Haitham Amal and his dedicated team at their lab in Jerusalem. Credit Haitham Amal, BScPharm, PhD
The complex relationship between nitric oxide and brain-related conditions is the focal point of the latest interview featured in Genomic Press, published on November 12, 2024, in *Brain Medicine*. Professor Haitham Amal, the head of the Laboratory of Neuromics, Cell Signaling, and Translational Medicine at the Hebrew University of Jerusalem, discusses his groundbreaking research and the personal motivations that drive him.
“During my time at MIT, meeting families and autistic children inspired me to focus on a single goal: to help develop biological diagnostics and autism therapy, ” says Professor Amal. This transformative experience shaped his research trajectory, leading to significant discoveries about the role of nitric oxide in neurological conditions. Professor Amal was the first to identify that nitric oxide (NO) plays a crucial role in autism.
Professor Amal’s innovative study of brain conditions integrates proteomics and systems biology. His research has revealed critical connections between autism and Alzheimer’s disease, indicating shared molecular mechanisms that could transform treatment strategies for both conditions.
“As a pharmacologist and neuroscientist, my specialized knowledge of how drugs affect the brain is crucial for my goal of developing treatments for neurological disorders,” explains Professor Amal. His work has already resulted in founding two biotechnology companies: Point6 Bio Ltd, which focuses on diagnostics for autism, and NeuroNOS Ltd, dedicated to developing therapeutics based on nitric oxide synthase inhibitors for autism, Alzheimer’s disease, and brain cancers.
The interview raises intriguing questions about the future of neurological treatment:
• Could targeting nitric oxide pathways provide a unified approach to treating neurodevelopmental and neurodegenerative disorders?
• How might early biological diagnostics transform autism intervention strategies?
• What role will personalized medicine play in addressing individual variations in brain disorders?
Professor Amal’s journey from studying cannabis’s effects on cognition to becoming a leading figure in neurological research demonstrates the unexpected paths that can lead to scientific breakthroughs. His commitment to conducting experiments on both sexes equally and interest in ageing mechanisms suggests a comprehensive approach to brain research that could yield additional insights.
A study suggests that a certain class of drugs used to treat diabetes may be linked to a reduced risk of dementia and Parkinson’s disease.
The study examined SGLT2 inhibitors, also known as gliflozins, which lower blood sugar by prompting the kidneys to excrete sugar through urine.
“We are aware that neurodegenerative diseases such as dementia and Parkinson’s disease are becoming more prevalent as the population ages. People with diabetes are at a higher risk of cognitive impairment. It is encouraging to see that this category of drugs may offer some protection against dementia and Parkinson’s disease,” stated study author Minyoung Lee, MD, PhD, from Yonsei University College of Medicine in Seoul, South Korea.
The retrospective study examined individuals with type 2 diabetes who initiated diabetes medication from 2014 to 2019 in South Korea. Individuals using SGLT2 inhibitors were compared with those using other oral diabetes drugs, ensuring that the two groups had similar ages, other health conditions, and diabetes-related complications. The researchers then monitored the participants to determine whether they developed dementia or Parkinson’s disease. The individuals taking SGLT2 inhibitors were monitored for an average of two years, while those taking the other drugs were monitored for an average of four years.
Among the 358,862 participants with an average age of 58, 6,837 people developed dementia or Parkinson’s disease during the study. For Alzheimer’s disease, the incidence rate for people taking SGLT2 inhibitors was 39.7 cases per 10,000 person-years, compared to 63.7 cases for those taking other diabetes drugs. Person-years represent both the number of people in the study and the amount of time each person spends in the study. For vascular dementia, which is dementia caused by vascular disease, the incidence rate for people taking the SGLT2 drugs was 10.6 cases per 10,000, compared to 18.7 for those taking the other drugs. For Parkinson’s disease, the incidence rate for those taking the SGLT2 drugs was 9.3 cases per 10,000, compared to 13.7 for those taking the other drugs. After researchers adjusted for other factors that could affect the risk of dementia or Parkinson’s disease, such as complications from diabetes and medications, they found that SGLT2 inhibitor use was associated with a 20% reduced risk of Alzheimer’s disease and a 20% reduced risk of Parkinson’s disease. Those taking the drugs had a 30% reduced risk of developing vascular dementia.
