The disease
Parkinson’s disease is a neurological disorder that primarily manifests with motor symptoms such as tremors, imbalance, and muscle rigidity. However, non-motor symptoms also exist and typically emerge years before the onset of motor symptoms. The condition is characterized by the gradual deterioration of dopamine-producing neurons, resulting in a deficiency of this neurotransmitter in the brain, which primarily gives rise to the symptoms. Unfortunately, there is currently no cure that can alter the disease’s trajectory. Current treatments only aim to manage both motor and non-motor symptoms to enhance the patient’s quality of life. Consequently, there is an urgent need for a therapy that can halt the disease’s progression.
The target
Neuron degeneration in Parkinson’s disease is primarily associated with the aggregation and accumulation of a protein called alpha-synuclein. These aggregates form insoluble fibrils, which are a hallmark of the disease and are commonly referred to as Lewy bodies. Alpha-synuclein aggregates disrupt the normal functioning of cells, ultimately leading to their death. Recent research suggests that alpha-synuclein aggregates may also contribute to non-motor symptoms, including cognitive impairment, sleep disorders, and depression. Therefore, targeting these toxic aggregates is a promising approach for developing new treatments that can halt or slow the progression of Parkinson’s disease.
The strategy
Our body naturally produces antibodies to fight infections. These antibodies are unique, and each one can recognize a specific foreign molecule or antigen. One of our approaches at CEREBRO Therapeutics consists of developing a therapy utilizing the antigen binding region of an antibody against the protein alpha-synuclein. This protein is found in the brain and is believed to cause Parkinson’s disease when it accumulates in large amounts. Normally, antibodies are too big to get efficiently into the brain when they are administered into the bloodstream. Consequently, large quantities must be administered, which can result in undesirable side effects. In our pursuit of a non-invasive therapy, we have created smaller antibody versions called single-chain variable fragment (scFv). These “mini-antibodies” are five times smaller than the full size antibodies and the corresponding synthetic mini gene encoding them can be inserted into a viral vector to facilitate their delivery to the brain. The viral vector is non-infectious and serves only as a carrier to transport the scFv-encoding gene into the brain cells. Once it has reached its destination, the mini-antibody produced by these cells can bind to alpha-synuclein, thereby preventing its aggregation and halt the progression of Parkinson’s disease.
