Laron Syndrome

Patients with growth hormone receptor deficiency, or Laron syndrome, appear to have lower than average risk factors for cardiovascular disease, according to a new study. A new study highlights possible cardiovascular health advantages in individuals with a rare condition known as growth hormone receptor deficiency (GHRD), also called Laron syndrome. GHRD, which is characterized by the body's impaired ability to use its own growth hormone and results in stunted growth, has been linked in mice to a record 40% longevity extension and lower risks for various age-related diseases. However, the risk of cardiovascular disease in individuals with GHRD has remained unclear until now, leading to the speculation that in people, this mouse longevity mutation may actually increase cardiovascular disease. The study, appearing in Med on April 26, 2024, is the latest product of an international collaboration spanning nearly 20 years between Valter Longo, professor of gerontology at the USC Leonard Davis School of Gerontology, and endocrinologist Jaime Guevara-Aguirre of the Universidad San Francisco de Quito, Ecuador. Over the past two decades, Longo, Guevara-Aguirre and colleagues have examined the health and aging of people with the gene mutation that causes GHRD. This rare mutation -- found in just 400 to 500 people worldwide -- was identified in a group of Ecuadorians whose ancestors had fled Spain during the Inquisition more than three centuries ago. The mutation leaves them with ineffective growth hormone receptors and results in a type of dwarfism. The team's previous research has indicated that while GHRD/Laron syndrome reduces growth, it also appears to reduce the risk of several age-related diseases. Although the Ecuadorians with GHRD have a higher rate of obesity, they have a very low risk of cancer and Type 2 diabetes. They also appear to have healthier brains and better performance on tests of cognition and memory. For the current study, the research team examined cardiovascular function, damage, and risk factors in GHRD subjects and their relatives. Researchers conducted two phases of measurements in Los Angeles and Ecuador, involving a total of 51 individuals, with 24 diagnosed with GHRD and 27 relatives without GHRD serving as controls. Key findings from the study included: "These findings suggest that individuals with GHRD have normal or improved levels of cardiovascular disease risk factors compared to their relatives," said Longo, senior author of the new study. "Although the population tested is small, together with studies in mice and other organisms this human data provide valuable insights into the health effects of growth hormone receptor deficiency and suggest that drugs or dietary interventions that cause similar effects could reduce disease incidence and possibly extend longevity." Along with co-corresponding authors Longo and Guevara-Aguirre, the study's coauthors included Amrendra Mishra and Priya Balasubramanian of USC; Carolina Guevara, Álvaro Villacres, Gabriela Peña, and Daniela Lescano of the Universidad San Francisco de Quito; Alexandra Guevara of the Instituto de Endocrinologia Metabolismo y Reproducción (IEMYR) in Quito; Marco Canepa of the University of Genova, Italy; and John Kopchick of Ohio University. Funding including National Institutes of Health/National Institute on Aging grant P01 AG034906 to Longo.

September 09, 2019 09:00 ET | Source: Generex Biotechnology Corporation * Patented cell encapsulation technology enables cell implantation for therapeutic and regenerative medicine application without immune system rejection * Microcapsules formulated with ultra-purified alginates and poly-L-ornithine previously have previously received authorization from the EMEA and Italian Medicines Agency for for use in patients with type 1 diabetes (T1D) * 4 transplanted human patients with long-standing T1D have shown evidence of grafted encapsulated islet cell function throughout 5 years of post-transplant follow-up * Altsulin® (Microencapsulated Sertoli Cells) currently in human proof-of-concept clinical study in patients with Laron syndrome * Clinical development of Altsulin for the treatment of T1D MIRAMAR, Fla., Sept. 09, 2019 (GLOBE NEWSWIRE) -- Generex Biotechnology Corporation (OTCQB: GNBT) is pleased to announce that the Company has signed a binding letter of intent (LOI) to partner with ALTuCELL, a privately held biotechnology company in a stock and cash transaction. ALTuCELL, Inc. is a cellular engineering and biotech company backed by sound research and science focused on fulfilling a large "unmet need" in cell, molecular and regenerative therapy for treatment of diabetes and other autoimmune and neurodegenerative diseases. The company’s proprietary and unique technology overcomes the major barriers to transplantation by a novel strategy utilizing patented microencapsulation technology, enabling a transplantable, cell-based therapy that avoids detection and rejection by the immune system. ALTuCELL is presently engaged in a human proof of concept study designed to evaluate the ability of Altsulin to increase serum levels of Insulin-Like Growth Factor-1 (IGF1) in patients with Laron Syndrome (aka Laron-type dwarfism), an autosomal recessive disorder characterized by an insensitivity to growth hormone (GH), usually caused by a mutant growth hormone receptor. Patients with Laron Syndrome, a pediatric orphan disease, have the lowest level IGF1 values seen in any disease. Altsulin has demonstrated significant effectiveness in increasing serum levels IGF1 in all pre-clinical animal models tested to date, providing the pharmacologic basis for the implanted Sertoli Cell therapy. For additional information please visit the ALTuCELL web site. In animal models, ALTuCELL’s microencapsulated cell technology have been proven safe and effective not only in the treatment of T1D, but also of other chronic diseases, including neurodegenerative diseases such as Huntington’s disease and lethal neuromuscular disorders like Muscular Dystrophy. As for the latter, pre-clinical data look very strong toward clinical application. The ALTuCELL microencapsulation technology has also demonstrated effective implantation of numerous cell types including Mesenchymal Stem Cells extracted from the post-partum human umbilical cord (Wharton’s Jelly) for the treatment of early onset type 1 diabetes and other regenerative medicine applications. Joe Moscato, President & Chief Executive Officer of Generex stated, “We can’t be more excited about this partnership with ALTuCELL and their CEO Gary Harlem to join forces in our common goal to conquer diabetes. With this acquisition, we are reigniting our diabetes-focused development efforts, gaining a clinical-stage cellular therapeutic product, Altsulin for the potential cure of Type I diabetes, as well as the best-in-class, globally patented cellular microencapsulation technology that enables rapid, patent-protected pipeline expansion of cellular and regenerative therapy products. We are building NuGenerex Health MSO with a team of endocrinologists and primary care physicians to provide integrated specialty healthcare services for patients with diabetes. Plus, we are now positioned to bring back the Oral-Lyn program with the clinical development of our reformulated Oral-Lyn II that is designed to require only two sprays for glycemic control. Generex will once again be a force in diabetes, and we are happy to have ALTuCELL as an integral part of our plans.” Gary Harlem, ALTuCELL’s President & Chief Executive Officer commented, “I have made it my life’s mission to find a cure for Type I Diabetes, and have been working for nearly a decade with Dr. Riccardo Calafiore, Dr. Giovanni Luca and Dr. Giuseppe Basta from the University of Perugia Department of Medicine to perfect the technology for cellular implantation. Our patented process ensures that our microcapsules are pure and virtually endotoxin free and maintain their immunoisolatory properties in vivo, with no toxicities nor immune rejection. We are excited to begin U.S. trials over the next few months, working closely with our expert scientific team and founders. Mr. Harlem continued, “We are extremely happy to join Generex and to work with their highly experienced management team to bring Altsulin through clinical development to the market. It is great to have a diabetes expert like Dr. James 'Andy' Anderson on the Generex team for guidance on our development program. Additionally, the NuGenerex MSO model provides a number of benefits to us, including access to physician researchers and a large population of patients with diabetes who will be eligible for clinical trials. With the Generex end-to-end model, these doctors and patients are not only research partners but also future customers. We are excited for the future.” Generex will provide additional details on the deal as the transaction is finalized.