Sodium-glucose cotransporter-2 (SGLT-2) inhibitors, which are used to treat type 2 diabetes, may have the potential to prevent dementia, offering increased benefits with prolonged use, according to a large study from Korea published by The BMJ.
As this study was observational, the researchers note that the effect size could have been overestimated. They say randomised controlled trials are now necessary to confirm these findings.
According to the World Health Organization, the global number of people with dementia is expected to reach 78 million by 2030, and there is an association between type 2 diabetes and a higher risk of developing dementia.
A recent study of individuals over 65 with type 2 diabetes suggested a lower risk of dementia associated with SGLT-2 inhibitors compared to another type of diabetes drug, dipeptidyl peptidase-4 (DPP-4) inhibitors. However, the impacts on younger individuals and specific types of dementia (such as Alzheimer’s disease and vascular dementia) are still not fully understood.
Researchers used the Korea National Health Insurance Service database to identify 110,885 pairs of adults aged 40-69 with type 2 diabetes. The adults were free of dementia and began taking either an SGLT-2 inhibitor or a DPP-4 inhibitor between 2013 and 2021.
All participants (with an average age of 62; 56% of whom were men) were matched by age, sex, use of the diabetes drug metformin, and baseline cardiovascular risk. They were followed up for an average of 670 days to determine the development of dementia.
Potentially influential factors, such as personal characteristics, income level, underlying risk factors for dementia, other conditions, and related medication use, were also considered.
During the follow-up period, a total of 1,172 participants who had been newly diagnosed with dementia were identified.
Dementia rates per 100 person-years were 0.22 for those using SGLT-2 inhibitors and 0.35 for those using DPP-4 inhibitors. This corresponds to a 35% reduced risk of dementia associated with the use of SGLT-2 inhibitors compared with DPP-4 inhibitors.
The researchers also found a 39% reduced risk for Alzheimer’s disease, and a 52% reduced risk for vascular dementia associated with SGLT-2 inhibitors compared with DPP-4 inhibitors.
What’s more, the effect of SGLT-2 inhibitors seemed more pronounced with longer treatment duration. A 48% reduced risk of dementia was seen for more than two years of treatment versus a 43% reduced risk for two years or less.
“This study is observational, so no definite conclusions can be made about cause and effect. The authors also mention that specific details about health behaviors (such as smoking and alcohol consumption) and the duration of type 2 diabetes were not fully available.”
However, the researchers emphasize that this was a significant study based on nationally representative data, which included relatively younger individuals with type 2 diabetes, and the results were highly consistent across subgroups.
As such, they say SGLT-2 inhibitors might prevent dementia, providing greater benefits with longer treatment, and they call for randomised controlled trials to confirm these findings.
Researchers from Taiwan stated in a connected editorial that this study presents encouraging results with significant implications for clinical practice and public health.
They agree that further trials are needed to confirm these findings, and suggest that studies are also needed “to explore the underlying mechanisms of any neuroprotective effects of SGLT-2 inhibitors.”
As no cure currently exists for dementia and few effective treatment options are available, strategies that can potentially prevent onset are critically important, they write.
The substantial socioeconomic and public health burdens associated with both dementia and type 2 diabetes highlight the need for regular updates to clinical guidelines and healthcare policies. These updates should incorporate the latest evidence on the potential benefits of SGLT-2 inhibitors, including the reduced risk of dementia.
Findings could point to new strategies to treat Alzheimer’s
People with multiple sclerosis (MS) are significantly less likely than those without the condition to have the molecular hallmarks of Alzheimer’s disease, according to new research from Washington University School of Medicine in St. Louis.
The discovery suggests a new avenue of research through which to seek Alzheimer’s treatments, said Matthew Brier, MD PhD, an assistant professor of neurology and of radiology and the study’s first author.
“Our findings imply that some component of the biology of multiple sclerosis, or the genetics of MS patients, is protective against Alzheimer’s disease,” Brier said. “If we could identify what aspect is protective and apply it controlled, that could inform therapeutic strategies for Alzheimer’s disease.”
