Schizophrenia is a chronic and severe neurological disorder which disorients an individual’s perception of reality. Consequently, this affects how patients think, feel, and behave. Currently, schizophrenia affects 1% of the world’s population. Two major symptoms that characterize this disease includes hallucinations and delusions. However, other symptoms include disorganized thinking and speech, irregular motor movement, and limited emotional expression. These symptoms can become severe and significantly impact a patient’s ability to perform daily functions, such as work, social interactions, and self-care. In many cases, patients have trouble with their focus, memory, and critical thinking skills. Risk factors include genetic family history of schizophrenia, neurological imbalances, trauma, other stressful life events, and substance use. However, the exact cause of schizophrenia is not completely understood. Patients are diagnosed after a series of comprehensive psychiatric evaluations including interviews and assessments of symptoms.
Unfortunately, there is no cure for schizophrenia. However, there are medications to mitigate symptoms. Antipsychotic medications help manage neurological features while psychotherapy can help develop coping mechanisms and improve social and emotional skills. There are also services offered for supportive housing with vocational training for patients. Scientists around the globe are working to develop effective therapies that can prevent or improve cognitive deficits in schizophrenic patients.
A recent article in Nature, by Dr. Philippe Rondard and others, developed a therapy that can correct cognitive deficits in patients with schizophrenia. Rondard is a team leader and researcher at the Institute of Functional Genomics in France. His research focuses on pharmaceutical drugs for neurological disorders, such as schizophrenia. They also investigate specific proteins that interact with neurotransmitters and learn how these proteins can be leveraged to modulate neurological and psychiatric diseases.
Rondard and his team designed a nanobody generated from llama antibodies, which target the glutamate receptor that regulates neural activity. Nanobodies are small parts of antibody fragments that are commonly derived from llamas or alpacas. They tend to be very stable and soluble, which penetrate tissues for effective therapeutic treatment. Interestingly, the therapy is administered via veins or muscles and can pass through the blood-brain barrier. This is a major accomplishment because the blood-brain barrier is an extremely selective biological barrier that protects the brain. It is often very hard to develop a therapy small enough to pass through and have an effect. As a result, these nanobodies are able to sufficiently reach brain receptors and mitigate neurological pathogens.
The nanobody therapy was evaluated using two different preclinical models of schizophrenia. Specifically, this therapy was tested in mice and was found to correct the cognitive deficits amongst the two different mouse models. Mouse modeling works to reflect similar pathologies in humans and is critical for the development of pharmaceutical drugs. Currently, the team is working to conduct clinical trials in human patients with schizophrenia. This work introduces nanobodies as a new therapeutic strategy necessary to effectively act on the brain to improve deleterious symptoms. The team hopes to extend this to other neurological disorders. As a result, this work provides an alternative option for patients that experience schizophrenic symptoms and can improve quality of life.
Article, Nature, Philippe Rondard, Institute of Functional Genomics
