Platform 2018-01-07T02:16:36+00:00
 
 

Inflammation & Tissue Damage

A Root of Major Contributing Factor in Many Disease & Conditions

Inflammation with resultant tissue damage contributes to the pathogenesis of a broad range of human diseases, and plays a significant role in human aging, with increased risk for disease, poor physical functioning and mortality. Araim discovered, characterized, and named the receptor that is a master regulator in the cascade of damage, the innate repair receptor that activates tissue protective, reparative and anti-inflammatory signaling pathways to address the inflammation and tissue damage associated with diseases

Araim Pharmaceuticals lead compound, Cibinetide, is in clinical development addressing unmet needs in neuroscience and diabetes complications. We have developed an extensive peptide library of IRR activators, with in-vivo proof of concept efficacy for 10 unique compounds and an extensive catalogue of scientific literature in collaboration with leading academic researchers around the globe.

Atherosclerosis (hardening of the arteries) is a process driven to a significant extent by inflammation of the inner wall of arteries which leads to the formation of plaque. High levels of lipids (cholesterol and triglycerides) in the blood stream contribute to this inflammation. The Watanabe rabbit has a genetic mutation that increases circulating lipids. Buy eight months of age this rabbit develops severe atherosclerosis of the coronary arteries, as shown in the top image (Control) with critical blockage of the artery and with inflammation localized within the plaque (the brown staining above the label “atheroma”). Treatment with cibinetide three times per week significantly reduced both plaque size and the extent of local inflammation (bottom image).

Traumatic brain injury (TBI) is a common, devastating condition which currently lacks an effective treatment. A significant blow to the head activates inflammation which the brain tissue causing the accumulation of fluid (edema) and increased pressure within the brain due to confinement by the skull, which worsens the injury, and as a result, brain tissue dies, leading to neurological and cognitive deficits. One useful animal model of TBI Is delivery of all calibrated blow to the surface of the brain of a rat and evaluating the following loss of brain tissue and deterioration of memory. In this example, a rat was subjected to TBI under anesthesia, resulting in the loss of a large amount of brain tissue when examined 15 days later (Top; Control). In contrast, treatment with cibinetide following the TBI protected brain cells from injury resulting in a preservation of brain tissue (Bottom) as well as of cognition as evaluated by testing memory

Many disease processes result in nerve damage (neuropathy), leading to impaired of sensation, movement, or bodily function, depending upon the specific nerves involved. As only two examples, the current global epidemic of diabetes is a major cause of debilitating neuropathy, as is sciatic nerve injury (sciatica) caused by slipped discs. A useful animal model of neuropathy involves cutting the sciatic nerve in a rodent. This injury to the nerve activates inflammatory processes which includes the accumulation of specific immune cells (microglia) within the sciatic nerve regions within spinal cord (bright areas in the top image), which leads to development of severe neuropathic pain. Treatment with cibinetide after the sciatic nerve injury prevents the immune cell accumulatio and the resulting pain (lower image).

The kidney is a very active organ which depends upon a well-maintained blood flow to function properly. If blood flow is disrupted (ischemia), and the restored (reperfusion), and intense inflammatory reaction results. This, in turn, causes the swelling and death of kidney cells, especially within the specialized cell of the kidney tubules. As an example, the blood flow to a pig’s kidney was cut off for 45 minutes and then restored. As a consequence, tubular cells became pale and swollen, a classical indication of injury (top image; control). In contrast, treatment with cibinetide immediately following the restoration of blood flow noticeably reduced inflammation and kidney cell loss (bottom image), resulting in preserved kidney function. Additionally, cibinetide significantly reduced scarring in the kidney following injury, a major cause of progressive kidney damage caused by numerous different types of injury.

Improperly treated diabetes leads to progressive, irreversible damage of multiple tissues and organs, including the eye (retinopathy), as a result of inflammation and injury to the cells. For example, rats with 6 months of untreated diabetes had markedly elevated levels of inflammatory markers and dying nerve cells within the retina of the eye, as indicated by the bright dots in the top image (control). In contrast, daily cibinetide treatment reduced inflammation and largely prevented the loss of these cells (lower image).

Tissue injury sets in motion several of the body’s repair pathways to act together for healing nan regeneration. Cibinetide has been shown to improve would healing under a variety of conditions, including diabetes, by decreasing tissue injury, controlling inflammation, and promoting the formation of new blood vessels which are essential for healing to occur. One common would type which tends to heal very poorly is bed sores. In a rat model of bed sores, pressure was applied intermittently to the skin in a pattern mimicking that of a bed-ridden patient. Subsequently, skin breakdown occurred, followed by activation of healing, a process in which the surrounding normal skin grows into the damaged area (darker regions in the images) to eventually close the wound. Cibinetide treatment after wounding, significantly accelerated the healing process, as illustrated in the bottom image.

The liver is often the target of damage arising from a wide variety of disease processes or from toxins. Currently, obesity and diabetes are a widespread cause of significant progressive liver damage, including scarring, ultimately leading to an increased risk of liver cancer. Specifically, obesity decreases the beneficial effects of insulin on cell functions (insulin resistance) which leads to high blood lipid levels (cholesterol and triglycerides) and deposits in the liver (fatty liver). This process causes liver inflammation which can then lead to progressive liver disease. Similar to the humans, rodents offered a high calorie, palatable diet (high fat and sugar) become obese, develop insulin resistance, and deposit excess lipids in the liver (arrows; red stained areas in the top image). Daily cibinetide treatment resulted in a dramatic reduction in insulin resistance, resulting in a reduce storage of lipids within the liver (bottom image).

Araim Scientific Platform has been investigated in collaboration with an extensive network of leading global academic research scientist

Sarcoidosis Daniel Culver Cleveland Clinic
Diabetic Neuropathy Robert Schmidt Washington University School of Medicine
Diabetic Retinopathy Alan Stitt Queen’s University, Belfast
Neuropathy Rayaz Malik Weill Cornell Medicine-Qatar
Pain & Neuropathy Albert Dahan Leiden University Medical Center
Diabetes Claes-Göran Östenson Karolinska Institute
Pain Biomarkers Torsten Gordh Uppsala University
Heart Disease Masanobu Kawakami Jichi Medical University
Aging Edward Lakatta National Institute on Aging
Kidney Injury Christoph Theimermann William Harvey Research Institute
Burn Injury Martin Yarmush Harvard Medical School
Alzheimer’s Disease Michael Bacher University of Marburg
Islet Transplantation Torbjörn Lundgren Karolinska Institute
Traumatic Brain Injury Claudia Robertson Baylor College of Medicine
Epilepsy Nihal de Lanerolle Yale University School of Medicine
Inflammatory Bowel Disease Gunther Weiss Medical University of Innsbruck

Extensive research has resulted in >70 peer-reviewed scientific publications.