Autoimmune diseases (3)
Monoclonal antibodies, marijuana, parasitic worms
Anna Petrenko, Copper News
The first part of the article is here.
The fundamental principle of "primum noli nocere" (first of all, do no harm – VM) is directly applicable to the treatment of autoimmune diseases. Although some strategies can be quite successful, their side effects are unpleasant and sometimes dangerous. Many developments never reach the stage of clinical research.The story of many defeats and one luck can be read in the review of Development of therapies for autoimmune disease at Stanford: a tale of multiple shots and one goal by Lawrence Steinman.
The author talks about a variety of strategies for the treatment of autoimmune diseases that have not been crowned with complete success, and about the creation of a humanized monoclonal antibody natalizumab. This drug is now used to treat multiple sclerosis and Crohn's disease.
Despite the obstacles on the way to safe and simple therapy, with the development of science and technology, new and more effective methods of treatment are emerging. It remains to be hoped that in the very near future it will be possible to name many autoimmune diseases undergoing complete cure.
Modern treatmentOne of the directions of traditional treatment is to compensate for what the body lacks due to the disease.
This category includes, for example, thyroid hormones in Hashimoto's thyroiditis, vitamin B12 in autoimmune gastritis or insulin in type I diabetes mellitus. Such therapy relieves the symptoms of autoimmune disease. In addition, blood transfusions can be carried out if the disease has affected the hematopoietic system, and physiotherapy for movement difficulties and problems with joints, bones, muscles.
The main treatment is directed, of course, at the immune system itself. First of all, these are immunosuppressants – substances that suppress the activity of the immune system. Sometimes this leads to serious immunodeficiency, due to which the patient may even catch life-threatening infections. In addition, their use is very prolonged or even chronic. In some cases, anti-inflammatory drugs are prescribed. In addition, other active substances are also used, for example, TNF-α (TNF-α) blockers or T-lymphocyte differentiation.
Developments are shifting from general immunosuppression drugs to immunomodulation by introducing cytokines, for example, interferon and glatiramer acetate. In the case of multiple sclerosis, these drugs already work.
Antigen-specific therapyOne of the safest options is considered to be selective exposure to those immune cells that directly control the autoreactive immune response.
Their removal or modification can even lead to recovery. This approach is used in antigen-specific therapy. This method has long been used in allergy therapy. It allows you to selectively influence some CD4+ T lymphocytes, since it targets their surface receptor - TCR, which recognizes its own antigens or allergens.
Antigen-specific therapy has already shown its success in animal studies and is now being studied in works involving humans. For example, oral antigen-specific therapy for rheumatoid arthritis allows to modulate the T-cell response: patients are injected with a peptide from DnaJ, a heat shock protein that is similar to the "general epitope", and this shifts the production of cytokines from a pro-inflammatory response to a regular one.
VaccinesMany treatment strategies are still in development, but the results are already encouraging.
Special "vaccines" are being created that could reduce symptoms or even cure some autoimmune diseases.
In 2014, researchers from the Perelman School of Medicine at the University of Pennsylvania developed a fast-acting "vaccine" that reverses myasthenia gravis in rats. The disease can occur due to the production of autoantibodies to the acetylcholine receptor (AChR), which plays a key role in neuromuscular transmission.
In June of this year, the FDA approved phase II clinical trials of the Calmette-Guerin vaccine (BCG) for the treatment of type 1 diabetes mellitus. BCG is usually used to prevent tuberculosis, now bladder cancer has been added to this. Earlier in the first phase of studies, it was possible to obtain a statistically significant response to BCG. As scientists say, this time their goal is to get a stable long–term response to the vaccine, and in the future – to cure long-term diabetics. The tests were conducted on the basis of the Central Massachusetts General Hospital (Massachusetts General Hospital) with the support of the Iacocca Foundation (The Iacocca Foundation). "Talking about treating people, not mice, is incredibly exciting," says Lee Iacocca, founder of the foundation. – I promised my late wife to find a cure for type 1 diabetes. Now my family and I are looking forward to further success and are proud of the chance to support these developments that bring us closer to the goal."
GeneticsThe genetic and epigenetic components also contribute to the development of autoimmune diseases.
For example, at the University of Dundee, Scotland, the signaling pathway of the MyD88 protein associated with inflammatory and autoimmune diseases is being actively studied. MyD88 is part of the innate immune system of the body, it is involved in the fight against infections. Disorders of the interaction of proteins in this signaling network and uncontrolled synthesis of proinflammatory molecules lead to diseases of the immune system.
Researchers believe that by enriching the piggy bank of knowledge about diseases, it will be possible to apply already known substances and methods for some diseases. Among them are drugs that affect epigenetics, for example, HDAC histondiacetelase inhibitors and DNMT DNA methyltransferases. These molecules change the packing density of chromatin and thereby regulate gene expression. They are studied in animal models and even in clinical studies.
Scientists from the University of South Carolina (University of South Carolina) resorted to the use of marijuana to influence epigenetics. It turns out that its main active component tetrahydrocannabinol can suppress inflammation through its effect on histones, proteins involved in DNA packaging. Scientists suggest that marijuana may be effective in the treatment of those autoimmune diseases in which chronic inflammation plays a central role: arthritis, systemic lupus erythematosus, multiple sclerosis and others.
Marijuana is now being successfully used to alleviate the side effects of chemotherapy, chronic severe pain and cachexia in AIDS patients.
Helminth therapy: a parasite doctorDue to the spread of daily hygiene procedures in developed countries, it was possible to cope with frequent infection with parasitic worms - helminths.
On the other hand, an epidemic of immune-mediated diseases has set in in these same countries. There is evidence that links these two facts: people with helminths are less susceptible to immune diseases. "Many people believe that in Western countries there is a link between the increase in autoimmune diseases and the focus on cleanliness," comments Professor Ray Norton from the Monash Institute of Pharmaceutical Sciences. "Because the immune system is no longer attacked by such a wide range of infections as in previous generations."
In experiments, mice infected with parasitic worms were protected from the disease in models of colitis, encephalitis, type I diabetes and asthma. Indeed, it turned out that the colonization of the body by helminths simulates immune responses and normalizes the dysregulation of inflammation. Clinical trials have shown that the presence of helminths in patients reduces the development of ulcerative colitis and Crohn's disease.
It is now believed that infection with helminths can effectively treat many diseases, including multiple sclerosis, psoriasis, rheumatoid arthritis and lupus. This information has prompted some patients with autoimmune disorders to urgently populate themselves with parasitic worms.
Fortunately, scientists are ready to offer an alternative to such an ambiguous solution. They found a molecule with immunomodulatory properties in the body of helminths. which can shed light on the effectiveness of treatment by worms-"doctors". This is the ACK1 peptide - it quenches the immune system response by inhibiting the potassium channel. Researchers have shown that ACK1 is similar to another SHK peptide present in the anemone body. SHK is currently being tested in clinical trials for the treatment of multiple sclerosis.
Dr. Sandeep Chhabra from the Monash Institute of Pharmaceutical Sciences says that the team is going to convert the results of treatment into a pill – it's much safer than swallowing parasitic worms on their own.
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04.09.2015