OLIGOFASTX follows with great interest all the recent advances in the work with oligonucleotides, not only in terms of new lines of research, but also with respect to all the applications that are being developed close to the market. Because it is our ultimate goal and our objective: to provide solutions to diseases that do not have them.
Osteoporosis and premature aging in children are two diseases that could soon have solutions, thanks to the research work in the area of oligonucleotides that is being developed in different scientific fields. As for hepatitis B, work is being done in the area of prevention, which will undoubtedly help to curb the increase in the number of cases worldwide.
Oligos against osteoporosis
Osteoporosis is increasingly present worldwide and is mainly associated with the sex and age of the population. The annual incidence (number of new cases per year in the world population) is considered to be 1% in women aged 65 years, 2% in women aged 75 years and 3% in women over 85 years. In the case of men over 50 years of age, the incidence is 0.5-0.7%, which is less than half that observed for women.
For some time now, several avenues of research have been opened in order to slow down the destruction and even regenerate bone mass. Research in the field of oligonucleotides opens a hopeful horizon.
Scientists from several German centers have designed an oligonucleotide with antagonistic activity of miRNA-19a/b, a microRNA whose levels are elevated in the bone of patients with bone loss and in mice with osteoporosis. After demonstrating that inhibition of miRNA-19a/b by this oligonucleotide induces the differentiation of osteoblasts (bone “generating” cells) in vitro, the scientists carried out in vivo experiments on animals receiving a weekly intravenous dose for 28 days, after which an increase in trabecular bone mass in the spine and in regions of the femur and tibia was observed, as well as an increase in cortical density in the latter bone.
The experimental treatment also improved several osteogenic parameters, such as the number of osteoblasts per unit of bone surface area and the degree of osteoblast activity. In contrast, the same parameters remained unchanged in osteoclasts, or bone degrading cells.
Premature aging in children, under the microscope
An international research team led by King Abdullah University of Science and Technology (Saudi Arabia) has identified a new target to treat syndromes that cause premature aging in children.
The so-called progeroid syndromes are a group of rare genetic disorders that cause signs of premature aging in children and young adults, such as Werner syndrome and Hutchinson-Gilford progeria syndrome.
This aging is characterized by the progressive loss of nuclear architecture and by an underlying tissue-specific genetic program, but the causes are still unknown. Now, this research, published in the scientific journal ‘Science Translational Medicine’, has identified a promising new target to treat these syndromes by preventing the loss of nuclear architecture.
The target is called long interspersed nuclear element (L1) RNA, a family of repeated sequences that comprises 17 to 20 percent of the mammalian genome and whose functions are largely unknown. These sequences are kept inactive by the tightly packed DNA architecture called heterochromatin. Sequencing analyses demonstrated increased L1 RNA expression in cells taken from patients with progeroid syndromes.
Subsequent tests showed that this increased L1 RNA expression was responsible for the inactivation of an enzyme, called SUV39H1, which caused the loss of heterochromatin and the changes in gene expression that cause cellular aging. The researchers were able to block L1 RNA expression and reverse the aging process in cells taken from patients with progeroid syndromes and in mice genetically modified to simulate premature aging.
Oligonucleotide treatment to prevent chronic hepatitis B
Hepatitis B is a viral infection of the liver that can lead to both acute and chronic disease.
Hepatitis B virus is most commonly transmitted from mother to child during childbirth, as well as through contact with blood or other body fluids during sex with an infected partner, injections without sufficient protection against risks, or exposure to sharp instruments during health care or in community settings.
WHO estimates that 296 million people had chronic hepatitis B virus infection in 2019, with 1.5 million new infections occurring each year.
Research work on this disease in the field of oligonucleotides is focused on prevention. Thus, Bepirovirsen, an antisense oligonucleotide therapy, helped in the long-term prevention of chronic hepatitis B in patients with and without nucleoside/nucleotide analogues in a phase II trial.
GSK has announced results from its Phase IIb study (NCT04449029) of bepirovirsen for the treatment of chronic hepatitis B (CHB), indicating that antisense oligonucleotide therapy could help treat CHB alone or in combination with nucleoside/nucleotide analogs (NAs).
Bepirovirsen demonstrated long-term hepatitis B surface antigen (HBsAg) and hepatitis B virus (HBV) DNA clearance in patients receiving concurrent treatment with NAs and those not receiving NAs. Current treatment of the disease includes NAs, which are often taken for life because of their ability to suppress the virus.
We keep a close eye on everything that happens around the world of therapeutic oligonucleotides to gather the advances and transfer them to our blog.
Header image: https://www.nationalgeographic.com.es/medio/2019/08/20/osteporosis-en-4-fases_f4146f58_1280x720.jpg