ABAD INHIBITORS – NOVEL THERAPEUTIC STRATEGY TO TREAT ALZHEIMER’S DISEASE

 

ABAD inhibitory AD

Technology Owner
University Hospital Hradec Králové
University Hradec Králové
University of St. Andrews

Inventors
Kamil Musilek, Ondrej Benek
Kamil Kuca, Ondrej Soukup
Daniel Jun, Laura Aitken
Frank J. Gunn-Moore
Terry K. Smith, Patrick Guest

IPR Status
CZ patent No. 305633

Stage of Development
In vitro validation

Contact
Lucie Bartošová
lucie.bartosova@fnhk.cz
+420 727 802 314

ABAD INHIBITORS – NOVEL THERAPEUTIC STRATEGY TO TREAT ALZHEIMER’S DISEASE

Background
Alzheimer’s disease (AD) is the most common cause of dementia in people of 60 years age and older, and accounts for approximately 75% of the total dementia cases worldwide. Disease is accompanied by neuronal death in certain areas of the brain and leads to the modification of metabolism in the CNS. Current therapy is based on the theory of the cholinergic deficit in patients with AD, therefore reversible inhibitors of acetylcholinesterase (AChE), such as e.g., rivastigmine, donepezil and galanthamine are used in therapy. Except AChEI mentioned, memantine is administered, that belongs to the group of antagonists of glutamate (NMDA) receptors. Globally, however, there are efforts to find new medicines for the treatment of AD, because the current treatment is only symptomatic and does not cure the cause of the disease.

Description of the Invention
Amyloid vázající alkoholdehydrogenasa (ABAD) je enzym v nervových buňkách a jejich mitochondriích, který přímo interaguje s amyloidem β, který je jedním z rizikových faktorů při vzniku AD. Díky této interakci se enzym ABAD stává nefunkčním pro likvidaci škodlivých agens ovlivňujících nervové buňky, které po interakci amyloidu β s ABAD zaniknou. Inhibitory ABAD mají za úkol bránit interakci mezi ABAD a amyloidem β, a tak chránit funkčnost nervových buněk. Na základě výše uvedených údajů se jeví interakce ABAD-Aß jako perspektivní cíl pro farmakoterapeutický zásah. Bylo připraveno 20 v literatuře dosud nepopsaných molekul a 4 molekuly popsané v literatuře za jiným účelem než je inhibice ABAD. Na základě in-vitro ověření aktivity sloučenin bylo vytipováno několik vhodných molekul.

Advantages
It is known from the literature that systemic treatment using ABAD-DP (“ABAD decoy peptide” enriched in the amino acid sequence allowing passage through the membrane and enter the mitochondria) in an animal model of AD improve cognitive abilities in comparison with the untreated group.

Potential Applications
Current therapeutic options in AD are inadequate, because they only slow down the progression of dementia and improve the quality of life of patients, but do not cure the cause of their own disease. Therefore, the worldwide pressure on finding new drugs for the treatment of AD is very strong.

Download in pdf here: technology summary – ABAD ENG

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