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Stem cell-gene therapy shows promise in ALS safety trial

Cedars-Sinai investigators have developed an investigational therapy using support cells and a protective protein that can be delivered past the blood-brain barrier. This combined stem cell and gene therapy can potentially protect diseased motor neurons in the spinal cord of patients with amyotrophic lateral sclerosis, a fatal neurological disorder known as ALS or Lou Gehrig’s disease.

In the first trial of its kind, the Cedars-Sinai team showed that delivery of this combined treatment is safe in humans. The findings were reported today in the peer-reviewed journal Nature Medicine.

“Using stem cells is a powerful way to deliver important proteins to the brain or spinal cord that can’t otherwise get through the ,” said senior and corresponding author Clive Svendsen, Ph.D., professor of Biomedical Sciences and Medicine and executive director of the Cedars-Sinai Board of Governors Regenerative Medicine Institute. “We were able to show that the engineered stem cell product can be safely transplanted in the human spinal cord. And after a one-time treatment, these cells can survive and produce an important protein for over three years that is known to protect that die in ALS.”

Quantifying Biological Age: Blood Test #5 in 2022

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Papers referenced in the video:

Digit specific denervation does not inhibit mouse digit tip regeneration

It is long-established that innervation-dependent production of neurotrophic factors is required for blastema formation and epimorphic regeneration of appendages in fish and amphibians. The regenerating mouse digit tip and the human fingertip are mammalian models for epimorphic regeneration, and limb denervation in mice inhibits this response. A complicating issue of limb denervation studies in terrestrial vertebrates is that the experimental models also cause severe paralysis therefore impairing appendage use and diminishing mechanical loading of the denervated tissues. Thus, it is unclear whether the limb denervation impairs regeneration via loss of neurotrophic signaling or loss of mechanical load, or both. Herein, we developed a novel surgical procedure in which individual digits were specifically denervated without impairing ambulation and mechanical loading. We demonstrate that digit specific denervation does not inhibit but attenuates digit tip regeneration, in part due to a delay in wound healing. However, treating denervated digits with a wound dressing that enhances closure results in a partial rescue of the regeneration response. Contrary to the current understanding of mammalian epimorphic regeneration, these studies demonstrate that mouse digit tip regeneration is not peripheral nerve dependent, an observation that should inform continued mammalian regenerative medicine approaches.

The first spatiotemporal map of brain regeneration in the axolotl

A multi-institute research team led by BGI-Research has used BGI Stereo-seq technology to construct the world first spatiotemporal cellular atlas of the axolotl (Ambystoma mexicanum) brain development and regeneration, revealing how a brain injury can heal itself. The study was published as a cover story in the latest issue of Science.

The research team analyzed the development and regeneration of salamander brain, identified the key neural stem cell subsets in the process of salamander brain regeneration, and described the reconstruction of damaged neurons by such stem cell subsets. At the same time, the team also found that brain regeneration and development have certain similarities, providing assistance for cognitive brain structure and development, while offering new directions for research and treatment of the nervous system.

In contrast to mammals, some vertebrates have the ability to regenerate multiple organs, including parts of the central nervous system. Among them, the axolotl can not only regenerate organs such as limbs, tail, eyes, skin and liver, but also the brain. The axolotl is evolutionarily advanced compared to other teleost, such as zebrafish, and its brain features a higher similarity to mammalian brain structure. Therefore, this study used the axolotl as an ideal model organism for research into brain regeneration.

Remarkable Anti-Aging Drug Delivers Positive Effects on Health and Lifespan With Brief Exposure

Imagine being able to take a medicine that prevents the decline that comes with age and keeps you healthy. Scientists are searching for drugs that have these effects. The current most promising anti-aging drug is Rapamycin. It is known for its positive effects on life and health span in experimental studies with laboratory animals. It is often given lifelong to obtain the maximum beneficial effects of the drug. However, even at the low doses used in the prevention of age-related decline, negative side effects may occur. Plus, it is always desirable to use the lowest effective dose. A research group at the Max Planck Institute for Biology of Aging in Cologne, Germany, has now shown in laboratory animals that brief exposure to rapamycin has the same positive effects as lifelong treatment. This opens new doors for a potential application in humans.

Research scientists are increasingly focused on combating the negative effects of aging. Lifestyle changes can improve the health of older people, but these alone are not sufficient to prevent the ills of older age. Repurposing existing medications for ‘geroprotection’ is providing an additional weapon in the prevention of age-related decline.

Currently, the most promising anti-aging drug is rapamycin, a cell growth inhibitor and immunosuppressant that is normally used in cancer therapy and after organ transplantations. “At the doses used clinically, rapamycin can have undesirable side effects, but for the use of the drug in the prevention of age-related decline, these need to be absent or minimal. Therefore, we wanted to find out when and how long we need to give rapamycin in order to achieve the same effects as lifelong treatment,” explains Dr. Paula Juricic. She is the leading investigator of the study in the department of Prof. Linda Partridge, director at the Max Planck Institute for Biology of Aging.

Plasma Dilution Appears to Rejuvenate Humans

The trial was only on 8 people, but it appears to have worked well across the board.


Published in GeroScience, a groundbreaking study from the renowned Conboy lab has confirmed that plasma dilution leads to systemic rejuvenation against multiple proteomic aspects of aging in human beings.

This paper takes the view that much of aging is driven by systemic molecular excess. Signaling molecules, antibodies, and toxins, which gradually accumulate out of control, cause cells to exhibit the gene expression that characterizes older cells.

While the bloodstreams of old and young mice have been joined in previous experiments with substantial effects [1], this heterochronic parabiosis approach is neither feasible nor necessary for human beings. Instead, this paper focuses on therapeutic plasma exchange (TPE), a procedure that simply replaces blood plasma with saline solution and albumin. This procedure has already been used to dilute pathogenic, toxic compounds [2], the systemic problems associated with autoimmune and neurological disorders, including Alzheimer’s [3], and even the lingering aftereffects of viral infection [4].

Existential Hope Special with Morgan Levine

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In the Existential Hope-podcast (https://www.existentialhope.com), we invite scientists to speak about long-termism. Each month, we drop a podcast episode where we interview a visionary scientist to discuss the science and technology that can accelerate humanity towards desirable outcomes.

Xhope Special with Foresight Fellow Morgan Levine.

Morgan Levine is a ladder-rank Assistant Professor in the Department of Pathology at the Yale School of Medicine and a member of both the Yale Combined Program in Computational Biology and Bioinformatics, and the Yale Center for Research on Aging. Her work relies on an interdisciplinary approach, integrating theories and methods from statistical genetics, computational biology, and mathematical demography to develop biomarkers of aging for humans and animal models using high-dimensional omics data. As PI or co-Investigator on multiple NIH-, Foundation-, and University-funded projects, she has extensive experience using systems-level and machine learning approaches to track epigenetic, transcriptomic, and proteomic changes with aging and incorporate.
this information to develop measures of risk stratification for major chronic diseases, such as cancer and Alzheimer’s disease. Her work also involves development of systems-level outcome measures of aging, aimed at facilitating evaluation for geroprotective interventions.

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