image:
Researchers create mini-brains from skin cells in the lab. The mini-brains are used to test out medicines and gene therapy. The work has provided new knowledge and ideas for the treatment of patients with childhood dementia, Alzheimer's, ALS, Parkinson's and DOOR syndrome.
Credit: Julie Gloppe Solem, NTNU
A lot of research has been done over many decades on diseases that are widespread in large parts of the population, such as cancer and heart disease. As a result, treatment methods have improved enormously thanks to long-term research efforts on diseases that affect many people.
However, there are many diseases that affect just a handful people. These diseases often fly under the radar and are far less researched. They include quite a few rare, hereditary diseases, such as DOOR syndrome, which is especially found in Canada and the Middle East.
A team of scientists is now in the process of trying to change this.
For some hereditary, rare diseases, there is currently no cure. However, gene therapy is a possible solution, and we are now testing various strategies using gene therapy, says Magnar Bjrs, a professor at the Norwegian University of Science and Technology(NTNU's) Department of Clinical and Molecular Medicine.
He has established a research team at NTNU and Oslo University Hospital that conducts basic research on rare, hereditary diseases with a long-term goal of finding new therapies.
One of the rare diseases for which there is currently no medication or treatment is called DOOR syndrome.
This is a congenital disorder that involves multiple abnormalities. DOOR is an acronym for the main features of the disorder: Deafness, Onychodystrophy (short or absent nails), Osteodystrophy (short fingers and toes) and developmental delay and intellectual disability (previously called mental Retardation).
DOOR syndrome is hereditary and is caused by the lack of a specific protein in the genes called OXR1 (OXidation Resistance gene 1).
Due to lack of this protein, the brain cells are unable to develop as they should. As a result, the brain cells either become dysfunctional or simply die, says Magnar Bjrs.
In order to investigate whether there is a way to prevent this from happening, the Bjrs team has carried out tests inside mini-brains that they grow in their lab.
The Bjrs team has been working on growing mini-organs such as mini-brains, mini-lungs and mini-eyes since 2018. The scientists use the mini-organs to test drugs and gene therapy.
In order to grow mini-brains for their research on DOOR syndrome, the research team needed cells from people who have this disease.
A number of cases have been registered in Canada and the Middle East, and the research being done in Norway is based on skin cells from people who have DOOR syndrome.
In the laboratory, we have transformed the skin cells into embryo cells. We have reversed the development in the skin cells so that they return to the foetal stage and become like the first cells that form in humans. We have then used these stem cells to create mini-brains, says Bjrs.
Using skin cells from people with DOOR syndrome, the scientists have recreated the disease in the mini-brains. They can then use these mini-brains to test out therapies for this disease.
The process of developing mini-brains takes several months and is painstaking and expensive.
The work has given the scientists insight into the reasons why patients develop disease and thus also ideas for treatment strategies. Gene therapy is one possible treatment where the brain cells can be made to start producing the missing protein.
A virus is actually used as a messenger that delivers the necessary production information to the brain cells.
As a follow-up to our published work, we are now testing virus-based gene therapy as a treatment for this disease," Bjrs said. "We create a harmless virus in the lab and then put a healthy OXR1 gene into the virus genome, and this gene has the ability to produce the protein that brain cells lack in people with DOOR syndrome."
The virus is then injected into the mini-brains.
The virus is absorbed into the brain and brain cells. The gene introduced into the brain cells via the virus can then begin to produce the missing protein," he said. "If this protein can be overproduced, it helps to stop and, at best, reverse the disease. In order to treat DOOR syndrome, patients will need to start gene therapy at a very early stage, probably as soon as the first symptoms of disease are noticed."
Gene therapy research has evolved greatly over the past 20 years.
In 2007, only one clinical trial of gene therapy took place. Today, there are thousands of clinical trials involving gene therapy,Bjrs said.
The research has not only provided new knowledge and ideas for the treatment of patients with DOOR syndrome, but also for other diseases.
What is particularly interesting about the OXR1 protein that patients with DOOR syndrome lack is that this gene therapy method also has an interesting potential for treating other diseases, says Bjrs.
The OXR1 protein reduces inflammation, which is a characteristic of most degenerative diseases of the brain, such as childhood dementia, Alzheimers, ALS and Parkinsons.
The researchers have used new, advanced technology. The mini-brains that they have grown are made from skin cells from DOOR syndrome patients and from healthy individuals.
The mini-brains have been used to study brain development and the scientists have created different parts of the brain that control different functions, such as memory, learning, motor skills, fluid balance, hormone balance and temperature control.
