Parkinsonism: a work plan

Parkinson's disease is a slowly progressive disease that impairs mobility, muscle control and a sense of balance. Over the past 20 years, researchers have delved very deeply into the processes involved in the degeneration of nervous tissue in this disease. In a review published in the Journal of Parkinson's Disease, experts discuss the latest advances in this field, including the identification of the main genetic risk factors, the development of the most representative animal models of the disease, successful preliminary results of the use of antisense oligonucleotides and vaccines for other neurodegenerative diseases, as well as a wide range of repurposed drugs that have demonstrated potential effectiveness and are at different stages of clinical trials.

According to the authors, slowing the progression of Parkinson's disease is a "holy Grail" for researchers. Looking to the future with hope, they identified several promising developments, which are listed below.

• new therapeutic targets identified in accordance with open genetic risk factors, such as autosomal dominant mutations of the LRRK2 gene, as well as the enzyme glucocerebrosidase (GCase), the level of which is reduced in patients with GBA gene mutations. In the latter case, ambroxol, currently licensed for use in cases of pulmonary surfactant deficiency, proved to be effective.
• targeting the "non-motor" manifestations of Parkinson's disease, such as disorders of cognitive function, speech, gait, as well as difficulties with maintaining balance and vegetative insufficiency, which often precede the manifestation of motor symptoms and can be used as signals to initiate therapy, potentially capable of slowing or stopping the development of the first motor manifestations of Parkinson's disease.
• therapy with glucagon-like peptide-1 (GLP-1) receptor agonists licensed as a drug for the treatment of type 2 diabetes mellitus and demonstrated neuroprotective properties on a whole spectrum of animal models of Parkinson's disease, including two alpha-synuclein models. Currently, a phase 3 clinical trial of exenatide is planned and there is a growing interest in studying other drugs of this class for potential therapeutic properties in relation to Parkinson's disease.
• repurposing of drugs used in the treatment of various diseases, such as biliary primary cirrhosis of the liver and chronic myelocytic leukemia, as well as beta-adrenergic receptor agonists (salbutamol, clenbuterol).
• the use of immunomodulatory therapeutic approaches to prevent or slow the progression of the disease, including azathioprine and sargramostine.
• and in conclusion, the authors mention the prospects for the use of nanotechnology: "a grand breakthrough would be the development of a therapy that could provide an accurate effect on alpha-synuclein pathology, the dissolution of toxic aggregates and a shift in equilibrium towards normal monomeric alpha-synuclein."

According to the authors, today specialists are already better versed in the processes involved in neurodegeneration in Parkinson's disease, and, accordingly, have greater confidence that laboratory data and positive results of early clinical trials will eventually be transformed into therapeutic approaches that slow down the progression of Parkinson's disease. Currently, there are no drugs with a proven ability to slow the progression of this disease. Demonstrating the success of one or more experimental methods will trigger changes in the system of working with patients. And fruitful cooperation between researchers from different countries significantly accelerates the process of developing agents that can slow down, stop or even reverse the progression of Parkinson's disease.

Article by Tom Foltynie et al. Therapies to Slow, Stop, or Reverse Parkinson's Disease is published in the Journal of Parkinson's Disease.

Evgenia Ryabtseva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of IOS Press: The search for the holy grail: Promising strategies for slowing, stopping, or reversing Parkinson's disease.