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Alzhieime's Disease

Alzheimer’s disease is the sixth-leading cause of death in the United States. An estimated 5.3 million Americans of all ages had Alzheimer’s disease in 2015. The numbers are projected to double by 2050. The cost in 2015 for all individuals with Alzheimer’s disease and other dementias is estimated at $226 billion.

Targeting amyloid in patients with Alzheimer’s disease may not be enough to stop the progression of the disease. We urgently need to identify drug targets that not only slow the progression but, more importantly, repair the damaged brain in Alzheimer’s disease.

The research is now being directed towards the repair mechanism and the biochemical cascades that promote cell survival and regeneration. The generation of new neurons requires adequate blood supply to meet the energy and nutritional demand, thus the process of neurogenesis and angiogenesis are linked together and are coordinated.

We demonstrated that stimulation of endothelin B receptors using PMZ-1620 produced a marked recovery. In Alzheimer’s disease animal model, we validated that PMZ-1620 significantly improved learning and memory deficit, decreased oxidative stress, and enhanced angiogenesis as well as neurogenesis.

A significant improvement in learning and memory deficit was also found in APP/PS1 [Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas] transgenic mice which overexpress both mutant human APP(695) with the Swedish (K670N, M671L), Florida (I716V), and London (V717I) FAD mutations and human PS1 harboring two FAD mutations, M146L and L286V.

Status of Alzheimer's Disease

Product
Pre-Clinical
Clinical

phase 1

phase 2

phase 3

market

Alzheimer's Disease (PMZ-1620)

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Publications

  • Briyal, S., Nguyen, C., Leonard, M., and Gulati, A. (2015) Stimulation of endothelin B receptors by IRL-1620 decreases the progression of Alzheimer's disease. Neuroscience 301, 1-11
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  • Oesterling, B. M., Gulati, A., and Joshi, M. D. (2014) Nanocarrier-based approaches for treatment and detection of Alzheimer's disease. J Nanosci Nanotechnol 14, 137-156
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  • Briyal, S., Shepard, C., and Gulati, A. (2014) Endothelin receptor type B agonist, IRL-1620, prevents beta amyloid (Aβ) induced oxidative stress and cognitive impairment in normal and diabetic rats. Pharmacol Biochem Behav 120, 65-72
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  • Briyal, S., Philip, T., and Gulati, A. (2011) Endothelin-A receptor antagonists prevent amyloid-beta-induced increase in ETA receptor expression, oxidative stress, and cognitive impairment. J Alzheimers Dis 23, 491-503
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