Christian Hölscher, PhD

JAD profile

Affiliation(s): 

henan university of chinese medicine

Lab URL: 

http://www.christian-holscher.info

ORCID URL: 

https://orcid.org/0000-0002-8159-3260

Areas of Interest: 

drug discovery, growth factors, synaptic plasticity, animal models in Alzheimer's Disease

Biography & Research: 

My research is focused on neurophysiological and pathophysiological processes in the brain, and to analyse the neurodegenerative mechanisms that underlie progressive neurodegenerative diseases. A main research topic is on the recently described connection between type 2 diabetes and neurological disorders such as Alzheimer’s disease. Several novel GLP-1 incretin analogues developed to treat type 2 diabetes have shown impressive effects in reducing degenerative symptoms in animal models of Alzheimer’s and Parkinson’s disease. These mouse models recapitulate aspects of the human disease, such as memory loss, synaptic loss, loss of synaptic plasticity, reduced energy utilization of neurons, mitochondrial dysfunction, and chronic inflammation in the brain. Techniques employed include work with transgenic mice that express mutated human genes, in vivo electrophysiology, behavioural testing, histology, biochemical analysis of biomarker levels, and cell culture work. Five patents have been submitted to cover the use of these peptides in neurodegenerative diseases, three have been granted in different countries. Several preclinical models of Parkinson’s disease have been established in the labs in the UK and in China, and promising drug candidates are being tested such as novel dual GLP-1/GIP receptor agonists that are superior to the presently used GLP-1 mimetics. I have developed novel dual GLP-1/GIP receptor agonists that are superior to older ones and that have been designed to cross the blood-brain barrier. Patents have been submitted to cover the IP of these molecules. Clinical trials First clinical results showed good protective effects of the GLP-1 mimetic exendin-4 in Parkinson’s patients. Based on the very encouraging results from my lab, several clinical trials have started. A phase II clinical trial to test the GLP-1 analogue liraglutide in Alzheimer patients (ELAD study) has finished and first results show an improvement in cognitive tests (ADASexec test battery). In addition, MRI brain scans showed that brain shrinkage was much reduced. This trial took place in collaboration with Imperial College London at 16 different trial centres in England and is funded by several charities such as the Alzheimer’s Society. Another clinical trial has started at the Cedars-Sinai hospital in Los Angeles to test liraglutide in patients with Parkinson’s disease, funded by the Cure Parkinson’s Trust and the Michael J Fox Foundation, dure to finish 2021. A third trial testing the GLP-1 mimetic lixisenatide has started in 2018, to be conducted at a clinical trials network in France. A fourth trial testing semaglutide in Parkinson’s patients will finish in 2023. Further trials are in preparation.