Alzheimer disease (AD) is a progressive neurodegenerative disorder in which age is the most important risk factor. Victims lose their memories, personalities, sense of time, identity, and eventually their lives. The disease afflicts around 5.4 million people in the U.S., where the memory-robbing illness is the 6th-leading killer of Americans, according to Alzheimer’s Association. The association estimates that more than $200 billion will be spent between drug makers and patients for research, medication and caregivers this year. AD brain is characterized by both extracellular (amyloid plaques) and intracellular aggregates (neurofibrillary tangles). Amyloid aggregates, formed by the amyloid-β-peptide (Aβ), the putative trigger of the pathological events observed in the disease. Other events include oxidative stress and inflammatory reactions. There is currently no treatment to revert the disease.

Research is at a critical point, particularly as investigators question whether knocking down level of amyloid in patients with an established case of the disease can do any good, therefore, there is a new focus on alternative pathways, including alterations in intracellular signaling with emphasis on prevention techniques and cognitive improvements.

IB-AD: is a product that showed anti-Alzheimer's potential as it is neurogenesis. IB-AD works on both canonical and non-canonical WNT pathways. Clinical trials have demonstrated reduction in inflammation in the brain and prevention of cognitive impairment. IB-AD activates WNT pathway, activates Peroxisome Proliferators, reduces Tau hyperphosphorylation, and stimulates LTP.

Target Indication:
Alzheimer Disease and related cognitive impairments

Route of Administration:
Oral

Mechanism of Action:

• Activates Wnt signaling
• Inhibits GSK-3β
• Reduces tau hyperphosphorylation
• Activates Peroxisome Proliferators
• Induces postsynaptic proteins and synaptic function (LTP)
• Stimulates neurogenesis

Pre-clinical Result:

• IB-AD prevents inflammatory and oxidative damage triggered by the high Aβ deposits
• IB-AD acts on brain neuropathology, learning and memory
• IB-AD alleviates memory decline induced by Aβ deposits by inducing postsynaptic proteins.
• IB-AD activates Wnt pathway and reduces tau phosphorylation.
• IB-AD increases postsynaptic potentials in hippocampal CA1 slices, and prevents Aβ oligomer effects
• IB-AD protects from astrocytic proliferation and protein nitrotyrosination induced by Aβ in a transgenic AD model.
• IB-AD prevents the decrease of synaptic proteins triggered by Aβ oligomers
• IB-AD inhibits GSK-3β, and therefore decreases long-term depression (LTD).

Key Patents and IP Rights

1. US Patent Number: 8,084,495: Composition of labdane diterpenes extracted from andrographis paniculata, useful for the treatment of autoimmune diseases, and alzheimer disease by activation for PPR-gamma receptors
2. US Patent awarded April 2015, Patent to be published in June 2015: PCT Serial No. US61/814,445: Andrographolide stimulates neurogenesis and is useful for the treatment of cognitive impairment including Alzheimer, Dementia, Parkinson Disease, autism, schizophrenia by activation of the WNT and GSK3 pathways.

Publications:

1. Biochem. J. (2015) 466, 415–430: Andrographolide activates the canonical Wnt signalling pathway by a mechanism that implicates the non-ATP competitive inhibition of GSK-3β: autoregulation of GSK-3β in vivo
2. Molecular Neurodegeneration (2014), 9:61: RESEARCH ARTICLE Open Access Andrographolide reduces cognitive impairment in young and mature AβPPswe/PS-1 mice