Gene therapy in the treatment of osteochondrosis and herniated intervertebral discs


Areas of application of growth hormones

The scope of application of somatotropin preparations is extensive, it includes the following conditions:

  • Destruction (destruction) of joints. Many diseases of the musculoskeletal system are associated with the destruction of joints, due to which their mobility significantly suffers and pain appears. Growth hormone starts regeneration processes, improving the condition of joints, returning a person to their former mobility. The positive effect has an evidence base.
  • Healing after fractures. When a bone is fractured, not only the bone tissue is affected, but nearby ligaments are often affected, and joints may also suffer. Treatment of the fracture itself requires a professional medical approach, but the use of somatropin drugs will significantly speed up recovery.
  • Sprains and microtraumas. For athletes and even ordinary people, sprains are one of the most annoying problems. Bone and muscle tissue are restored much faster than the ligamentous apparatus. And if some fibers have been damaged, then recovery will take a long time. Growth hormone allows you to recover much faster.
  • Healing of burns. Recovery from burns of any severity depends entirely on the ability of human tissue to regenerate. Depending on the depth of the lesion, the body has to replace from the superficial layers of skin to muscle tissue. Enhanced regeneration is one of the key effects of growth hormone
  • Recovery after cosmetic surgery. Despite the fact that cosmetic surgeries are carried out quickly and with minimal trauma, they also require a recovery stage. The use of somatotropin preparations allows the process to be accelerated. The hormone also strengthens the body's defenses.

Gene therapy in the treatment of osteochondrosis and herniated intervertebral discs

According to genetic studies, degenerative-dystrophic changes (osteochondrosis) of the spinal column can be traced in three generations in approximately 94-95% of patients complaining of regular back pain. The remaining 5-6% pass on pathological abnormalities through a generation. At the same time, many experts are unanimous in the opinion that the disease initially affects the nucleus pulposus of the intervertebral disc, and then its shell and nearby soft tissues.

The mid-90s of the last century were marked by the intensive development of molecular biology, genetics and tissue engineering. This gave impetus to the study of the influence of growth factors on intervertebral disc cells. In recent years, a large number of experimental and clinical studies have been devoted to genetic treatment and biological regeneration of tissue of the affected intervertebral disc.

Since today almost all conservative and surgical methods of treating intervertebral hernias are already known, supplemented and improved, it is difficult to imagine any revolutionary discovery in this area. At the same time, studying the possibilities of gene therapy, especially in combination with minimally invasive surgical methods, is quite interesting, effective and promising, as it provides the opportunity not only to stop the progression of degenerative processes, but also to regenerate the intervertebral disc.

Anatomy

Degenerative-dystrophic changes in intervertebral discs begin with biochemical and morphological abnormalities in the body, and end with disturbances in the biomechanical properties of the affected spinal motion segment.

In a normal healthy state, the intervertebral disc consists of a cartilaginous matrix, which is divided into the nucleus pulposus, which contains chondrocytes and the annulus fibrosus, which contains fibroblasts. The condition of the matrix ensures the shock-absorbing and biomechanical qualities of the disc. At the same time, cells located within one or another fibrocartilaginous structure produce and maintain the vital activity of the matrix.

The matrix of the intervertebral disc is a kind of frame made of macromolecules, the main components of which are collagen and proteoglycan. Collagen is responsible for the shape and elasticity of the matrix, and proteoglycans are responsible for the elasticity of tissues and its resistance to mechanical stress (compression, stretching, etc.). Macromolecules are able to attract and retain water and essential nutrients.

The annulus fibrosus of the intervertebral disc contains approximately 70% collagen proteins, and the nucleus pulposus contains only 20%. At the same time, the maximum concentration of proteoglycans (more than 50%) is observed in the nucleus pulposus. With the development of osteochondrosis in the intervertebral discs, the matrix of the nucleus pulposus is replaced by fibrous tissue (the chondrocytic phenotype is replaced by fibrous).

Disc degeneration

Morphological changes in intervertebral discs occur from a certain age. They begin with dehydration and loss of integrity of the nucleus pulposus, then cracks form in the fibrous walls and endplates adjacent to the vertebral bodies

At the molecular level:

  • the diffusion of water, trace elements and nutrients, enzyme activity and cell viability decreases;
  • areas of apoptosis (cell breakdown products) and degraded matrix cells accumulate;
  • The synthesis of proteoglycans decreases and collagen redistribution occurs.

In addition, a huge number of inflammatory mediators are usually identified in the affected intervertebral disc. Among them: nitric oxide, fibronectin, interleukins, prostaglandins, tumor growth factors, matrix metalloproteinase and others. Each of the mediators takes its place in the development of pathology.

For example, nitrogen, interleukin and prostaglandin are direct inhibitors of proteoglycan synthesis. An inhibitor is a substance that suppresses or slows down the course of physiological or physicochemical reactions. Thanks to interleukin, a protrusion is formed, then a herniation of the intervertebral disc, and pain occurs. Nitrogen, metalloproteinase, and tumor growth factors make the spinal roots more sensitive to compression.

Thus, an imbalance in the synthesis, breakdown and accumulation of macromolecules of the cartilage tissue matrix negatively affects its quality and integrity, as well as the biomechanical properties of the intervertebral disc itself. An important role in the formation of intervertebral hernias is played by genetic risk factors - polymorphism of the vitamin D receptor gene, which can cause the occurrence of other degenerative diseases of the spine (osteoporosis, arthrosis, arthritis, etc.).

