Innovative gene therapy 'reprograms' cells to reverse neurological deficiencies
2021-07-12
(Press-News.org) A novel method of gene therapy is helping children born with a rare genetic disorder called AADC deficiency that causes severe physical and developmental disabilities. The study, led by researchers at The Ohio State University Wexner Medical Center and The Ohio State University College of Medicine, offers new hope to those living with incurable genetic and neurodegenerative diseases.
Research findings are published online in the journal Nature Communications.
This study describes the findings from the targeted delivery of gene therapy to midbrain to treat a rare deadly neurodevelopmental disorder in children with a neurogenetic disease, aromatic L-amino acid decarboxylase (AADC) deficiency characterized by deficient synthesis of dopamine and serotonin.
Only about 135 children worldwide are known to be missing the enzyme that produces dopamine in the central nervous system, which fuels pathways in the brain responsible for motor function and emotions. Without this enzyme, children lack muscle control, and are usually unable to speak, feed themselves or even hold up their head. They also suffer from seizure-like episodes called oculogyric crises that can last for hours.
"Remarkably, these episodes are the first symptom to disappear after gene therapy surgery, and they never return," said study co-author Dr. Krystof Bankiewicz, professor of neurological surgery at Ohio State College of Medicine who leads the Bankiewicz Lab. "In the months that follow, many patients experience life-changing improvements. Not only do they begin laughing and have improved mood, but many are able to begin speaking and even walking. They are making up for the time they lost during their abnormal development."
The directed gene therapy in seven children ages 4 to 9 who were infused with the viral vector resulted in dramatic improvement of symptoms, motor function and quality of life. Six children were treated at UCSF Benioff Children's Hospital in San Francisco and one at Ohio State Wexner Medical Center. This therapeutic modality promises to transform the treatment of AADC deficiency and other similar disorders of the brain in the future, Bankiewicz said.
During the gene therapy surgery, physicians infuse a benign virus programmed with specific DNA into precisely targeted areas of the brain. The infusion is delivered extremely slowly as surgeons monitor exactly how it spreads within the brain using real-time MRI imaging.
"Really, what we're doing is introducing a different code to the cell," said Dr. James "Brad" Elder, director of neurosurgical oncology at Ohio State Wexner Medical Center's Neurological Institute. "And we're watching the whole thing happen live. So we continuously repeat the MRI and we can see the infusion blossom within the desired nucleus."
Researchers believe this same method of gene therapy can be used to treat other genetic disorders as well as common neurodegenerative diseases, such as Parkinson's and Alzheimer's disease. Clinical trials are underway to test this procedure in others living with debilitating and incurable neurological conditions.
The directed gene therapy, in these patients, resulted in dramatic improvement of symptoms, motor function and quality of life. This therapeutic modality promises to transform the treatment of AADC deficiency and other similar disorders of the brain in the future.
INFORMATION:
The findings described in this study are the culmination of decades of work by teams from multiple academic institutions, including University of California San Francisco, Washington University in St. Louis, Medical Neurogenetics Laboratory in Atlanta, St. Louis Children's Hospital and Nationwide Children's Hospital in Columbus, Ohio.
The research was supported by the National Institute of Neurological Disorders and Stroke and foundational grants, including the AADC Research Trust, the Pediatric Neurotransmitter Disease Association and funding from The Ohio State University.
"This work provides a framework for the treatment of other human nervous system genetic diseases. It's our hope that this will be the first of many ultra-rare and other neurologic disorders that will be treated with gene therapy in a similar manner," Bankiewicz said.
ELSE PRESS RELEASES FROM THIS DATE:
2021-07-12
USC researchers have achieved a better way to identify elusive DNA variants responsible for genetic changes affecting cell functions and diseases.
Using computational biology tools, scientists at the university's Dornsife College of Letters, Arts and Sciences studied "variable-number tandem repeats" (VNTR) in DNA. VNTRs are stretches of DNA made of a short pattern of nucleotides repeated over and over, like a plaid pattern shirt. Though they comprise but 3% of the human genome, the repetitive DNA governs how some genes are encoded and levels of proteins are produced in a cell, and account for most of the structural variation.
Current methods do not accurately detect the variations in genes in some repetitive ...
2021-07-12
Scientists have produced the first fine-detail molecular blueprints of a bacterial enzyme known as Lit, which is suspected to play a "stealthy" role in the progression of infection by reducing the immune response.
Blueprints such as these allow drug designers to uncover potential weaknesses in bacterial arsenals as they seek to develop new therapeutics that may help us win the war against antibiotic resistance.
The study, led by scientists from the School of Biochemistry and Immunology and the Trinity Biomedical Sciences Institute (TBSI) at Trinity College Dublin, has just been published by leading international journal Nature Communications.
Lipoproteins and their role in ...
