Parkinson’s disease is the second most-common neurological disease, affecting six million people worldwide.
Parkinson’s disease is a progressive disease of the Central Nervous System that affects movement due to decreased levels of dopamine in the brain. Parkinson’s disease is the most common movement disorder. The lifetime risk of developing the disease is 1 to 5 percent. The mean age at disease onset is 60 years and the mean duration of the disease is 15 years. The disease will lead to an increasing social and economic burden on societies as populations age.
Current treatments for Parkinson’s disease are based on increasing the levels of dopamine in the brain. These drugs can’t stop the disease progression and do not affect all symptoms of the disease. Currently there are no disease modifying drugs for Parkinson’s disease on the market.
When the cells that produce the important neurotransmitter dopamine are destroyed, our ability to control the body’s movements is affected. Parkinson’s disease is characterized by rigidity (stiffness of the limbs and trunk), bradykinesia (slowness of movement), tremor of the hands, arms, legs, jaw and face and postural imbalance (impaired balance and coordination).
Tremor is a well-known sign of Parkinson’s. The disease develops gradually, sometimes starting with a barely noticeable tremor in just one hand or symptoms related to rapid eye movement sleep behavior disorder.
Today, it is generally believed that Parkinson’s disease starts many years before the onset of motor symptoms with impaired sense of smell, obstipation or sleep behavior disorder. When motor symptoms appear, 60 to 80 percent of the dopamine-producing cells are damaged, and do not produce enough dopamine.
Parkinson’s disease has an annual incidence of 8 – 18/100,000 person-years and a prevalence of 1 percent in people over 60 years of age. Six million people worldwide are estimated to be affected by the disease. (Lancet. 2016; 388: 1545-1602).
SPECT (Single-photon emission computed tomography) or PET (Positron Emission Tomography) imaging may be helpful to diagnose Parkinson’s disease.
Mutations in the alpha-synuclein gene are causing Parkinson’s disease.
Parkinson’s disease is one of the most prevalent examples of neurodegenerative disorders with alpha-synuclein brain pathology.
At autopsy, widespread nerve cells loss can be seen in the brain stem and neocortex in Parkinson’s disease patients. Soluble aggregates (oligomers/protofibrils) of the alpha-synuclein protein are toxic to nerve cells and lead to the deposits that are a hallmark of the disease.
Alpha-synuclein is mainly located in the presynaptic space in nerve cells and affects the regulation of neurotransmitter release (Burre et al. 2010). In addition, alpha-synuclein can be released from the cell and transfer to nearby cells whereby the disease can spread from one brain area to another (Li et al. 2008). Molecular genetic findings have been crucial to improve our understanding of the disease mechanism.
Differently sized alpha-synuclein oligomers/protofibrils can be detected in the Central Nervous System and increased levels of soluble aggregates, so called oligomers/protofibrils were measured in brains from patients with Lewy pathology compared to brains from non-diseased individuals (Ingelsson et al. 2016).
Oligomers/protofibrils of alpha-synuclein seem to be more prone to transfer between cells and would thereby be responsible for the spread and the propagation of pathology in the affected brain.
Targeting alpha-synuclein oligomers/protofibrils for treatment should thus be an excellent strategy for early therapeutic intervention in Parkinson’s disease and related disorders.
Alpha-synuclein aggregation. Toxic oligomers/protofibrils are the target for BioArctic’s Parkinson’s disease treatment.
Our approach to Parkinson’s disease
BAN0805 offers the potential for an immunotherapy to become one of the first disease modifying treatment for Parkinson’s disease.
BioArctic’s novel treatment concept for Parkinson´s disease is based on removing or inactivating the neurotoxic oligomer/protofibril forms of alpha-synuclein with a humanized monoclonal antibody, BAN0805. Preclinical results show reduced levels of alpha-synuclein oligomers/protofibrils in the central nervous system, less severe motor abnormalities and a doubling of the life-span in Parkinson mice after antibody treatment.
A therapeutically important aspect of BAN0805 is the high selectivity for soluble toxic oligomers/protofibrils forms of alpha-synuclein, thus minimizing interference with the normal physiological monomeric form of alpha-synuclein. The project is based on innovative research by the company in collaboration with Uppsala University, Sweden.
The continued development of the Parkinson’s disease program is conducted in collaboration with the global biopharmaceutical company AbbVie.
The medical need of treatments for Parkinson’s disease is high due to the lack of pharmaceutical agents affecting the underlying pathology. Current treatments are symptomatic and do not halt or modify the disease progression.