Pharma Focus Asia

ModGene Pharma Announces Issuance of US Patent for Alzheimer's Disease Prevention

Thursday, July 20, 2017

ModGene Pharma, LLC today announced the issuance of US Patent 9,707,231, entitled "Compositions and Methods for Reduction of Amyloid-beta Load." The claims cover the use of an imatinib-related compound for reduction of amyloid-β production in Alzheimer's disease. The compound, imatinib para-diaminomethylbenzene trihydrochloride, is three-fold more potent in inhibiting amyloid-β production than imatinib and exhibits only 1/16th of the activity of imatinib in the inhibition of Abl kinase (the imatinib target in leukemia), resulting in a selectivity ratio of nearly 60 for the Alzheimer's indication.

"This patent allowance is a very significant milestone as it supports our unique approach to Alzheimer's disease prevention and expands our intellectual property portfolio.  We are the first to have identified a 'statin'-type approach to Alzheimer's prevention that utilizes compounds that can be investigated in clinical trials relatively soon," said Greg Sutcliffe, CSO and CEO of ModGene Pharma.

ModGene Pharma's patent portfolio includes recently issued patents in Europe and other countries that cover the dual discoveries that pathogenic amyloid-β has a primary source in peripheral tissues outside of the brain (particularly the liver) and that the FDA-approved anti-leukemia drug imatinib is effective in reducing amyloid accumulation in the brain, even though it does not cross the blood-brain barrier.

In mouse studies seeking to identify Alzheimer's disease modifier genes, ModGene demonstrated that the level of expression of the Presenilin2 gene by the liver regulates the accumulation of pathogenic concentrations of Alzheimer's disease-initiating amyloid-β within the brain. The anti-leukemia therapeutic imatinib (trade name Gleevec), which does not cross the blood-brain barrier, reduced liver production of amyloid-β and lowered its accumulation in the brain below pathogenic levels. The peripheral amyloid-β origin concept has been confirmed in mouse studies which show that hippocampal amyloid-β accumulation accompanied by cognitive deficits initiated by endotoxin-induced peripheral inflammation is eliminated by imatinib administration as is tau hyperphosphorylation, and that imatinib administration to amyloid plaque-bearing APP transgenic mice led to plaque reduction and cognitive improvement.

In humans, longitudinal studies have shown unequivocally that plasma amyloid-β levels are consistently higher in individuals destined to develop Alzheimer's as compared to healthy controls both in autosomal dominant carriers (mutations found in APP, PSEN1 and PSEN2 genes) and in Down syndrome patients. The elevation of plasma amyloid-β (specifically Aβ-42) in mutation carriers was shown to be stable for decades preceding age of onset, suggesting a prolonged period of progressive accumulation that can be halted by drugs lowering its production in the periphery.

"These studies suggest that prophylactic reduction of amyloid-β at the site of its production in the livers of aging humans before plaque deposition begins has the potential to lower the incidence of Alzheimer's and point to the identities of drugs that can accomplish that goal. The Company is continuing to explore business opportunities and is seeking investors and pharmaceutical partners to run clinical trials that would allow development of Alzheimer's disease-preventing medications," said Dr. Sutcliffe.

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