Lifeboat Foundation

The viral ALS Ice Bucket Challenge a few years ago raised major funding that resulted in the discovery of new genes connected to the disease. One of those genes is NEK1, in which mutations have been linked to as much as 2% of all ALS cases, making it one of the top-known causes of the disease.

But it wasn’t known how the mutated gene disrupts the function of the motor neuron and causes it to degenerate and die.

Northwestern Medicine scientists have discovered for the first time how this mutated gene leads to ALS (amyotrophic lateral sclerosis).

A recent study found increased cardiac arrhythmia risk to stay long term in individuals with epilepsy, specially in people who use carbamazepine and valproic acid. The findings of the study were published in European Heart Journal.

Using UK Biobank data, the research also explores the potential roles of genetics and antiseizure medications (ASMs) in this complex relationship. Encompassing 329,432 participants, the study included 2,699 with epilepsy, was initiated between 2006 and 2010. Using advanced statistical techniques like Cox proportional hazards models and competing risk models, the researchers aimed to determine the association between epilepsy history and the incidence of cardiac arrhythmias over an extended period.

Individuals with epilepsy displayed a staggering 36% increased risk of experiencing any form of cardiac arrhythmia compared to those without the condition. This risk extended to specific arrhythmia subtypes, including atrial fibrillation, where a 26% increased risk was identified. More alarmingly, the risk of other cardiac arrhythmias was found to be 56% higher in epilepsy patients.

Human cells evolving in the laboratory undergo a series of predictable, sequential genetic changes that lead to pre-cancer. Blocking these changes may allow intervention before cancer occurs.

For prospective parents who are carriers of many inherited diseases, using in vitro fertilization along with genetic testing would significantly lower health care expenditures, according to researchers at Stanford Medicine.

Preimplantation genetic diagnostic testing during IVF, or PGD-IVF, is being used to screen for single-gene defect conditions such as cystic fibrosis, sickle cell disease and Tay-Sachs disease, along with nearly 400 others.

Continue reading “Screening during IVF for inherited diseases greatly reduces costs of care” »

This story is part of a series on the current progression in Regenerative Medicine. In 1999, I defined regenerative medicine as the collection of interventions that restore to normal function tissues and organs that have been damaged by disease, injured by trauma, or worn by time. I include a full spectrum of chemical, gene, and protein-based medicines, cell-based therapies, and biomechanical interventions that achieve that goal.

As part of a trio of stories on advances in stem cell gene therapy, this piece discusses how to alter blood stem cells using mRNA technology. Previous installments describe how the same platform could reinvent how we prepare patients for bone marrow transplants and correct pathogenic DNA.

At present, the only way to cure genetic blood disorders such as sickle cell anemia and thalassemia is to reset the immune system with a stem cell transplantation. Only a fraction of patients elects this procedure, as the process is fraught with significant risks, including toxicity and transplant rejection. A preclinical study published in Science explores a solution that may be less toxic yet equally effective: mRNA technology. The cell culture and mouse model experiments offer a compelling avenue for future research to enhance or replace current stem cell transplantations altogether.

A team of geneticists and systems biologists at Stanford University has associated 169 genes that with the production of melanin in the skin, hair and eyes. In their study, reported in the journal Science, the group conducted a flow cytometry analysis and genome-wide CRISPR screen of cell samples.

Prior research has shown that the production and distribution of melanin in the body is responsible for skin tone, hair color and eye pigmentation. Such characteristics are important for more than appearance’s sake; skin with more melanin, for example, is better able to protect against ultraviolet radiation. In this new effort, the researchers noted that while many of the genes responsible for melanin production have been identified, many more have not.

The researchers began with an effort to differentiate high and low melanin melanocytes—the cells that make melanin. They used the light-reflecting properties of melanin to sort cells in a lab dish by aiming a fluorescent lamp at them. Once they had the cells sorted, they edited them using CRISPR-Cas9. Genes were systematically mutated to switch them off and then tested to see how well the cell continued to produce melanin.

PNP editing is emerging as a versatile and programmable tool for site-specific DNA manipulations. An innovative genome-editing technique could enhance the delivery, specificity and targeting of gene-modifying tools for treatments.

The KAUST-developed method combines two molecular technologies: a synthetic family of DNA-like molecules known as peptide nucleic acids (PNAs), and a class of DNA-cutting enzymes known as prokaryotic Argonautes (pAgos).

The PNAs first unzip and slip inside the DNA helix. The pAgos, guided by short fragments of genetic material, then bind the loosened helix at specific target sequences and nick each opposing strand of DNA.

Summary: Researchers successfully sequenced the entire Y chromosome, previously considered the most elusive part of the human genome.

This feat enhances DNA sequencing accuracy for this chromosome, aiding the identification of genetic disorders. Using state-of-the-art technologies, the team pieced together over 62 million letters of genetic code.

This breakthrough, in tandem with the previous reference genome T2T-CHM13, offers the first complete genome for those with a Y chromosome.

Dr. Joni L. Rutter, Ph.D., (https://ncats.nih.gov/director/bio) is the Director of the National Center for Advancing Translational Sciences (NCATS — https://ncats.nih.gov/) at the U.S. National Institutes of Health (NIH) where she oversees the planning and execution of the Center’s complex, multifaceted programs that aim to overcome scientific and operational barriers impeding the development and delivery of new treatments and other health solutions. Under her direction, NCATS supports innovative tools and strategies to make each step in the translational process more effective and efficient, thus speeding research across a range of diseases, with a particular focus on rare diseases.

By advancing the science of translation, NCATS helps turn promising research discoveries into real-world applications that improve people’s health. The NCATS Strategic Plan can be found at — https://ncats.nih.gov/strategicplan.

Continue reading “Dr. Joni L. Rutter, Ph.D. — Director, National Center for Advancing Translational Sciences — NIH” »