New thesis about drug discovery targeting non-amyloid pathways in Alzheimer’s disease
Märta Dahlström, PhD-student at the Division of Clinical Geriatrics. On April 30, 2020 you will defend your thesis: "Drug discovery targeting non-amyloid pathways in Alzheimer’s disease", what's the main focus of the thesis?
The main focus of my thesis was to advance drug discovery project within the non-amyloid pathways of Alzheimer’s disease.
Which are the most important results?
We have performed studies within two different areas, the 15-lipoxygenase and its involvement in neuroinflammation and neurotrophin signaling linked to cognitive dysfunctions. We developed a high through-put screening assay and identified potent inhibitors of the human 15-lipoxygenase-1. We studied three NGF mutants and their effect on TrkA signaling, cell survival and cell differentiation. We found that the NGF-R100E mutant, which is linked to a congenital disease HSAN V (patient experience no pain), is more potent than NGF to promote neurotrophic support. We also identified five classes of small molecular compounds that improved NGF and BDNF signaling. Two small molecular compounds were well characterized and displayed positive effects on cognition and depression in rodents. One compound is now in a clinical phase I trial.
How can this new knowledge contribute to the improvement of people’s health?
No cure is available in Alzheimer’s disease, and these approaches to halt or attenuate the cognitive dysfunction found in Alzheimer’s disease could improve the health and the treatment options for Alzheimer’s disease patients.
What´s in the future for you? Will you keep on conducting research?
I have performed my research in a collaboration between Karolinska Institutet and AlzeCure. I plan to continue my research at AlzeCure Pharma AB and my goal is to improve the life quality for the patients.
Alzheimer’s disease is the most common form of dementia. The greatest risk factor for Alzheimer’s disease is advanced age and with increasing life expectancy, the number of people affected by Alzheimer’s disease is estimated to triple by 2050. Alzheimer’s disease is characterized by amyloid beta plaques and neurofibrillary tangles formed in the brain long before clinical symptoms appear. Other pathological alterations found in Alzheimer’s disease include inflammation, neuronal degeneration, mitochondrial dysfunction, altered acetylcholine signaling and decreased neurotrophic support.