Image: An innovative ELISA kit can identify diabetes patients at higher risk of developing lethal cardiovascular disease or renal failure (Photo courtesy of MyGenetx).
A breakthrough ELISA kit, based on the Haptoglobin 2-2 (Hp 2-2) protein marker, can identify diabetes patients at higher risk of developing lethal cardiovascular disease or renal failure, thereby enabling them to take Vitamin E, a nutritional supplement shown to be of great benefit to them but posing harm to the remaining non-HP 2-2 diabetic population. An application for the CE mark for the test is currently in progress, with FDA certification planned for the US market.
Haptoglobin (Hp) is a plasma protein that every person carries in one of three variants: Hp 1-1, 2-1, or 2-2. With heart disease as the leading cause of death among diabetics, it has been shown that diabetes patients with the Hp 2-2 type, representing around one-third of all diabetics, face a much higher risk of heart disease compared to the remaining two-thirds of diabetics that have other Hp types. Conversely, studies have also shown that Vitamin E supplementation reduces heart attacks and death from cardiovascular disease by 50% in diabetes patients with HP 2-2, while having harmful effects on those with other Hp types.
Now a novel test developed by BioRap Technologies (Haifa, Israel) brings a much-needed solution to this dilemma. By differentiating diabetes patients with the Hp 2-2 type from the general diabetic population, the new test allows them to receive the Vitamin E treatment, while excluding diabetics with other Hp types. The Hp test can indicate to the physician which of the three Hp types the patient belongs to, thus determining the risk of developing cardiovascular and renal diseases, and allowing for the application of appropriate treatment. BioRap's Hp typing test has been validated for 99% accuracy by eight different clinical studies, and is easily and rapidly performed from 20 µl of serum or plasma using the ELISA based kit.
BioRap's research team is headed by Prof. Andrew P. Levy, MD, PhD, FACC, whose record includes cutting-edge investigation for some 13 years in Haptoglobin Genomics and Therapeutics, and 25 years in Molecular Cardiology. Prof. Levy and other researchers have confirmed in 11 studies in the US, Europe, and Israel that diabetics (of both type I and II) carrying the Hp 2-2 genotype have up to a five-fold increased risk of developing cardiovascular disease and end-stage renal disease as compared to diabetics carrying the Hp 2-1 or Hp 1-1 genotypes.
Nevertheless, Hp typing and Vitamin E treatment of Hp 2-2 diabetics still remain not included in standard clinical guidelines on diabetes treatment. This could change if a major clinical trial replicates, on a wider scale, the findings of the two existing smaller-scale trials. If such a trial were to be carried out by a pharmaceutical company, its costs could exceed USD 40 million. However, since Vitamin E is not patentable medicine, no company or private investor would profit sufficiently to justify funding such a clinical trial. As to public health agencies such as NIH or EU, they do not have this level of funding available in the current environment.
As a solution, Dr. Irit Hochberg with the Institute of Endocrinology, Diabetes & Metabolism at Rambam Health Care Center (Haifa, Israel), who was involved in the first diabetes Hp studies, is calling for HD-VERDICT, a pragmatic trial in which 6,000 diabetics with Hp 2-2 will be randomly assigned to Vitamin E at 400 IU/day or a placebo, and followed for heart events and deaths. According to Dr. Hochberg, "by way of existing infrastructure and avoiding heavy staff expenses of a clinical research organization, such a trial is expected to cost no more than USD 1 million."
Dr. Hochberg added that, "over 150 million people in the world have both diabetes and Hp 2-2. Should the proposed study confirm results of the previous small-scale studies, the public health benefits would be enormous, justifying mass-scale Hp typing and Vitamin E treatment. Simulation of the previous results over 50 years at the Kaiser Permanente Healthcare System (Oakland, CA, USA) demonstrated that such treatment would increase the diabetics' life expectancy by 2.5 years, compared with an increase of only 0.9 years due to prevailing lipid-lowering therapy."
According to Dr. Orit Shaked, chief executive officer of BioRap Technologies, "every year, diabetes causes 1.5 million deaths and costs USD 825 billion in worldwide healthcare spending. For every 1,000 diabetics of the Hp 2-2 type, treatment with vitamin E could prevent 75 myocardial infarction admissions, 31 cardiac surgical procedures, plus 19 percutaneous coronary interventions. As a result of the new test gaining worldwide application, an extensive diagnostic and therapeutic potential could be unleashed, addressing the needs of a diabetic population of over 420 million worldwide -- and growing by 10 million per year -- of which 30 million are in the US."
BioRap's Haptoglobin ELISA kit and indications for its use are covered by a wide portfolio of approved and pending patents. License for European distribution has been granted and the test is currently in the CE approval process. BioRap is currently in the process of exploring a suitable licensing agreement covering the US market. The potential US licensee is envisaged as a nationwide distributor, or a manufacturer with similar distribution capabilities.
BioRap Technologies Ltd. is a technology transfer company built upon innovations and patented technologies developed by research scientists at the Rappaport Family Institute for Research in the Biomedical Sciences, affiliated with Technion Israel Institute of Technology (Haifa, Israel). The company's approach, which identifies commercial opportunities emanating from scientific research and advanced technologies, has among others resulted in the development of Azilect (Rasagiline), a successful drug in the treatment of Parkinson's Disease, currently marketed worldwide by Teva Pharmaceuticals. BioRap offers a one-stop shop to advance the research and development of significant discoveries by fostering strategic collaborations with industry, through licensing, sponsored research, or new ventures.
Rambam Health Care Center
Kaiser Permanente Healthcare System
Technion Israel Institute of Technology