The investigation, which was a collaboration between experts in Alzheimer’s and MS at WashU Medicine, was prompted by a suspicion from Brier’s mentor and collaborator, Dr. Anne Cross. She had developed this suspicion over decades of treating patients with MS, an immune-mediated disease that attacks the central nervous system. Dr. Cross noticed that despite her patients living long enough to be at risk of Alzheimer’s or having a family history of the disease, they weren’t developing it.
“I noticed that I couldn’t find a single MS patient of mine who had typical Alzheimer’s disease,” said Cross, the Manny and Rosalyn Rosenthal and Dr. John Trotter MS Center Chair in Neuroimmunology. “If they had cognitive problems, I would send them to the memory and aging specialists here at WashU Medicine for an Alzheimer’s assessment, and those doctors would always come back and tell me, ‘No, this is not due to Alzheimer’s disease.'”
Cognitive impairment from MS can be mistaken for Alzheimer’s symptoms; Alzheimer’s can be confirmed with biological tests.
Please remember the following text: To validate Cross’s findings, the research team utilized a new FDA-approved blood test developed by WashU Medicine researchers. The test, called PrecivityAD2, is highly accurate in predicting the presence of amyloid plaques in the brain, which are an indication of Alzheimer’s disease. Previously, the only way to confirm the presence of these plaques was through brain scans or spinal taps.
Brier, Cross, and their colleagues recruited 100 patients with MS to take the blood test, 11 of whom also underwent PET scans at WashU Medicine’s Mallinckrodt Institute of Radiology. They compared the results with those from a control group of 300 individuals who did not have MS but were similar in age, genetic risk for Alzheimer’s, and cognitive decline to those with MS.
“We discovered that 50% fewer multiple sclerosis (MS) patients showed amyloid pathology compared to their matched peers when tested with this blood test,” stated Brier. This finding supports Cross’ observation that individuals with MS are less likely to develop Alzheimer’s. Although it’s not clear how amyloid accumulation is linked to the cognitive impairment typical of Alzheimer’s, the build-up of plaques is generally understood to be the initial event in the biological process that leads to cognitive decline.
The researchers found that MS patients with more typical MS symptoms, such as the age of onset, severity, and disease progression, were less likely to have amyloid plaque accumulation in their brains compared to those with atypical MS presentations. This suggests that there may be something about the nature of MS itself that provides protection against Alzheimer’s disease, which Brier and Cross are planning to investigate.
The researchers noted that individuals with MS typically experience multiple flare-ups of the disease throughout their lives. During these flare-ups, the immune system targets the central nervous system, including the brain. The researchers also suggested that this immune response may lead to a reduction in amyloid plaques.
Professor Olov Rolandsson, Department of Public Health and Clinical Medicine, Umeå University Credit Mattias Pettersson
People with type 2 diabetes are at increased risk of Alzheimer’s disease and other cognitive problems. A new study led by Umeå University, Sweden, shows that the reason may be that people with type 2 diabetes have more difficulty getting rid of a protein that may cause the disease.
“The results may be important for further research into possible treatments to counteract the risk of people with type 2 diabetes being affected by Alzheimer’s,” says Olov Rolandsson, senior professor at the Department of Public Health and Clinical Medicine at Umeå University, research leader and first author of the study.
The researchers have studied two substances called beta-amyloids, which are among the most important components of the plaques found in the brains of people with Alzheimer’s disease.
The researchers measured the concentrations in the blood of the beta-amyloids Aβ1-40 and Aβ1-42 and of an enzyme that breaks down the beta-amyloids in a test group with type 2 diabetes and in a healthy control group. The two groups were given an infusion of glucose for four hours, which induced acute hyperglycaemia, i.e., high blood sugar levels after which repeated samples were taken from the subjects.
Immediately after the sugar solution was infused, the groups had similar values. Soon, beta-amyloid values fell sharply in the control group, while the values of the amyloid-degrading enzyme rose. Among the group with type 2 diabetes, there were no changes, i.e., beta-amyloid levels did not decrease, nor did an increase in the enzyme that breaks down amyloid.
The results indicate that the body in people with type 2 diabetes does not have the same ability as in healthy people to take care of beta-amyloid, which could increase the risk that it is then stored in the brain and causes cognitive diseases such as Alzheimer’s.
