Thiamine Deficiency

NIH-funded trial will evaluate the effects of a synthetic version of vitamin B1 on cognitive function that was developed by Burke Institute for people with early Alzheimer's disease For more information about the trial and to find a study site, visit benfoteam.org WHITE PLAINS, N.Y., Sept. 23, 2024 /PRNewswire/ -- A completely different approach to stopping the progression of Alzheimer's disease pioneered by a research institute based in Westchester County, NY is now being tested nationwide. The Burke Neurological Institute (BNI), an affiliation of Weill Cornell Medicine, in partnership with the Alzheimer's Disease Cooperative Study (ADCS) at University of California San Diego and Columbia University Irving Medical Center, have launched a national clinical trial to investigate the therapeutic potential of a BNI and Weill Cornell Medicine-developed form of benfotiamine, a synthetic version of vitamin B1 (thiamine), as a treatment for mild cognitive impairment (MCI) and early Alzheimer's disease (AD). The BenfoTeam trial (The Phase 2A-2B study) taking place at 50 sites across the U.S. will evaluate the effects of benfotiamine on cognitive function and whether high doses benefit people 50-89 with mild AD and MCI. The trial is funded by the National Institute on Aging (NIA), a part of the National Institutes of Health (NIH). Benfotiamine is a synthetic drug which can increase blood thiamine up to 100 times the normal level. These levels of blood thiamine cannot be achieved by taking thiamine alone. The brain tissue in people with AD shows a thiamine deficiency, even with a sufficient supply of thiamine in a person's blood. The trial is investigating whether the delivery of thiamine via drug will increase the amount of thiamine getting to the brain and slow cognitive decline in people with early AD. Currently, 5.8 million Americans are living with AD with this number projected to rise to nearly 14 million people by 2050. "The approach of using benfotiamine in patients with mild Alzheimer's is very promising," said Rajiv Ratan, M.D., Ph.D., Executive Director at Burke Neurological Institute. "This clinical trial builds on years of hard work to address a disease that affects millions of patients " Howard Feldman, Director of the ADCS at UC San Diego said, "The launch of the BenfoTeam clinical trial represents a fresh approach with a potential treatment that is readily accessible, scientifically compelling, and cost-effective – that's a trifecta for a potential AD therapy in a Phase 2 trial – and benfotiamine has a strong safety profile." Gary E. Gibson, Ph.D., Professor of Neurosciences at BNI, has spent decades conducting studies to better understand Alzheimer's disease and how to develop new therapies to treat the disease. The BenfoTeam study builds on Gibson's scientific research conducted at Burke Neurological Institute – the only research institute in the U.S. dedicated to finding treatments to repair the brain and spinal cord. Gibson said many existing treatments or drugs in development only treat the symptoms of Alzheimer's disease such as amyloid plaques, but do not address the root cause of the disease. Benfotiamine has been shown to improve memory and diminish plaques, tangles, inflammation, and oxidative stress in animal models. In addition, unlike many of the other recently approved treatments for Alzheimer's disease, benfotiamine can be taken by mouth and does not require infusions. "In people with Alzheimer's disease, reductions in brain glucose utilization track closely with cognitive decline and we already know that thiamine deficiencies can cause dementia," said Gibson, who is also a Professor of Neuroscience in the Feil Family Brain and Mind Research Institute at Weill Cornell Medicine. "We think people with mild cognitive impairment and Alzheimer's disease may not be getting enough thiamine delivered to the brain." Jose Luchsinger, M.D., MPH, Vice-Chair for Clinical and Epidemiologic Research at Columbia University and a BenfoTeam trial co-Principal Investigator said, "While Alzheimer's disease impacts all aging populations, it is not clear that recently approved Alzheimer's therapies benefit underrepresented racial and ethnic groups. The BenfoTeam trial is designed for all patient populations.'' Participation in the trial for each patient will last 18 months (plus screening) and enrollment is planned for 406 participants. For more information about the trial and to find a study site, visit benfoteam.org or call 877-807-1290 (toll free). This research will be supported by the NIH's National Institute on Aging (R01AG076634). This content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH's National Institute on Aging. The ClinicalTrials.gov ID number for this study is: NCT06223360. About the BenfoTeam Partnership The BenfoTeam clinical research trial is funded by a grant from the National Institute on Aging (NIA) (R01AG076634). The clinical research trial is coordinated by the Alzheimer's Disease Cooperative Study (ADCS) at University of California San Diego School of Medicine and is led by principal investigators from the Burke Neurological Institute and Weill Cornell Medicine, Columbia University Irving Medical Center, and UC San Diego. SOURCE Burke Neurological Institute WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Late last year, geneticists made the discovery that morning sickness's most serious presentation, hyperemesis gravidarum (HG), is caused by the hormone GDF15, not