Lifeboat Foundation: Safeguarding Humanity
Toggle light / dark theme

Blog

Category: genetics

Inhibiting protein to treat myeloproliferative neoplasms shows preclinical promise

Inhibiting menin, a protein that supports leukemia growth and is already targeted to treat some forms of leukemia, also holds promise for treating myeloproliferative neoplasms. A new study from scientists at St. Jude Children’s Research Hospital showed that inhibiting menin significantly extended survival and reversed multiple disease features in preclinical models. The findings were published today in Cancer Cell.

Menin is best known as a therapeutic vulnerability in certain types of acute leukemia, including those with KMT2A gene rearrangements or NPM1 mutations. Menin inhibitors, such as revumenib, have greatly improved treatment for these cancers and are approved by the Food and Drug Administration (FDA). However, menin inhibition can reduce megakaryocytes (normal platelet-forming cells) and decrease platelet counts. Producing too many megakaryocytes is a hallmark of diseases called myeloproliferative neoplasms, which are slow-developing, rare blood cancers.

John Crispino, Ph.D., MBA, St. Jude Division of Experimental Hematology director and Department of Hematology member, tested whether inhibiting menin could be a viable therapeutic strategy for myeloproliferative neoplasms.

Can Mushrooms Reduce LDL? 53-Test Analysis

Join us on Patreon! / michaellustgartenphd.

Discount Links/Affiliates:
Blood testing (where I get the majority of my labs, for those who blood test with Quest): https://www.ultalabtests.com/partners… those who blood test with LabCorp: https://www.anrdoezrs.net/click-10161… At-Home Metabolomics: https://www.iollo.com?ref=michael-lus… Use Code: CONQUERAGING At Checkout Clearly Filtered Water Filter: https://get.aspr.app/SHoPY Epigenetic, Telomere Testing: https://trudiagnostic.com/?irclickid=… Use Code: CONQUERAGING NAD+ Quantification: https://www.jinfiniti.com/intracellul… Use Code: ConquerAging At Checkout Oral Microbiome: https://www.bristlehealth.com/?ref=mi… Enter Code: ConquerAging SiphoxHealth Blood Testing (ApoB, GrimAge): https://siphoxhealth.com/mlustgarten Green Tea: https://www.ochaandco.com/?ref=fqbtflod Use Code: ML10OFF Diet Tracking: https://shareasale.com/r.cfm?b=139013… If you’d like to support the channel, you can do that with the website, Buy Me A Coffee: https://www.buymeacoffee.com/mlhnrca Conquer Aging Or Die Trying Merch! https://my-store-d4e7df.creator-sprin…

Blood Testing Essentials (Biological Age, CVD-Risk, Kidney Health and Function):
PhenoAge (Biological Age): https://www.ultalabtests.com/partners…

Measure the Bortz biological clock biomarkers: https://www.ultalabtests.com/partners…

Calculate your biological age using the Bortz clock: https://www.longevity-tools.com/human…

Dr. David Sinclair: The First Human Trial of an Age-Reversal Therapy #podcast #lifespan #longevity

Harvard geneticist David Sinclair returns to explain how his lab’s age-reversal technology has moved from mice and primates into FDA-cleared human trials — starting with an attempt to reverse vision loss from glaucoma, a condition considered permanent. Sinclair breaks down the science of Yamanaka factors, why using three genes instead of four sidesteps the cancer risk, and his core thesis: make the body young enough and it can cure its own diseases.

He and James also go deep on the practical longevity playbook: NMN, NAD and Sirtuins, metformin and berberine, testosterone and muscle mass, sleep, diet, and how to separate real science from longevity misinformation. Sinclair shares his own protocol at 56, his 86-year-old father’s results, and teases a next-generation \.

This unusual epigenetic modifier promotes certain cancers but suppresses others

The epigenetic modifier MLL4 has an unassuming name—the 4, for instance, indicates it’s just one in a family of such modifiers. But MLL4 is quite special: In a specific type of leukemia, it drives disease progression, while in solid tumors, it acts as a suppressor.

The paradoxical nature of MLL4 made it a compelling enigma for Rockefeller University’s Robert Roeder, a pioneer in the field of genetic transcription. Now his Laboratory of Biochemistry and Molecular Biology at Rockefeller University has used a combination of biochemistry, genetics and structural biology to find surprising new characteristics of MLL4 that expand our understanding of its range of functions, including its relationship to a tumor-suppressing protein. The findings, published in Molecular Cell, could illuminate how the MLL4 complex helps switch genes on—including cancer genes in leukemia.

“This research demonstrates that MLL4 has functions in transcription that were entirely unknown before,” says Roeder. “And because MLL4 is a key regulator of gene activity, it’s important to understand how it works—especially in cancer cells.”

Genetic mapping identifies new hope for bone diseases

In a global breakthrough published in Nature Genetics, researchers have successfully mapped the cells and genes that regulate bone formation and loss at an unprecedented scale and discovered the critical role that blood vessel cells play in bone health.

