Adipotide/ FTPP 2MG*50vials

Product History

Adipotide was first synthesized by Dr.Wadih Arap and Renata Pasqualini in their efforts to develop a drug with therapeutic properties in the treatment of cancer. The researchers specifically designed this peptide such that it would target and prevent the supply of blood to cancer cells hence inhibiting their growth. Study results however indicated that Adipotide starves fat cells from the supply of blood and as such leads to their death and reabsorption into the body. Despite the high success rate noted in the initial studies performed in rats and monkeys, there were minor negative side effects that were observed, such as small kidney lesions (with potential to cause kidney failure if not treated) and dehydration. With proper medication, these adverse effects are preventable.

In 2012, Arrowhead Research Corporation, a U.S. based therapeutic company that has programs for development in obesity, oncology, and infectious disease was given the go ahead by FDA (U.S. Food and Drug Administration) to begin the Phase I Clinical Trial which seeks to evaluate the safety profile of the peptide in obese prostate cancer patients. It was the company’s inaugural obesity drug candidate and the Phase I clinical trial was performed by MD Anderson Cancer Center (University of Texas). The human trials were commenced two months following the report released by the company indicating positive results obtained in terms of weight loss when Adipotide was administered to obese rhesus monkeys. The company had received results from various animal based experiments that indicated potential therapeutic significance of Adipotide in the treatment of Type II diabetes. Adipotide is licensed to The University of Texas’ MD Anderson Cancer Center and The University has licensed Ablaris Therapeutics, a pharmaceutical company to carry our further research on the drug.

Scientific Study

Following multiple animal based experimental studies which have shown that Adipotide leads to significant weight loss, rapid metabolic changes, and decreased food intake which affect type II diabetes. Arrowhead Research Corporation (ARWR), a therapeutic company, began phase I clinical trials to test Adipotide as a therapeutic drug for obesity. The clinical trial sought to study a single 28 day cycle of the peptide among patients suffering from castrate resistant prostate cancer and who were not under any standard treatment options. The primary aim of the study was to establish the maximum tolerable dose, measure weight changes, evaluate pharmacokinetics, and monitor the progress of the disease. There were also additional secondary outcome measures. Adipose (fat) tissue is known to generate substances that are likely to cause prostate cancer growth. The clinical study is being carried out by scientists at MD Anderson Cancer Center (University of Texas). The scientists are also seeking to establish whether decreases in white fat which is linked with obesity treatment can generate substantial weight loss, a drop in food intake, and quick metabolic changes with effects on Type II diabetes in a number of experimental animal models.

In the above clinical trial, the researchers are trying to establish the highest tolerable dose of Prohibitin-TP01 (adipotide) that can be administered to advanced prostate cancer patients. The study will only feature patients who have carcinoma of the prostate which is advanced/metastatic (incurable) and who are obese (BMI >30 kg/m2). However, none of the considerable subject should have small cell carcinoma. This study has an estimate of 39 study subjects and it commenced in May 2012 with the estimated completion date I terms of data gathering being in May 2017. The patients will be subcutaneously administered with Adipotide on a daily basis for a period of 28 days. The study involved five dose levels whereby three patients were tested in each dose level. The starting dose for the therapy is 0.03 mg/kg which is to be administered through injections under the skin with a single daily over the 28 days of each cycle. The groups are to be administered with increasing dose levels but with reference to evaluation of observed safety of the previous dose level. The doses will be administered until the researchers arrive at the highest Adipotide dose that has acceptable safety profile or after all the five dose levels have been completed.

Various independent studied performed with Adipotide have shown that treatment with Adipotide brings about a body weight loss of approximately 30 percent within 28 after commencement of the treatment, on the other hand, lean rodents do not exhibit any weight loss. Based on scientific studies, it has been established that obese animals experience rapid enhancement in pro-diabetic metabolic markers, such as enhanced glucose tolerance, enhanced insulin sensitivity, and a decline in serum triglycerides with subjects receiving Adipotide treatment for about 2-3 days.

In studies that used non-human primates), researchers investigated Adipotide effects when administered to obese old world monkeys. When the monkeys were treated with Adipotide, they underwent targeted adoptosis in the white blood vessels within the white adipose tissue. This brought about rapid weight loss and significant enhancements in their resistance to insulin. The researchers utilized dual-energy x-ray absorptionmetry as well as magnetic resonance imaging to substantiate marked decrease in white fat tissue. When optimal doses (experimentally determined) were administered to three monkeys from various species, the researchers observed predictable and reversible alterations in the monkeys’ renal proximal tubule function. Based on results from this study, researchers concluded that Adipotide has a potential to be developed into a therapeutic drug to assist fight obesity in humans.

In another monkey based study, researchers evaluated Adipotide in obese rhesus monkeys. Rhesus monkeys are commonly used in research due to the high number of obese monkeys as a result of their eating patterns and their lazy nature. The researchers observed that after 28 days of Adipotide treatment and another 28 days of recovery in rhesus monkeys that were obese, the primates lost 11% (on average) of their body weight. The researchers also observed a decline in body mass index and a reduction in abdominal circumference and an indication of marked enhancements in insulin resistance (which is a marker for type II diabetes). The drug was administered by means of injections with the dosage being based on the weight of the specific monkey. The lean monkeys did not exhibit any effects following administration of the experimental drug. The monkeys featured in this study exhibited acceptable tolerance although they experienced a drop in their kidney function while they were undergoing the treatment. However, this did not pose a major risk as it normalized once the treatment was terminated. On the other hand, the researchers noted that once the treatment was terminated, the rhesus monkeys began regaining weight.

Molecular studies demonstrated that Adipotide has a specific stereo-chemical (3D) conformation that makes it bind with two receptors within the body which are prohibitin and ANXA-2. The two receptors are usually found on the surface of the inner most wall lining in the blood vessels that support white adipocytes. The peptide has been shown to kill fat cells in a programmed manner whereby it selectively deprives fat cells of nutrients. These fat cells then die as a result of starvation and then bring about the release of cascases (enzymes which instigate programmed cell death). This is achieved through the peptide’s action on specific two receptors (ANXA-2 and prohibitin) which are found on the endothelial wall of the vessels that supply blood to white adipocytes. Abdominal obesity is highly linked to white adipocytes.

In studies performed by Mikhail G Kolonin and colleagues, it was observed that Adipotide when administered to mice stimulated apoptosis in the vascular bed of their white adipocytes. As a result, the mice were able to attain normal metabolic processes. In another similar study, Kirstin F. Barnhart and colleagues’ demonstrated that Adipotide initiated adoptosis in the vascular bed of the monkeys’ white adipocytes and this brought about weight loss and a restoration of normal insulin function. Based on the results from these studies, Adipotide causes weight loss by initiating selective adoptosis.