Essential tremor (Minor’s essential tremor)

Wat is essential tremor (ES). Familial essential tremor (ES) (hereditary tremor, essential tremor) is a severe neurological disorder in the form of hyperkinesis (violent movements). The disease occurs in middle-aged and elderly people. According to various data, among people younger than 40 years old, essential tremor is observed in 0.3-6.7%, after 70 years - in 8-17%. The disease is hereditary and is caused by gene mutation. According to statistics, this pathology occurs in almost 6% of people. It has been proven that the inheritance of essential tremor has an autosomal dominant type, that is, it is transmitted from parent to child. Clinically, ES is manifested by kinetic and postural trembling of the hands, head, lower jaw, lips, eyelids, vocal cords, less often – legs and torso.

Scientific grounds of our approach: ES belongs to the group of diseases transmitted from generation to generation or through generation, caused by gene or chromosomal mutations. With chromosomal mutations, in some cases, there is a violation of the number of chromosomes (doubling, tripling, absence) or there is a violation of the structure of the chromosome (deletions, inversions, translocations, duplications). With gene mutations, changes are observed, respectively, in the genes on certain parts of the chromosomes. Mutations can involve either a single DNA sequence (simple mutations) or exchanges between allelic or non-allelic DNA sequences. These changes are the cause of monogenic diseases, a group of diseases that is quite heterogeneous in terms of clinical manifestations. The pronounced phenotypic polymorphism leads to variations of clinical signs even in the members of one family. Neurological symptoms can be represented by classic extended forms, a variety of atypical manifestations and inapparent clinical symptoms. When studying the prevalence and outcomes of severe progressive types of ES, we noted that these patients are quite compensated and remain absolutely healthy until a certain time, while the disease debuts at different periods of their lives (in childhood or puberty or at the age of 35 to 60 years) as a result of various etiopathogenetic factors. A person learns about the disease only when it begins to progress and this is the main requirement to be included in our protocol. The patient must have progression of this hereditary disease. In most cases, an avalanche-like increase in degenerative-atrophic processes is formed in various parts of the central nervous system (CNS), leading to pronounced neurological deficit. In some cases, decompensation leads to deep disability due to autoimmune disorders or even to death due to oncological complications. Vital complications are conditioned by the genomic-proteomic structural disorders (deletions, inversions, translocations, duplications) in hematopoietic personalised therapy as a result of DNA damage. Thus, the additional gene mutations lead to profound disability, dementia, or death as a result of autoimmune inflammation, degeneration of the nervous tissue, or carcinogenic degeneration of tissues.

Therapy principle. The special importance of this problem is associated with the lack of effective methods of treatment the progressing ES and the possibility of repeated cases of the disease in subsequent generations. The main hopes in the treatment of ES are assigned on future genomic editing technology. But what do we do today if the disease keeps progressing? Is it possible to stop it? Yes, it is possible; and the answer has been received in our experimental work on the restoration of lethal mutations of damaged cells using the nature-like technology of homologous recombination (equivalent replacement) of mutant DNA with double-stranded DNA (dsDNA) of a healthy donor. Molecular studies of the restoration of lethally damaged cells and MScells with a large number of mutations and damages of DNA caused by 3-5 multiple fatal doses of ionizing irradiation made it possible to develop a revolutionary nature-like innovative biotechnology of restoration and replacement of mutant areas of DNA with analogous parts of healthy donor DNA during the division of the cells. Patient’s own peripheral blood mononuclear cells (PBMCs) and cells are harvested by leukapheresis, incubated with dsDNA of a healthy donor (therapeutic substance approved in the Russian Federation). Part of these restored cells and PBMCs is used for blood infusions, and the other part is used to restore damaged nerve cells of the brain by intrathecal administration of these cells in the spinal canal.

Patient’s own peripheral blood mononuclear cells (PBMCs) and cells are harvested by leukapheresis, incubated with dsDNA of a healthy donor (therapeutic substance approved in the Russian Federation).

Part of these restored cells and PBMCs is used for blood infusions, and the other part is used to restore damaged nerve cells of the brain by intrathecal administration of these cells in the spinal canal.

Result. The technology does not allow to cure all the genetic diseases, especially such complex as ES, and it is not its goal. The technology gives a real chance to arrest the progression of hereditary nervous disease with the nature-like molecular mechanism of the homologous recombination of mutant and damaged pieces of DNA of cells and PBMCs with dsDNA of a healthy donor.

It is able to stabilize the molecular biological structure of the unstable neurons’ genome, block the clonal hematopoiesis in ES patient, as well as compensate for the neurological and somatic state of the patient. The technology is able to prevent the decompensation of various forms of ES in healthy compensated family members with family burden. Harvest of their own cells and PBMCs form a person with HPS family history in a compensated state and, thereby, provides bio-insurance from the possible progression of a hereditary disease in case the disease occurs.