human chorionic gonadotropin as previously thought. Researchers dispel common morning sickness myths and discusses potential treatments, including sensitizing people to GDF15 prior to pregnancy, similar to the way we treat allergies. Late last year, geneticist Marlena Fejzo and colleagues made the discovery that morning sickness's most serious presentation, hyperemesis gravidarum (HG), is caused by the hormone GDF15, not human chorionic gonadotropin as previously thought. In a peer-reviewed opinion article publishing May 22 in the journal Trends in Molecular Medicine, Fejzo dispels common morning sickness myths and discusses potential treatments, including sensitizing people to GDF15 prior to pregnancy, similar to the way we treat allergies. "HG can be life threatening and is associated with adverse outcomes that need to be taken seriously," says Fejzo of the Keck School of Medicine of the University of Southern California. "Now that we know that GDF15 is the most likely cause of HG, we are on the cusp of having treatments that target this hormonal pathway and end the suffering." Myth 1: Severe morning sickness is harmless and normal Pregnant people with HG are essentially starving, Fejzo says, and an increasing number of studies have demonstrated that this has serious short- and long-term clinical implications for both the parent and child. HG is a top predictor of postnatal depression, and 26% of pregnant people with HG report suicidal ideation while 18% meet the full criteria for post-traumatic stress disorder. For the child, HG is associated with preterm birth, low birth weight, and later in life, autism spectrum disorder, ADHD, depression, social problems, in addition to an increased risk of childhood cancer and respiratory and cardiovascular disease. Still, pregnant people with the condition are often dismissed by their clinicians and families. "It really is like a teratogen in pregnancy, a factor which interferes with normal fetal development, but it's still not taken seriously by a lot of medical professionals," Fejzo says. "A lot of people are brushed off and told, 'oh that's normal, it's okay, just don't take your pre-natal vitamins; you don't need them.'" At its most extreme, individuals with HG can develop Wernicke encephalopathy, a life-threatening swelling of the brain due to thymine (vitamin B1) deficiency. Since individuals with HG can have trouble even swallowing vitamins, the American College of Obstetricians and Gynecologists currently recommends that they replace broad spectrum prenatal vitamins with folic acid, but Fejzo warns that this is likely insufficient, and that thiamine supplementation is also warranted for individuals with HG. "I believe all women who have hyperemesis should be given vitamin B1 to avoid this serious brain swelling that can lead to permanent brain damage and often leads to fetal death," Fejzo says. Myth 2: Morning sickness is caused by human chorionic gonadotropic hormone (hCG) or is psychosomatic Though it was long thought that morning sickness is caused by hCG, the recent breakthrough has shown that HG's main cause is actually the hormone GDF15, which is part of a normal stress response. Usually, GDF15 is expressed only in very small amounts, but during early pregnancy it spikes by a huge amount, then wanes, and finally rises again during the third trimester. A recent Nature study co-authored by Fejzo showed that individuals who suffer from HG can have genetic variants that causes them to have lower levels of circulating GDF15 prior to pregnancy, which makes them extra sensitive when they become pregnant and are suddenly exposed to high levels. This finding has clinical implications for preventing and treating HG, since preliminary research suggests that it might be safe to manipulate GDF15 during or even prior to pregnancy. "GDF15 may be safe to manipulate in pregnancy or even prior to pregnancy," says Fejzo. "If we can increase levels of GDF15 before someone becomes pregnant, that might desensitize them, similar to how we try to desensitize people to allergens who have severe allergies," says Fejzo. "And during pregnancy, we may be able to minimize or get rid of symptoms by blocking GDF15 or its receptors in the brain stem." Myth 3: Only humans experience morning sickness Nausea and appetite loss during gestation is not a uniquely human trait -- these symptoms have been observed throughout the animal kingdom, from monkeys, dogs, and cats, to chickens, vipers, and octopuses. "I always think it's interesting that the recommendation for cats is that if they're unable to eat for a day, you should contact your veterinarian, but we don't have that recommendation out there for women with hyperemesis," says Fejzo. "If you call your doctor's office and say you haven't eaten for a day, they'll say, 'that's normal' and won't do anything. There's more proactive care for cats than humans." In addition to preventing ingestion of harmful foods, Fejzo speculates that pregnancy-induced nausea likely evolved to prevent dangerous foraging trips. "This condition likely evolved because it was probably beneficial to avoid going out searching for food during pregnancy," says Fejzo. "That may still be true for animals, but people don't need this anymore, so let's end the suffering once and for all if we can." Now, Fejzo is working toward developing and testing the proposed GDF15-based treatments. She also plans to investigate other genes and variants of GDF15 that might contribute to HG.

