Promising results from CIRM-funded projects

Severe Leukocyte Adhesion Deficiency-1 (LAD-1) is a rare condition that causes the immune system to malfunction and reduces its ability to fight off viruses and bacteria. Over time the repeated infections can take a heavy toll on the body and dramatically shorten a person’s life. But now a therapy, developed by Rocket Pharmaceuticals, is showing promise in helping people with this disorder.

The therapy, called RP-L201, targets white blood cells called neutrophils which ordinarily attack and destroy invading particles. In people with LAD-1 their neutrophils are dangerously low. That’s why the new data about this treatment is so encouraging.

In a news release, Jonathan Schwartz, M.D., Chief Medical Officer of Rocket, says early results in the CIRM-funded clinical trial, show great promise:

“Patients with severe LAD-I have neutrophil CD18 expression of less than 2% of normal, with extremely high mortality in early childhood. In this first patient, an increase to 47% CD18 expression sustained over six months demonstrates that RP-L201 has the potential to correct the neutrophil deficiency that is the hallmark of LAD-I. We are also pleased with the continued visible improvement of multiple disease-related skin lesions. The second patient has recently been treated, and we look forward to completing the Phase 1 portion of the registrational trial for this program.”

The results were released at the 23rd Annual Meeting of the American Society of Gene and Cell Therapy.


These microscopic images show gene expression in muscle stem and progenitor cells as they mature from early development to adulthood (left to right). As part of this process, the cells switch from actively expressing one key gene (green) to another (violet); this is accompanied by the growth of muscle fibers (red).
Photo courtesy: Cell Stem Cell/UCLA Broad Stem Cell Research Center

When you are going on a road-trip you need a map to help you find your way. It’s the same with stem cell research. If you are going to develop a new way to treat devastating muscle diseases, you need to have a map to show you how to build new muscle stem cells. And that’s what researchers at the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at UCLA – with help from CIRM funding – have done.

The team took muscle progenitor cells – which show what’s happening in development before a baby is born – and compared them to muscle stem cells – which control muscle development after a baby is born. That enabled them to identify which genes are active at what stage of development.

In a news release, April Pyle, senior author of the paper, says this could open the door to new therapies for a variety of conditions:

“Muscle loss due to aging or disease is often the result of dysfunctional muscle stem cells. This map identifies the precise gene networks present in muscle progenitor and stem cells across development, which is essential to developing methods to generate these cells in a dish to treat muscle disorders.”

The study is published in the journal Cell Stem Cell.

One thought on “Promising results from CIRM-funded projects

  1. Patients with severe LAD-1 express low levels of CD18 in neutrophils which is less than 2% than normal subjects. However, gene therapy with RP-L201 showed a drastically increase of CD18 expression, from less 1% to 47%. The result showed the efficacy and potential therapeutic of gene therapy to correct neutrophil deficiency.

    The potency of gene therapy to treat the deficiency diseases is high. However, the efficacy of gene therapy is very depended on efficiency of vector to deliver the gene to the target cell and duration of gene expression in cell. The transfer of a normal copy of a single defective gene with gene therapy would immediately revert the disease pathogenesis or even prevent the development of disease. Virus is commonly choosed as gene transfer vectors with high efficiency in cellular entry and high of gene expression. The expression of therapeutic gene is regulated by viral promoter. For instance, the many-fold increase of CD18 expression in neutrophil of LAD-1 patients than normal showed the potency of promoter viral to immediately cure the deficiency of disease. Promoter viral is able to trigger overexppression of DNA in targeted cell. The uncontrollable of DNA expression may contribute transforming event occurring in cell and lead to cancer. The long-term gene therapy may consequently bring more disasters to the patients’ health and lives. The consistency of follow up to determine the health and well being of patients is highly recommended.

    Research of focusing on muscle progenitor cells from fetus before birth and muscle stem cells after birth. The development of human pluripotent stem cells (HPSCs) faced difficulty to identify the position of tissue from muscle development map. On the hand, muscle cells making in the lab were not as functional as the fully matured muscle stem cells in human. In addition, HPSC- derived muscle cells produced by all methods resembled muscle progenitor cells at an early development state but did not align Ito adult muscle stem cells. There was other cell types existed to support muscle cells development.

    Stem cells are moveable. Interaction of cells take place within neighboring cells or far distance from them. Cell-cell interaction may switch on the gene expression and signaling network . The correct sequence of gene expression from one to another is important to regulate the formation of morphology and functioning cells. In some occasion, two or more genes interplay together to regulate the development of mature cells. Data from morphology and biological changers of cells together with gene expression network provide greater advantage for laboratory to develop tissues for future meditation. However, human are higher degree of organisms. The program of tissues and organs development is highly complicated. Although human and mouse have very high homologous of genome sequence. The different structures of gene regulator promoter cause both organisms proceed different ways of gene regulation and expression. Mouse is simple model to study development of muscle stem cells. The morphology and genetic data from simple model are easily to analyze. The clues from mouse model provide an important guideline to analyze the complicated and many uncertainties of muscle stem cells development in higher organisms. Lastly, it is to note that HPSCs are nonadherence cells whereas muscle cells in adult of human are adherence cells. During the early development of immature muscle cells in fetus, cell behavior and genetic regulation are almost the same as HPSCs. However, muscle cells become adherence, mature and functioning during attending adulthood.

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