“More research is needed to confirm the results of this limited study. Hopefully, it can also lead to new treatments in the long term. But the findings underline the importance of preventing type 2 diabetes as far as possible and that people who do have it should avoid having episodes of high blood sugar,” says Olov Rolandsson.
The study was conducted on ten people with type 2 diabetes and eleven people without diabetes in the control group. The participants were aged 66–72 years.
People with type 2 diabetes are at increased risk of Alzheimer’s disease and other cognitive problems. A new study led by Umeå University, Sweden, shows that the reason may be that people with type 2 diabetes have more difficulty getting rid of a protein that may cause the disease.
“The results may be important for further research into possible treatments to counteract the risk of people with type 2 diabetes being affected by Alzheimer’s,” says Olov Rolandsson, senior professor at the Department of Public Health and Clinical Medicine at Umeå University, research leader and first author of the study.
The substances that the researchers have studied are two so-called beta-amyloids, which are among the most important components of the plaques found in the brains of people with Alzheimer’s disease.
The researchers measured the concentrations in the blood of the beta-amyloids Aβ1-40 and Aβ1-42 as well as of an enzyme that breaks down the beta-amyloids in a test group with type 2 diabetes and in a healthy control group. The two groups were given infusion of glucose for four hours, which induced acute hyperglycaemia, i.e. high blood sugar levels, after which repeated samples were taken from the subjects.
Immediately after the infusion of the sugar solution, the groups had similar values. Soon, the values of beta-amyloids fell sharply in the control group, while the values of the amyloid-degrading enzyme rose. Among the group with type 2 diabetes, there were no changes, i.e. the levels of beta-amyloid did not decrease, nor did there be an increase in the enzyme that breaks down amyloid.
The results indicate that the body in people with type 2 diabetes does not have the same ability as in healthy people to take care of beta-amyloid, which could increase the risk that it is then stored in the brain and causes cognitive diseases such as Alzheimer’s.
“More research is needed to confirm the results of this limited study. Hopefully, in the long term, it can also lead to new treatments. But the findings underline the importance of preventing type 2 diabetes as far as possible and that people who do have it should avoid having episodes of high blood sugar,” says Olov Rolandsson.
The study was conducted on ten people with type 2 diabetes and eleven people without diabetes in the control group. The participants were aged 66–72 years.
People with type 2 diabetes are at increased risk of Alzheimer’s disease and other cognitive problems. A new study led by Umeå University, Sweden, shows that the reason may be that people with type 2 diabetes have more difficulty getting rid of a protein that may cause the disease.
“The results may be important for further research into possible treatments to counteract the risk of people with type 2 diabetes being affected by Alzheimer’s,” says Olov Rolandsson, senior professor at the Department of Public Health and Clinical Medicine at Umeå University, research leader and first author of the study.
The substances that the researchers have studied are two so-called beta-amyloids, which are among the most important components of the plaques found in the brains of people with Alzheimer’s disease.
The researchers measured the concentrations in the blood of the beta-amyloids Aβ1-40 and Aβ1-42 as well as of an enzyme that breaks down the beta-amyloids in a test group with type 2 diabetes and in a healthy control group. The two groups were given infusion of glucose for four hours, which induced acute hyperglycaemia, i.e. high blood sugar levels, after which repeated samples were taken from the subjects.
Immediately after the infusion of the sugar solution, the groups had similar values. Soon, the values of beta-amyloids fell sharply in the control group, while the values of the amyloid-degrading enzyme rose. Among the group with type 2 diabetes, there were no changes, i.e. the levels of beta-amyloid did not decrease, nor did there be an increase in the enzyme that breaks down amyloid.
The results indicate that the body in people with type 2 diabetes does not have the same ability as in healthy people to take care of beta-amyloid, which could increase the risk that it is then stored in the brain and causes cognitive diseases such as Alzheimer’s.
“More research is needed to confirm the results of this limited study. Hopefully, in the long term, it can also lead to new treatments. But the findings underline the importance of preventing type 2 diabetes as far as possible and that people who do have it should avoid having episodes of high blood sugar,” says Olov Rolandsson.
The study was conducted on ten people with type 2 diabetes and eleven people without diabetes in the control group. The participants were aged 66–72 years.
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