跳至主要内容

Gene Therapy Improves Metabolic Liver Disease Outcome

      

gene therapy.webp

        Scientists at the Mayo Clinic are testing a new approach to correct metabolic liver disorders without a whole-organ transplant. Their findings (“Curative Ex Vivo Liver-Directed Gene Therapy in a Pig Model of Hereditary Tyrosinemia Type 1”) appear in Science Translational Medicine.

In the field of metabolic diseases, we are proud of our portfolio of stable and effective animal models, especially those for Non-alcoholic Fatty Liver Disease (NAFLD). Though popular recently, they still lack effective drug treatment.

         The medical research study tested gene therapy in pigs suffering from hereditary tyrosinemia type 1 (HT1), a metabolic disorder caused by an enzyme deficiency. The common treatment for this disease is a drug regimen, but it is ineffective in many patients, and the long-term safety of using the drug is unknown.

        “Liver transplant is the only curable option in treating HT1, which is characterized by progressive liver disease,” says Raymond Hickey, Ph.D., a Mayo surgical researcher. “Using this novel approach to treat HT1 and other metabolic diseases will allow patients to avoid a liver transplant and save more lives.”

        Through gene therapy, the corrected liver cells are transplanted into the diseased liver, resulting in enzyme production. “This treatment is a new form of cell transplantation that utilizes the patient’s own cells, so it does not require immunosuppressive drugs and, thus, avoids the side effects of those drugs,” adds Scott Nyberg, M.D., Ph.D., a liver transplant surgeon at Mayo Clinic. This therapy resulted in the improvement of pigs with HT1 and the prevention of liver failure. The use of nuclear imaging enables the researchers to monitor expansion of the corrected cells through a noninvasive imaging process.

    “Pediatric patients suffering from inborn errors of metabolism of the liver will benefit most from this therapy,” says Dr. Hickey. “More than one-fifth of all pediatric liver transplants are a result of metabolic disease.”

标签：

评论

发表评论

此博客中的热门博文

What is preclinical testing?

In the process of  preclinical testing  of a compound or biological agent into a drug, the compound involved must go through the testing phase. First, we need to identify potential targets that can treat the disease. Then, a variety of compounds or preparations are screened out. Any compound that has shown potential as a drug for the treatment of this disease needs to be tested for toxicity before clinical testing to reduce the possibility of injury. preclinical testing What is the basis of preclinical testing? According to US Food and Drug Administration (FDA) regulations, a series of tests are required before a new drug is approved for use. In the first stage, basic research determines a hypothetical target for the treatment of a certain disease, and then screens small molecules or biological compounds to discover any substance with the potential to treat the disease. Then, a  preclinical research  phase followed, before which, as described above, the potential toxicity of the compou
发表评论
阅读全文

Inventory of the three major in vitro pharmacokinetic research methods

  The metabolic properties of a compound are an essential factor in whether or not it can be used as a drug in the clinical setting, so pharmacokinetic studies of newly synthesized compounds are required in drug development. In vitro incubation with liver microsomes, recombinant CYP450 enzyme lines, and in vitro incubation with hepatocytes are some of the more common in vitro drug metabolism methods. 1. In vitro incubation method with liver microsomes The metabolic stability and metabolic phenotypes of candidate compounds in different species of liver microsomes are good predictors of the metabolic properties of compounds in vivo. They are practical tools for evaluating candidate compounds in the pre-development phase of drug development. Liver microsomes include rat liver microsomes, human liver microsomes, canine liver microsomes, monkey liver microsomes, and mouse liver microsomes. In in vitro incubation of the liver, microsomes are the "gold standard" for in vitro d
发表评论
阅读全文

Novel Parkinson’s Therapies Possible with New Mouse Model

Parkinson's disease (PD) is a neurodegenerative disorder that is marked by the accumulation of the protein, α-synuclein (αS), into clumps known as Lewy bodies, which diminish neural health. Now, researchers from Brigham and Women's Hospital (BWH) report the development of a mouse model to induce PD-like αS aggregation, leading to resting tremor and abnormal movement control. The mouse responds to L-DOPA, similarly to patients with PD. The team's study (“Abrogating Native α-Synuclein Tetramers in Mice Causes a L-DOPA-Responsive Motor Syndrome Closely Resembling Parkinson’s Disease”) on the use of this transgenic mouse model appears in  Neuron . “α-Synuclein (αS) regulates vesicle exocytosis but forms insoluble deposits in PD. Developing disease-modifying therapies requires animal models that reproduce cardinal features of PD. We recently described a previously unrecognized physiological form of αS, α-helical tetramers, and showed that familial PD-causing missense mutati
发表评论
阅读全文