By combining genomic sequencing with data from half a million individuals, the research team identified hundreds of previously unknown genes that govern bone health and revealed cells surrounding blood vessels as one of the drivers of bone repair—a role that has been underappreciated until now.

Led by Professor Peter Croucher and Dr. Ryan Chai from the Garvan Institute of Medical Research, Associate Professor John Kemp from Mater Research, and Professor Graham Williams and Professor Duncan Bassett from Imperial College London, the team’s findings fundamentally enhance our understanding of skeletal disease.

Epigenetic mapping provides deeper insight into leukemia

Researchers at Karolinska Institutet in Sweden and Kyoto University in Japan have identified new subgroups of the blood cancer acute myeloid leukemia. The study, published in the journal Nature, shows that changes in the regulation of genes within cells can help explain variation in the disease and influence prognosis and treatment choices.

Acute myeloid leukemia (AML) is an aggressive form of blood cancer in which immature blood cells grow uncontrollably. Despite extensive knowledge of the genetic alterations underlying the disease, it is still difficult to fully understand why patients develop different disease courses. In this study, the researchers analyzed so-called epigenetics—how genes are regulated without changes to the DNA sequence.

New CRISPR method makes it possible to control protein production in cells

The speed at which a cell produces proteins is a decisive factor in determining whether it divides, specializes or retains its stem cell properties. A team of researchers led by Professor Stefan H. Stricker, professor of epigenetic engineering at LMU’s Biomedical Center and research group leader at Helmholtz Munich, has worked with international partners to demonstrate directly for the first time that the amount of ribosomal RNA (rRNA) directly regulates these processes. Their results were published in the journal Science.

It has been established for some time that the amount of ribosomal RNA differs among different types of cells and is altered in a number of diseases. But it remained unclear whether these specific characteristics are the cause or merely the result of biological processes.

With the newly developed CRISPR-based method TAPIR (Targeted Activation of Protein Translation), researchers now have access to a tool that can boost the activity of ribosomal genes and, as a result, influence a cell’s protein production. “Our new study shows that targeted activation of rRNA production significantly increases protein synthesis,” explains Stricker, lead author of the publication.

How a Revolutionary Cancer Treatment Could Reset the Immune Systems of Patients With Autoimmune Diseases

But there are other possible CAR T risks for autoimmune patients. In February, FDA officials published a paper endorsing CAR T’s potential in autoimmunity but warning of “unpredictable long-term toxicity.” CAR T treatment for cancer, the authors noted, has been linked to diverse long-term issues such as Parkinson’s disease. There have also been cases in which the bioengineered cells themselves turned malignant, causing new, T cell-based cancers.

Causing a secondary cancer may be an acceptable risk when treating a life-threatening cancer, but probably not for autoimmunity, says Matt Lunning, medical director for gene and cellular therapy at Nebraska Medicine, in Omaha. How to balance the risk between the impacts of an autoimmune disease, which can range widely in severity, and the difficult-to-quantify risk of future side effects or cancers remains a major open question.

Researchers are already working on second-and third-generation versions of CAR T that they expect to be safer for both cancer and autoimmunity. For example, James Howard, a neuromuscular neurologist at the University of North Carolina at Chapel Hill, is testing a technology from a company called Cartesian Therapeutics that encodes the CAR using molecules of mRNA, the short-lived genetic messenger used in Covid-19 vaccines, instead of long-lasting DNA. The CAR T cells should wipe out B cells for only as long as the mRNA persists, then lose their B cell-targeting abilities. With no chance for genetically modified T cells to hang around long-term, there should be no cancer risk.

PET scans reveal stage-linked tau signal in Huntington’s disease brains

A study conducted by the Sant Pau Research Institute (IR Sant Pau) and Hospital de Sant Pau has identified for the first time in living individuals a brain pattern related to the tau protein that changes according to the stage of Huntington’s disease. This discovery opens the door both to the use of new biomarkers for monitoring the disease and to the development of treatments for a condition for which no therapeutic options are currently available.

Using positron emission tomography—a molecular neuroimaging technique known as PET—and the second-generation radiotracer [¹⁸F]PI-2620, the researchers demonstrated that this signal can already be detected in some mutation carriers who have not yet developed clinically manifest disease and that, as the disease progresses, the signal increases and spreads according to an organized anatomical distribution.

The study, published in the European Journal of Nuclear Medicine and Molecular Imaging, provides new insights into the biological processes that occur between the genetic alteration responsible for the disease and the onset of its motor, cognitive and neuropsychiatric manifestations.

Schizophrenia And Bipolar Disorder Share 70% of Their Genetic Roots, Landmark Study Finds

Researchers are beginning to realize that even vastly different psychiatric disorders can share startlingly similar genetic roots.

In February last year, scientists revealed their discovery that eight different psychiatric conditions all shared a common genetic basis.

Another team then published a follow-up study in Nature in December – the largest of its kind to date.

/* */