD.

Epigenetic modification is an important way to regulate gene activity in the body and can be triggered by environmental factors, including specific lifestyle and nutritional factors. The addition of methyl groups to the DNA (mostly to the cytosine) outside the actual genetic code, called methylation, is a well-known epigenetic modification. Methylation is typically a method to silence or downregulate the associated gene.

Earlier animal studies have shown that the PSEN1 gene can be downregulated, causing a condition very like AD.  However, little research has been done epigenetic modification of the human PSEN1 gene. It is established that people with AD already show altered PSEN1 behavior. The current study is the first to record the frequent occurrence of DNA methylation at this gene in humans with AD.

Source: https://www.news-medical.net/

Nano Packets Of Genetic Code Seed Cells Against Brain Cancer

In a “proof of concept” study, scientists at Johns Hopkins Medicine say they have successfully delivered nano-size packets of genetic code called microRNAs to treat human brain tumors implanted in mice. The contents of the super-small containers were designed to target cancer stem cells, a kind of cellularseed” that produces countless progeny and is a relentless barrier to ridding the brain of malignant cells.

Nanoparticles releasing microRNAs (light blue) inside a human brain cancer cell

Brain cancer is one of the most widely understood cancers in terms of its genetic makeup, but we have yet to develop a good treatment for it,” says John Laterra, MD, PhD, professor of neurology, oncology and neuroscience at the Johns Hopkins University School of Medicine and a research scientist at the Kennedy Krieger Institute. “The resilience of cancer stem cells and the blood-brain barrier are major hurdles.

Blood that enters the brain is filtered through a series of vessels that act as a protective barrier. But this blood-brain barrier blocks molecular medicines that have the potential to revolutionize brain cancer therapy by targeting cancer stem cells, says Laterra.

To modernize brain tumor treatments, we need tools and methods that bypass the blood-brain barrier,” says Jordan Green, PhD, professor of biomedical engineering, ophthalmology, oncology, neurosurgery, materials science and engineering and chemical and biomolecular engineering at the Johns Hopkins University School of Medicine. “We need technology to safely and effectively deliver sensitive genetic medicines directly to tumors without damaging normal tissue.

A case in point, Green says, is glioblastoma, the form of brain cancer that Arizona Sen. John McCain is battling, which often requires repeated surgeries. Doctors remove the brain tumor tissue that they can see, but the malignancy often returns quickly, says Laterra. Most patients with glioblastoma live less than two years after diagnosis.

Results of the experiments were published online in Nano Letters.

Source: https://engineering.jhu.edu/