Release date: 2018-05-31
In addition to pharmaceutical, biotechnology and medical device companies, gene therapy for rare diseases is also supported by the government.
For example, the National Institutes of Health (NIH) Mutual Fund allocates approximately $200 million to the NIH undiagnosed disease network to accelerate the diagnosis of rare and unknown diseases and the discovery of pathogenesis.
In addition, NIH has launched a treatment program for rare and neglected diseases (TRND), which oversees a series of pilot projects to address specific barriers to the development of gene therapy. In collaboration with biotechnology and academic institutions, TRND hopes to expand the production of genetic vectors and disseminate best practices for regulatory approval of new gene therapies.
Two important platforms
"Genetic treatment of rare diseases is a very exciting strategy," said Dr. Philip J. Brooks of NIH. "Currently, two viral vector platforms are "surfaced" - glands for in vivo gene therapy Related viral AAV and lentivirus lentivirus for in vitro gene therapy involving hematopoietic stem cells."
Recently, at the 2018 Conference on Gene Therapy for Rare Diseases in Boston, Dr. Brooks' optimism was endorsed by Casey a. Maguire, an associate professor of neurology at Harvard Medical School. Dr. Maguire hosted a workshop on current components of AAV vectors, delivery techniques with improved tissue targeting and carrying capacity, and re-dosing strategies to avoid complications of immune response.
Dr. Maguire said his research team is currently involved in a variety of gene therapy applications, including specific diseases such as hereditary deafness and brain tumors, as well as neurological diseases such as Alzheimer's disease and X-linked adrenal leukodystrophy.
Dr. Maguire believes that AAV delivery vectors can be used not only for gene therapy research, but also for the treatment of rare diseases. It has three major advantages: (1) they produce only a slight immune response; (2) different AAV serotypes can be used to deliver genes to multiple types of tissues; (3) they infect dividing and non-dividing cells, but not The genetic material is integrated into the host genome, and the genetic material delivered by AAV usually remains outside the genome, serving the cell as a template for protein transcription.
Rare diseases that can receive AAV delivery gene therapy include aryl acid decarboxylase deficiency, hemophilia A, hemophilia B, and spinal muscular atrophy. AAV technology is also the first direct drug therapy in the United States for diseases caused by mutations in specific genes.
Luxturna is the only platform approved for the treatment of mutations in the biallelic RPE65 gene associated with hereditary retinal diseases. This platform has been used to integrate genetic material into the genome of dividing and non-dividing cells to facilitate cell engineering applications. These vectors also show promise in experimental treatment, including collecting patient stem cells, performing in vitro procedures, and reinjecting them into a patient. This method has been used to treat X-linked severe combined immunodeficiency (SCID), Wiskott-Aldrich syndrome, adenosine deaminase-SCID, and white dystrophy (ie X-linked adrenal leukodystrophy, heterochromatin and Glomerular leukemia).
Genome editing
In November 2017, a patient with mucopolysaccharidosis type II (MPS II, also known as Hunter's syndrome) received Sangamo's SB-913 treatment (phase I/II clinical trial), which is an achievable In vivo gene editing therapy research (ie, the Champion Study) is also the first treatment for Hunter Syndrome to accurately edit cellular DNA in vivo. Dr. Sandy Macrae, CEO of Sangamo Therapeutics, said: "We are at a turning point in the new frontiers of genomic medicine."
SB-913 utilizes Sangamo's zinc finger nuclease (ZFN) genome editing technology and liver-targeted AAV vectors to correct the precise location of genes into hepatocyte DNA. Once the gene is in place in the albumin gene, it produces a stable and lifetime supply of iduronate-2-sulfatase. (If the enzyme is inactivated or deleted due to mutations in the IDS gene, toxic carbohydrates will accumulate throughout the body's cells).
According to a poster by Sangamo at the 2018 World Symposium in San Diego last February, the first two patients treated in the Champion Study responded well to SB-913 treatment.
“So far, no safety issues related to research drugs have been identified.†Dr. Paul Harmatz, principal investigator of Champion Research, pointed out. Dr. Brooks believes that this technology is suitable for the treatment of a variety of diseases. “In fact,†he said, “the goal of the new NIH program is to accelerate the development of genome-based editing therapies.â€
Microdystrophin gene transfer
At the 2018 Conference on Gene Therapy for Rare Diseases, Solid Biosciences' COO Alvaro Amorrortu discussed the strategic decision to scale production of gene therapy. In this presentation, Amorrortu draws on his company's experience in developing treatment for Duchenne muscular dystrophy (DMD). (In a rare disease of DMD, mutations in the dystrophin gene result in low levels of dystrophin, which leads to degenerative muscle disease, and patients rarely live to 30 years of age).
Amorrortu said: "I hope to learn some of the key knowledge from our experience to continuously improve production processes and capabilities in the growing field of gene therapy, especially for the challenging rare genetic diseases of DMD. â€
“From the outset, we wanted to ensure that manufacturing does not inhibit the critical path of drug development, whether it is to successfully provide clinical trials or scale up to meet the needs of the commercial market. This is not always easy, but we think we choose The right path."
In November 2017, Solid Biosciences announced that it has initiated a clinical trial of SGT-001, the company's primary microdystrophin gene transfer candidate for the treatment of DMD. These activities included the administration of the first patient in the I/II clinical trial IGNITE DMD at the University of Florida.
SGT-001 was used on February 14, 2018. A few days later, the patient had a decrease in platelet count, followed by a decrease in red blood cell count and hospitalization for complement activation. “Patients did not show signs or symptoms of coagulopathy (hemorrhagic disease) in the liver function test, nor did they have changes related to baseline levels,†the company said in a press release. “Patients respond well to treatment, and now Asymptomatic."
Solid Biosciences classified the incident as a Suspected Serious Adverse Reaction (SUSAR) and reported it to the FDA. The FDA's response was to suspend the trial. "We are working with the FDA to better understand the unexpected events that led to the clinical suspension and to develop a plan to monitor and manage future events," said Ilan Ganot, CEO of the company.
The company also said it still believes in the potential of SGT-001. Currently, Solid Biosciences continues to focus on its therapeutic portfolio for all aspects of DMD, from its genetic roots to multiple disease manifestations.
Bright future
Researchers involved in genomics research and gene therapy for rare diseases believe that now is the most exciting stage of innovation discovery. According to Amorrortu, “We will eventually see a successful combination of science and commercialization in the treatment of patients in clinical trials. Although this road has been full of ups and downs, patients with rare genetic diseases not only need our continuous efforts, but also It is also worth our continued efforts."
Source: Bio-Exploration
Natural Plant Extract is a kind of solid powder obtained by cleaning, extracting, concentrating and spray drying Chinese herbal fruits and vegetables, without adding any other ingredients; The effective components and essence of plants are extracted, which improves the full utilization rate of plants and is beneficial to human absorption.
The components of plant extracts can be divided into glycosides, acids, polyphenols, polysaccharides, terpenoids, flavonoids, alkaloids and so on. For example, the main component of green tea extract is tea polyphenols. Ginseng extract mainly contains a variety of ginseng monomer saponins; According to different characters, it can be divided into extract, powder, lens, etc., such as violet leaf extract, hang white chrysanthemum extract.
Natural Plant Extract,Paeony Extract,Licorice Root Extract,Dong Quai Root Extract
Fufeng Sinuote Biotechnology Co.,Ltd. , https://www.ffsinuoteplant.com