Alzheimer's Disease
Alzheimer’s Disease (AD) is a progressive brain disease that slowly destroys memory and thinking skills. It is the most common cause of dementia among older people, with symptoms often appearing by the age of 60. The effects are loss of cognitive function such as thinking, remembering and reasoning to the extent of interfering with a person’s daily life.
- Amyloid plaques deposited in the brain are believed to precede the onset of dementia by many years. These plaques are seeded by the “bad amyloid” (Αβ42), and cause or contribute to the cognitive decline of AD patients.
- Alzheimer’s Disease afflicts more than 5.3 million Americans (33 million worldwide) at an annual cost of 200 billion dollars.
- New cases of Alzheimer’s Disease are on the rise, and it is projected that by 2020 nearly 6 million people in the US will be initially diagnosed with Alzheimer’s dementia.
- Early preventative treatment is dependent on the diagnosis of amyloid plaque pathology before dementia.
- Amyloid plaques are best detected by radiolabeled PET scans and may be prevented and removed by the right medicine.
Our Technology
Our patented technology of Gamma-Secretase Modulators (GSMs) is based on an innovative modulation of a key enzyme in the amyloid pathway, called γ-secretase. Our approach alters the production of amyloid proteins by decreasing the toxic form found in AD brains (Αβ42) but increasing the non-toxic forms (Αβ37 and Αβ38) which help reduce plaque deposition.
The GSM approach avoids inhibition of other γ-secretase targets potentially minimizing adverse side-effects. Therapies based on these compounds may be used to treat a broad range of amyloid-based diseases including cerebral vascular dementia, inclusion body myositis, Alzheimer’s dementia associated with Down’s Syndrome patients, and more.
Our Product
NGP has selected a clinical candidate, NGP 555, which is a small molecule modulator of the gamma-secretase complex. NGP 555 is a potent molecule, which crosses the blood-brain barrier and is effective in lowering the brain biomarkers Αβ42 and Αβ40 while showing an increase in the Αβ38 and 37 peptides with no effect on Notch processing. Key “proof of concept” studies with NGP 555 showed significant reduction of amyloid plaques in the brains of mice harboring the human amyloid precursor protein, reduction of cognitive impairment, and removal of amyloid plaque from synapses with increase in synaptic function. Phase 1 clinical trials have shown dose-related blood and brain levels of NGP 555 after oral dosing, good reduction of Ab42 and increase of Ab37 and 38, and good safety with no side effects at highest doses after 14 days of oral dosing.
NGP 555 represents a unique opportunity to clinically translate these biomarker findings to the reduction of amyloid pathology, culminating in the prevention of cognitive decline in Alzheimer’s Disease.
Patents
Mechanism of action, method of treatment, and solid dosage form formulations for oral dosing.
U.S.Patent 7,244,739 plus EPO, India, China, Canada, Mexico and other territories
U.S.Patent 7,781,442
U.S.Patent 7,799,808
U.S.Patent 8,017,629
Publications
Kounnas, MZ, Lane-Donovan, C, Nowakowski, DW, Herz J, Comer WT: “
NGP 555, a gamma-Secretase Modulator, Lowers the Amyloid Biomarker, Abeta42, in Cerebrospinal Fluid while Preventing Alzheimer’s Disease Amyloid Pathology and Cognitive Decline in Rodents”Alzheimer’s and Dementia: TCRI, December, 2016.
Maria Z. Kounnas et. al.
Neuron 67, 769-780, September 9, 2010.
“
2-Aminothiazoles Derivatives as Potent Gamma-Secretase Modulators for the Prevention of Alzheimer’s Disease”: Soan Cheng, Ph.D., American Chemical Society, 2010
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Gamma-Secretase Modulators for the Prevention of Alzheimer’s Disease”: Maria Z. Kounnas, Ph.D., Society for Neurosciences, Nov., 2011
