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Two drugs from a class new to HIV medicine called BH3 mimetics were unveiled at July’s 12th International AIDS Society Conference on HIV Science (IAS 2023) in Brisbane. They may contribute to a cure for HIV by killing off long-lived cells that contain HIV genes in their DNA. Notably, venetoclax (Venclexta) and obatoclax only killed off cells containing intact DNA, capable of giving rise to new viruses, and did not delete cells containing defective, harmless DNA.

A number of drugs and treatments from the anti-cancer arsenal have been investigated as HIV cure research such as HDAC inhibitors, PD-1 inhibitors and therapeutic vaccines. (And, of course, the six successful cures so far have used the radical cancer therapy of a stem cell (bone marrow) transplant.)

This is not coincidental: cancer and AIDS are both the end result of mutations in the DNA of some of our cells. In the case of cancer they arise in the host DNA and in HIV infection they are introduced by a virus, but both are the result of ‘rogue genes’ (some other viruses, such as HPV, directly cause cancers).

One proven method for tracking down the genetic origins of diseases is to knock out a single gene in animals and study the consequences this has for the organism. The problem is that for many diseases, the pathology is determined by multiple genes, complicating the task for scientists trying to pinpoint the contribution of any single gene to the condition. To do this, they would have to perform many animal experiments – one for each desired gene modification.

Researchers led by Randall Platt, Professor of Biological Engineering at the Department of Biosystems Science and Engineering at ETH Zurich in Basel, have now developed a method that will greatly simplify and speed up research with laboratory animals: using the CRISPR-Cas gene scissors, they simultaneously make several dozen gene changes in the cells of a single animal, much like a mosaic.

While no more than one gene is altered in each cell, the various cells within an organ are altered in different ways. Individual cells can then be precisely analyzed. This enables researchers to study the ramifications of many different gene changes in a single experiment.

Though drug developers have achieved some progress in treating Alzheimer’s disease with medicines that reduce amyloid-beta protein, other problems of the disease, including inflammation, continue unchecked. In a new study, scientists at The Picower Institute for Learning and Memory at MIT describe a candidate drug that in human cell cultures and Alzheimer’s mouse models reduced inflammation and improved memory.

The target of the new “A11” molecule is a genetic transcription factor called PU.1. Prior research has shown that amid Alzheimer’s disease, PU.1 becomes an overzealous director of inflammatory gene expression in the brain’s microglia immune cells. A11 suppresses this problematic PU.1 activity, the new research shows, by recruiting other proteins that repress the inflammatory genes PU.1 works to express. But because A11 concentrates mostly in the brain and does not reduce PU.1 levels, it does not appear to disrupt PU.1’s other job, which is to ensure the production of a wide variety of blood cells.

“Inflammation is a major component of Alzheimer’s disease pathology that has been especially hard to treat,” says study senior author Li-Huei Tsai, Picower Professor of Neuroscience at MIT and director of The Picower Institute and MIT’s Aging Brain Initiative. “This preclinical study demonstrates that A11 reduces inflammation in human microglia-like cells, as well as in multiple mouse models of Alzheimer’s disease, and significantly improves cognition in the mice. We believe A11 therefore merits further development and testing.”

A 58-year-old patient with terminal heart disease became the second patient in the world to receive a historic transplant of a genetically-modified pig heart on September 20. He is recovering and communicating with his loved ones. This is only the second time in the world that a genetically modified pig heart has been transplanted into a living patient. Both historic surgeries were performed by University of Maryland School of Medicine (UMSOM) faculty at the University of Maryland Medical Center (UMMC).

The first historic surgery, performed in January, 2022, was conducted on David Bennett by University of Maryland Medicine surgeons (comprising UMSOM and UMMC), who are recognized as the… More.

After world’s first successful transplant in 2022, also performed at the University of Maryland Medical Center (UMMC), this groundbreaking transplant team per.

Continue reading “UM Medicine Faculty-Scientists and Clinicians Perform Second Historic Transplant of Pig Heart into Patient with End-Stage Cardiovascular Disease” »

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In a new study in mice, a team of researchers from UCLA, the Swiss Federal Institute of Technology, and Harvard University have uncovered a crucial component for restoring functional activity after spinal cord injury. The neuroscientists have shown that re-growing specific neurons back to their natural target regions led to recovery, while random regrowth was not effective.

In a 2018 study published in Nature, the team identified a treatment approach that triggers axons —the tiny fibers that link nerve cells and enable them to communicate—to regrow after spinal cord injury in rodents. But even as that approach successfully led to the regeneration of axons across severe spinal cord lesions, achieving functional recovery remained a significant challenge.

Continue reading “Scientists regenerate neurons that restore walking in mice after paralysis from spinal cord injury” »

To make a gene-editing tool more precise and easier to control, Rice University engineers split it into two pieces that only come back together when a third small molecule is added.

Researchers in the lab of chemical and biomolecular engineer Xue Sherry Gao created a CRISPR-based gene editor designed to target adenine ⎯ one of the four main DNA building blocks ⎯ that remains inactive when disassembled but kicks into gear once the binding molecule is added.

Compared to the intact original, the split editor is more precise and stays active for a narrower window of time, which is important for avoiding off-target edits. Moreover, the activating small molecule used to bind the two pieces of the tool together is already being used as an anticancer and immunosuppressive drug.

Still seems unsafe to me until its 100% error free, but step in correct direction at least.

Researchers have found that splitting the gene editor used in traditional CRISPR technology creates a more precise tool that can be switched on and off, with significantly less chance of causing unintended genome mutations. They say their novel tool can potentially correct around half of the mutations that cause disease.

CRISPR is one of those scientific terms that has made it into the everyday lexicon. Arguably one of the biggest discoveries of the 21st century, the gene-editing tool has revolutionized research and the treatment of genetic and non-genetic diseases. But the primary risk associated with CRISPR technology is ‘off-target edits,’ namely unexpected, unwanted, or even adverse alterations at locations in the genome other than the targeted site.

Continue reading “New gene-editing tool reduces unintended mutations by more than 70%” »

Many of the genetic mutations that directly cause a condition, such as those responsible for cystic fibrosis and sickle-cell disease, tend to change the amino acid sequence of the protein that they encode. But researchers have observed only a few million of these single-letter ‘missense mutations’. Of the more than 70 million such mutations that can occur in the human genome, only a sliver have been linked conclusively to disease, and most seem to have no ill effect on health.

So when researchers and doctors find a missense mutation that they’ve never seen before, it can be difficult to know what to make of it. To help interpret such ‘variants of unknown significance’, researchers have developed dozens of computational tools that can predict whether a variant is likely to cause disease. AlphaMissense incorporates existing approaches to the problem, which are increasingly being addressed with machine learning.