Genetic treatment

The main tactics of conservative therapy and surgical intervention for herniated intervertebral discs are aimed at reducing the severity of clinical symptoms of the disease and do not in any way affect the pathogenetic factors in the formation of degenerative processes. Biological manipulations are more promising in this regard, since they allow not only to slow down the progression of the disease, but also to partially regenerate the affected cartilage tissue.

The ability to treat degenerative diseases of the spinal column at the molecular level has expanded significantly with the successful research into the therapeutic effects of genes and cell growth factors. The essence of the method is based on the transfer (transfer) of genetic material (DNA or RNA) into the necessary cell for the development (production) of the necessary therapeutic agent. Transfer is especially effective in the treatment of congenital genetic pathologies that are determined by errors in one of the genes.

To transfer (transport) the necessary genes, “vectors” or carriers are used, which can be divided into: viral and non-viral.

Viral carriers perform their role well: they efficiently transport genetic material directly into the cell, take over DNA replication and transcription.

Viral vectors are divided into:

  • Retroviruses carry RNA and are incorporated into the recipient's genome (effectively transferring the desired gene to the recipient's chromosomes).
  • Adenoviruses carry DNA and can carry 4 times more genetic material than retroviruses, but they have a fairly short expression time (the lifespan of the recipient cell). In addition, adenoviruses produce an immune response, so they can only be used once.
  • Adeno-associated or porvoviruses integrate their own DNA into guest chromosomes. They are able to penetrate non-dividing cells, but carry very little genetic material and are difficult to produce.

To facilitate the transfer of the necessary genetic code into the target cell, non-viral carriers additionally use physicochemical substrates. These vectors, unlike viral ones, are chemically more stable, carry large volumes of genetic material, do not cause an immune response, and can be administered repeatedly. The disadvantage of their use is the rather low efficiency of transfection (introduction) of the required material and the short duration of expression.

Non-viral vectors are divided into:

  • Plasmids are free DNA structures that carry genes necessary for bacteria to produce resistance to antibiotics. This vector is not accepted by all recipient cells, so the plasmids are combined with a special shell.
  • Cationic liposomes carry a large volume of essential DNA and are introduced into the guest cell by “sticking” to its membrane.
  • DNA ligands consist of protein and DNA complexes that are perceived by cell membrane receptors. After the protein part is connected to the membrane of the target cell, the DNA is transferred into it by phagocytosis.
  • The principle of a gene gun is based on the penetration of tiny metal particles coated with a thin coating of genetic material (DNA) into the recipient cell. Metal particles are accelerated using electric current or pressure.

Methods of introducing genes

There are two ways to introduce genetic material into recipient cells:

  • In vivo (translated from Latin as “inside a living organism”), in which therapeutic genes are introduced directly into the body. Basically, the technique involves the use of adenoviruses.
  • Ex vivo (translated from Latin as “from life” or “outside a living organism”) is a more complex method. Its essence lies in a biopsy of the recipient's cells, their reproduction, transfer of the necessary gene material into the cellular structure, after which the cells produce a therapeutic agent. Next, the updated cellular structure is implanted back into the body. The technique is more complex, time-consuming, expensive, but safer, since there is no direct contact of the body with viruses or free DNA strands. In addition, when genes are expressed in this way, doctors are able to track and control the resulting therapeutic gene, as well as effectively integrate it into the chromosomes of the recipient's proliferating and developing cells.

After a series of successful experiments on animals, in 2000 a transfer was carried out with cells from the human intervertebral disc (nucleus pulposus). An adenoviral vector and growth factor were used for transfer. As a result, the same level of expression was noted in both affected and degenerative intervertebral discs, which indicates the possibility of treating any stage of the disease.

Further, a significant surge in the synthesis of collagen and proteoglycans, mineralization of the cartilage and bone matrix, and regeneration of intervertebral tissues were observed.
Thus, gene therapy, especially in combination with minimally invasive surgical methods, is a promising direction in the treatment of osteochondrosis and vertebral hernias. Author: K.M.N., Academician of the Russian Academy of Medical Sciences M.A. Bobyr

Which doctor should I contact?

If a person has complexes about his height and wants to increase it, then first of all it is necessary to consult a doctor to find out whether there are drugs for increasing height that are suitable specifically for him, whether surgical intervention is possible, etc. Any drugs, hormonal or not, should be taken only after consultation with a doctor, who will examine the patient’s medical history and make a conclusion about the advisability of their use.

I, Georgy Nikitich Romanov, am a qualified endocrinologist with more than 20 years of experience. My area of ​​expertise is the endocrine system and hormones. In my practice, there were patients with growth problems, and we solved them using effective modern methods. I have classical and modern knowledge in the field of medicine, I consider each patient as a separate unit, thoroughly study the history and draw conclusions based on it and a number of diagnostic studies.

At the moment, I provide face-to-face consultations in a private clinic in Gomel, as well as paid online consultations, which you can sign up for directly in any of my accounts: Viber, Skype, Instagram, Vkontakte, WhatsApp.

As part of an online consultation, I can evaluate diagnostic results, study symptoms and refer you for the necessary examinations, adjust treatment, and more.

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