Polyglutamine diseases are a group of incurable rare genetic diseases that lead to the death of cells in the brain. The most famous Huntington's chorea. It usually affects people aged 35-50, although it may also appear in children as young as a few years old. The disease not only worsens the quality of life, but also shortens it by up to 20 years. What else are polyglutamine diseases? What are the symptoms? What is their diagnosis and treatment?

Polyglutamine diseasesis a group of incurable rare genetic diseases that lead to the death of cells in the brain. These include nine disease entities: ¹

  • Huntington's chorea
  • Spinal-cerebellar ataxia of the following types: 1, 2, 3, 6, 7, 17 (each type is treated as a separate disease entity)
  • Naito-Oyanagi disease (dentatorubral-pallidoluysian atrophy, DRPLA)
  • Kennedy syndrome (X-linked spinal and bulbar muscular atrophy, SBMA, SMAX1)

Polyglutamine diseases - causes

Polyglutamine diseasesare caused by a mutation in a gene. A he althy gene has up to 26 CAG repeats that correspond to glutamine - an organic compound that is a component of protein necessary for living organisms. In people withpolyglutaminediseases, the number of CAG repeats exceeds this number. For example, in Huntington's Chorea, it exceeds 40 repetitions. Information written in a gene, read in the process of transcription and translation, is transcribed into the gene products - RNA and protein. First, transcription produces mRNA that retains information about the increased number of CAG repeats. The final translation of genetic information into a specific protein structure takes place in the process of translation. The protein also retains information about the extended CAG sequence. RNA and protein resulting from the gene are toxic to the cell and disrupt the processes taking place in it. Ultimately, this leads to cell death, which is especially evident in the nervous system.

Polyglutamine diseases - symptoms

  • Huntington's Chorea - manifested by involuntary movements of the chorea and progressive dementia and cognitive decline. As a result, it often leads towasting of the organism and death
  • spinocerebellar ataxia - incl. problems with maintaining balance, both in standing position (rhythmic shaking of the head and torso is observed) and while walking (the patient has difficulties in maintaining the vertical position of the body, his gait is slow, unstable, on the so-called wide base), muscle laxity , frequent and painful muscle spasms,
  • Naito-Oyanagi disease - the disease consists of ataxia (ataxia), choreoathetosis (characterized by episodes of abnormal muscle movements), and dementia. Mental retardation, behavioral disturbances, myoclonus and epilepsy are observed in the childhood form. Corneal epithelial degeneration has also been reported
  • Kennedy Syndrome - Initial symptoms include tremors, tingling muscles, muscle spasms, fatigue, and slurred speech. As the disease progresses, patients develop weakness and atrophy of the limbs and bulbar muscles, manifested by dysarthria, dysphonia, drooping jaw, tongue weakness, difficulty in chewing, and impaired mobility

Polyglutamine diseases - diagnosis

Final diagnosis is made on the basis of a genetic test. The waiting time for the results is 10 - 14 days. The test is not reimbursed and its price is about PLN 500.

Polyglutamine diseases - treatment. RNA research is a new hope for patients

Finding a therapist to stop or delay polyglutamine diseases is difficult for several reasons. The problem is, among others the genetic basis of the disease, and scientists are not yet able to effectively "repair" genes in all cells of an adult organism. In addition, the disease primarily affects the nervous system, the availability of which to drugs is limited by the presence of a physical barrier that separates the blood from the brain. In many cases, there would be a need for direct dosing of drugs into the brain, which is very dangerous. Scientists can name and locate genes responsible for polyglutamine diseases, but they have not yet understood the mechanisms of their formation. This task was undertaken by a research team from the Institute of Bioorganic Chemistry of the Polish Academy of Sciences in Poznań. Martyna Urbanek, M.Sc., a scholarship holder of the L'Oréal Polska For Women and Science program, conducts research on nuclear RNA clusters in cell models of polyglutamine diseases as part of her doctoral dissertation.

According to an expertMartyna Urbanek, PhD student at the Department of Molecular Biomedicine of the Institute of Bioorganic Chemistry of the Polish Academy of Sciences in Poznań

My research shows that the product of a damaged gene - RNA - has a role in the pathogenesis of diseasepolyglutamines, inter alia, through the formation of the mentioned RNA clusters. This shows that the proposed therapy must take into account both gene products - RNA and protein - and not only the damaged protein, as previously postulated. By removing only the damaged protein, we would only eliminate part of the cause of the disease and thus part of the symptoms. The ongoing work also includes the possibility of removing RNA clusters, which could be part of the therapy

Bibliography:

1. Dubas-Ślemp H., Tylec A., Michałowska-Marmurowska H., Spychalska K., Huntington's disease - a neurological or psychiatric disorder? Case report, "Psychiatria Polska" 2012, volume XLVI, number 5

The article uses the materials of the creators of the L'Oréal Polska For Women and Science program

Category:

Genetic diseases