It has been shown for the first time in a human model that OXR1 promotes protein methylation during brain development in space and time. Protein methylation is one of several important chemical processes that control gene expression.
The study provides new insights into pathological traits associated with OXR1 deficiency in patients.
References: Genome Biology. A loss-of-function mutation in human Oxidation Resistance 1 disrupts the spatialtemporal regulation of histone arginine methylation in neurodevelopment
https://genomebiology.biomedcentral.com/articles/10.1186/s13059-023-03037-1
Experimental study
Cells
A loss-of-function mutation in human Oxidation Resistance 1 disrupts the spatialtemporal regulation of histone arginine methylation in neurodevelopment
29-Sep-2023
Continue reading here:
New therapy can treat rare and hereditary diseases - EurekAlert
- Podcast 9 Athens part 3 and news - November 8th, 2009 [November 8th, 2009]
- Podcast 10 Athens part 4 - November 8th, 2009 [November 8th, 2009]
- Podcast 11 Athens Part 5 - November 8th, 2009 [November 8th, 2009]
- Episode 12 Cardiac Nuclear Medicine in the UK - November 8th, 2009 [November 8th, 2009]
- Podcast 13 Choline PET and prostate cancer - November 8th, 2009 [November 8th, 2009]
- Episode14 ED function and Dysponea - November 8th, 2009 [November 8th, 2009]
- ep 15 Collimator Choice and Reconstruction algorithm - November 8th, 2009 [November 8th, 2009]
- Episode 16 Dr Strauss on vulnerable plaque - November 8th, 2009 [November 8th, 2009]
- Episode17 Chemical Stress - November 8th, 2009 [November 8th, 2009]
- Episode 18 Myocardial Perfusion Imaging and Diabetes - November 8th, 2009 [November 8th, 2009]
- Episode 19 The INSPIRE trial - November 8th, 2009 [November 8th, 2009]
- 20 Dual isotope with a difference - November 8th, 2009 [November 8th, 2009]
- Episode 21 The real effect of stress - November 8th, 2009 [November 8th, 2009]
- Episode 22 D-SPECT - November 8th, 2009 [November 8th, 2009]
- Episode 23 VQ Reprise - November 8th, 2009 [November 8th, 2009]
- Episode 24 Hepatobiliary Nuclear Medicine - November 8th, 2009 [November 8th, 2009]
- Episode 25 Sleep Apnea - November 8th, 2009 [November 8th, 2009]
- Episode 26 Imaging Post Traumatic Stress Disorder - November 8th, 2009 [November 8th, 2009]
- Episode 27 Cardiac Stem Cells - November 8th, 2009 [November 8th, 2009]
- Episode 28 Molly Supply - November 8th, 2009 [November 8th, 2009]
- Episode 29 Melanoma therapy interview with Dr Ekaterina Dadachova - November 8th, 2009 [November 8th, 2009]
- Episode 30 Viral Therapy - November 8th, 2009 [November 8th, 2009]
- Episode 31 breast radiotherapy using radioisotopes - November 8th, 2009 [November 8th, 2009]
- Episode 32 news from snm - November 8th, 2009 [November 8th, 2009]
- Episode 33 EBV Imaging and Therapy - November 8th, 2009 [November 8th, 2009]
- Episode 34 Dr Lele SNM India 2009 - December 14th, 2009 [December 14th, 2009]
- Episode 35 Dr Andrew Scott from the Ludwig institute - January 10th, 2010 [January 10th, 2010]
- Episode 36 CardiArc - February 25th, 2010 [February 25th, 2010]
- Episode 37 Dr Modder Radiosynoviorthesis (Radiation Synovectomy) - March 31st, 2010 [March 31st, 2010]
- Episode 38 Indian Nuclear Medicine With Dr Malhotra and Dr Krishna - May 28th, 2010 [May 28th, 2010]
- Episode 39 Prof Ora Israel The Utility of Hybrid Imaging - July 13th, 2010 [July 13th, 2010]
- Episode 40 New V/Q SPECT developments - October 11th, 2010 [October 11th, 2010]
- Episode 41 scintimun - February 14th, 2011 [February 14th, 2011]
- Episode 42 Radio-Isotope Supply into the future - March 6th, 2011 [March 6th, 2011]
- Podcast 4: DNA therapy - April 24th, 2011 [April 24th, 2011]
