|Place of birth|
|Date of birth||03.09.1980|
PhD in Medicinal Chemistry; TUD, Darmstadt. AK: Prof.
|2004/2005||B.Sc in Medicinal Chemistry; KTH, Stockholm.|
|2003/2004||M.Sc in Organic Chemistry; Ecole Polytechnique, Paris.|
|1998-2003||B.Sc Chemical Engineering; KTH, Stockholm.
Although amyloid proteins feature each a unique amino acid sequence, they all share very similar ultrastructural and physicochemical properties. Inclusions of amyloid proteins in the brain are associated with diseases such as Alzheimer’s disease, Parkinson’s disease and Creutzfeldt-Jakob disease. The hallmarks of AD are Senile Plaques (SPs) and Neurofibrillar Tangles (NFTs). However, both SPs and NFTs occur in over one hundred different related diseases. Therefore, a tremendous value would be added, both for diagnosis and treatment, to a ligand that selectively binds to one form of these amyloidic lesions only.
Efforts to develop imidazo[1,2-a]pyridines (IMPYs) as radiotracers for amyloid imaging have generated several lead compounds. E.g. [123I]IMPY, [18F]FPM-IMPY, and most recently [11C]MeS-IMPY. All these IMPYs have shown to rapidly cross the blood brain barrier (BBB) and bind to their target with high affinity.
We conducted a structure and activity relationship study of over 30 IMPYs on the following proteins: tau-PHFs, Ab oligomers, Ab1-42 fibrils, g-secretases, a-synuclein and prion protein. Furthermore, we performed histochemical staining of plaques and tangles on human post mortem brain slices. This unique, parallel approach, allows for a comparative study of the ligands binding mode onto each protein – providing crucial information for developing a selective ligand for diagnosis and treatment.
Today, a postmortem diagnosis of Alzheimer’s disease is relied on the accurate quantification of its hallmark proteins – amyloids and tangles. On staining with hematoxylin and eosin, amyloid stains no differently from many other proteins. The amyloid proteins’ specific underlying organization affords various staining procedures for their detection, for example with Congo red, silver, thioflavin-S, and immunohistochemical staining techniques.
Common drawbacks of these methods are nonspecific binding, stain variability, tissue damage, and the amount of time required for the procedure. We are developing several new histochemical dyes that can reveal either amyloids or tangles selectively under a fluorescence microscope. Furthermore, these molecules follow Lipinski’s rule of 5 thus have high probability to cross the blood brain barrier, allowing for both in vitro and in vivo monitoring of amyloid and tangles.