Vitamin B1 is an essential micronutrient for human beings. Its deficiency is the cause of numerous diseases of the nervous and cardiovascular systems. Researchers have achieved a significant advance in the fight against vitamin B1 deficiency, frequently associated with a rice-based diet. By specifically targeting the nourishing tissues of the rice grain, the scientists have succeeded in considerably increasing its vitamin B1 content, without compromising agronomic yield. These results could help solve a major public health problem in regions where rice is the staple food. Vitamin B1 is an essential micronutrient for human beings. Its deficiency is the cause of numerous diseases of the nervous and cardiovascular systems. Researchers at the University of Geneva (UNIGE), in collaboration with teams at ETH Zurich and Taiwan's National Chung Hsing University (NCHU), have achieved a significant advance in the fight against vitamin B1deficiency, frequently associated with a rice-based diet. By specifically targeting the nourishing tissues of the rice grain, the scientists have succeeded in considerably increasing its vitamin B1content, without compromising agronomic yield. These results, to be read in the Plant Biotechnology Journal, could help solve a major public health problem in regions where rice is the staple food. Most vitamins cannot be produced by the human body and must be supplied by the diet. When the diet is varied, vitamin requirements are generally covered. But in populations where cereals such as rice are the main or even the only food source, deficiencies are common. This is particularly true of vitamin B1 (thiamine), a deficiency of which causes numerous nervous and cardiovascular diseases, such as beriberi. Vitamin B1 in rice is lost during processing Rice is the staple crop for half the world's population, particularly in the tropical countries of Asia, South America and Africa. Rice grains are low in vitamin B1, and processing steps such as polishing (i.e. removing the bran by grating the peripheral layers) reduce it even further, taking 90% with them. This practice thus further aggravates chronic deficiencies. The laboratory of Teresa Fitzpatrick, full professor in the Department of Plant Sciences at the UNIGE Faculty of Science, specializes in vitamin biosynthesis and degradation pathways in plants. Her group, in collaboration with a team from ETH Zurich and Taiwan's NCHU, focused on improving vitamin B1 content in the endosperm of rice, i.e. the nourishing tissue that makes up the bulk of the seed, and therefore of what is eaten. ''Previous attempts at biofortification by other teams had succeeded in increasing the vitamin B1 content of the leaves and bran -- the outer layer of rice grains -- but not that of the ready-to-eat rice grain. In our study, we specifically targeted the increase in vitamin B1 content in the endosperm,'' explains Teresa Fitzpatrick, first author of the study. The scientists generated rice lines that express a gene that sequesters vitamin B1 in a controlled manner in the endosperm tissues. After growing in glasshouses, harvesting and polishing the rice grains, they found that the vitamin B1 content was increased in rice grains from these lines. Promising experimental crops The lines were then seeded in an experimental field in Taiwan and grown for several years. From an agronomic point of view, the characteristics analyzed were the same for both modified and unmodified rice plants. Plant height, number of stems per plant, grain weight and fertility were all comparable. On the other hand, the level of vitamin B1 in rice grains, after the polishing stage, is multiplied by 3 to 4 in the modified lines. This modification therefore enables vitamin B1 accumulation without impacting yield. ''Most studies of this type are carried out with glasshouse grown crops. The fact that we have been able to grow our lines under real field conditions, that the expression of the modified gene is stable over time without any of the agronomic characteristics being affected, is very promising,'' enthuses Wilhelm Gruissem, Professor emeritus at ETH Zurich and Distinguished Chair Professor and Yushan Fellow at NCHU. A 300-gram bowl of rice from this crop provides around a third of the recommended daily intake of vitamin B1 for an adult. The next step towards the goal of biofortified plants with vitamin B1 will be to pursue this approach in commercial varieties. However, regulatory steps relating to biofortification by genetic engineering will have to be taken before these plants could be cultivated.