2021-07-12
Sclerosis, Parkinson's Disease, Alzheimer's and epilepsy are but a few of the central nervous system disorders. They are also very difficult to treat, since the brain is protected by the blood-brain barrier.
The blood-brain barrier works as a border wall between the blood and the brain, allowing just certain molecules to enter the brain. And whereas water and oxygen can get through, as can other substances such as alcohol and coffee. But it does block more than 99 percent of potentially neuroprotective compounds from reaching their targets in the brain.
Now, ...
2021-07-12
In 2015, 170 countries worldwide adopted the Paris Agreement, with the goal limiting the average global temperature increase to 1.5°C. Following the agreement, many countries and cities proposed targets for greenhouse gas mitigation. However, the UNEP Emissions Gap Report 2020 shows that, without drastic and strict actions to mitigate the climate crisis, we are still heading for a temperature increase of more than 3°C by the end of the 21st century.
A new study published in the journal Frontiers in Sustainable Cities presents the first global balance sheet of greenhouse gasses (GHGs) emitted by major cities around the world. The aim was to research and monitor the effectiveness of historical GHG reduction ...
2021-07-12
A new study published by Wiley early online in CANCER, a peer-reviewed journal of the American Cancer Society, has identified unmet social needs in women with gynecologic cancer that could be addressed to improve care for patients and lessen disparities. For example, identifying patients who reported needing help with reading hospital materials resulted in the use of a cancer care navigator who provided patient education and support, facilitating physician-patient communication and adherence to care recommendations.
The prospective survey-based ...
2021-07-12
Oncotarget published "Inhibitory effects of Tomivosertib in acute myeloid leukemia" which reported that the authors evaluated the therapeutic potential of the highly-selective MNK1/2 inhibitor Tomivosertib on AML cells.
Tomivosertib was highly effective at blocking eIF4E phosphorylation on serine 209 in AML cells.
Moreover, combination of Tomivosertib and Venetoclax resulted in synergistic anti-leukemic responses in AML cell lines.
Mass spectrometry studies identified novel putative MNK1/2 interactors, while in parallel studies we demonstrated that MNK2 - RAPTOR - mTOR complexes are not disrupted by Tomivosertib.
Overall, these Oncotarget findings demonstrate that Tomivosertib exhibits potent ...
2021-07-12
Oncotarget published "Epigallocatechin-3-gallate modulates Tau Post-translational modifications and cytoskeletal network" which reported that the chemical modulators of Tau PTMs, such as kinase inhibitors and antibody-based therapeutics, have been developed, but natural compounds, as modulators of Tau PTMs are not much explored.
These authors applied biophysical and biochemical techniques like fluorescence kinetics, oligomerization analysis and transmission electron microscopy to investigate the impact of EGCG on Tau glycation in vitro.
EGCG inhibited methyl glyoxal -induced Tau glycation in vitro.
EGCG potently inhibited MG-induced advanced glycation endproducts formation in neuroblastoma cells as well modulated the localization ...
2021-07-12
Oncotarget published "A novel E2F1-regulated lncRNA, LAPAS1, is required for S phase progression and cell proliferation" which reported that long non-coding RNAs are major regulators of many cellular processes, including cell cycle progression and cell proliferation.
Inhibition of LAPAS1 expression increases the percentage of S phase cells, and its silencing in synchronized cells delays their progression through S phase.
In agreement with its suggested role in cell cycle progression, prolonged inhibition of LAPAS1 attenuates proliferation of human cancer cells.
Importantly, knockdown of SPNS2 rescues the effect of LAPAS1 silencing on cell cycle ...
2021-07-12
Imagine sitting out in the sun, reading a digital screen as thin as paper, but seeing the same image quality as if you were indoors. Thanks to research from Chalmers University of Technology, Sweden, it could soon be a reality. A new type of reflective screen - sometimes described as 'electronic paper' - offers optimal colour display, while using ambient light to keep energy consumption to a minimum.
Traditional digital screens use a backlight to illuminate the text or images displayed upon them. This is fine indoors, but we've all experienced the difficulties of viewing such screens in bright sunshine. Reflective screens, however, attempt to use the ambient light, mimicking the way our eyes ...
2021-07-12
Researchers have identified a specialized protein that appears to help prevent tumor cells from entering the bloodstream and spreading to other parts of the body.
"We have discovered that this protein, TRPM7, senses the pressure of fluid flowing in the circulation and stops the cells from spreading through the vascular system," said Kaustav Bera, a Johns Hopkins University PhD candidate in chemical and biomolecular engineering and a lead author of the study, which was done with colleagues at the University of Alberta and Universitat Pompeu Fabra.
"We found that metastatic tumor cells have markedly reduced levels of this sensor protein, and that is why they ...
LAST 30 PRESS RELEASES:
[Press-News.org] Innovative gene therapy 'reprograms' cells to reverse neurological deficiencies