- Sorry about the delay a new podcast will be out soon! - April 24th, 2011 [April 24th, 2011]
- Podcast 5 Flash 3D - April 24th, 2011 [April 24th, 2011]
- Podcast 6 Affibody - April 24th, 2011 [April 24th, 2011]
- Podcast 7 EANM 2006 Athens Part 1 - April 24th, 2011 [April 24th, 2011]
- Podcast 8 Athens Part 2 - April 24th, 2011 [April 24th, 2011]
- Episode 43 Rapidscan Part 1, 720P high quality video version - May 1st, 2011 [May 1st, 2011]
- Episode 43 Rapidscan Part 1, Ipod quality video - May 1st, 2011 [May 1st, 2011]
- Episode 43 Rapidscan Part 1, Audio version - May 1st, 2011 [May 1st, 2011]
- Episode 45 Mummies with cardiovascular disease video - May 21st, 2011 [May 21st, 2011]
- Episode 45 Mummies with cardiovascular disease audio edition - May 21st, 2011 [May 21st, 2011]
- Episode 46 Dr Gordon DePuey Choosing Reconstruction clinical perspective - August 7th, 2011 [August 7th, 2011]
- Episode 46 Dr Gordon DePuey Choosing Reconstruction clinical perspective audio version - August 7th, 2011 [August 7th, 2011]
- Episode 47 Cardiac Image Fusion With Dr Kaufmann - September 18th, 2011 [September 18th, 2011]
- Episode 47 Cardiac Fusion with Dr Kaufmann video version - September 18th, 2011 [September 18th, 2011]
- Dear Steve, I am and many more like me are your one more thing. - October 9th, 2011 [October 9th, 2011]
- EPISODE 48 PET MRI camera from Siemens with Dr Georgi audio - October 23rd, 2011 [October 23rd, 2011]
- EPISODE 48 PET MRI camera from Siemens Dr Georgi video - October 23rd, 2011 [October 23rd, 2011]
- Silicon Biosystems to Present Single-Circulating Tumor Cell Molecular Characterization at the Fourth World CTC Summit - April 25th, 2012 [April 25th, 2012]
- Leukaemia cells have a remembrance of things past - April 25th, 2012 [April 25th, 2012]
- Technologist Education Requirements Can Help Cut Repeat Scans - April 25th, 2012 [April 25th, 2012]
- HKU Collaborative Research Discovers A Novel Molecular Mechanism Of A New Anti-HIV-1 Drug Candidate - April 25th, 2012 [April 25th, 2012]
- Focal Segmental Glomerulosclerosis and the Nephrotic Syndrome - Part 1 Clinical - Video - May 4th, 2012 [May 4th, 2012]
- Electro-Medicine : Biological Physics - The Molecular Basis of Alzheimers Disease - Video - May 4th, 2012 [May 4th, 2012]
- osdd heterocyclic compounds and molecular medicines - Video - May 4th, 2012 [May 4th, 2012]
- Molecule to Medicine: The Biomarker Frontier - Video - May 4th, 2012 [May 4th, 2012]
- Fulfilling the Promise of Molecular Medicine in a Developmental Brain Disorder - Video - May 4th, 2012 [May 4th, 2012]
- Focus on Stefanie Dimmeler - Video - May 4th, 2012 [May 4th, 2012]
- Dundee - May 4th, 2012 [May 4th, 2012]
- Nanotechnology In Medicine: Huge Potential, But What Are The Risks? - May 5th, 2012 [May 5th, 2012]
- Cutting Edge Technology Coming To DMH - May 5th, 2012 [May 5th, 2012]
- This Week in Experimental and Molecular Pathology - May 5th, 2012 [May 5th, 2012]
- Researchers' discovery offers hope for cancer, heart disease miracle drugs - May 7th, 2012 [May 7th, 2012]
- Penn State student Zachary Hostetler from Garnet Valley is being honored as a student marshal - May 7th, 2012 [May 7th, 2012]
- NCKU Student Wins Prestigious Award for Anti-Cancer Research - May 10th, 2012 [May 10th, 2012]
- In-Vitro Diagnostics (IVD) Market (Clinical Chemistry, Immunoassays, Molecular Diagnostics, Hematology Analyzers ... - May 10th, 2012 [May 10th, 2012]
- Pitt team uses genomics to identify a molecular-based treatment for a viral skin cancer - May 10th, 2012 [May 10th, 2012]
- Genomics used to identify a molecular-based treatment for a viral skin cancer - May 10th, 2012 [May 10th, 2012]
- 2 molecular biologists get $500K medical prize - May 13th, 2012 [May 13th, 2012]
- 2 molecular biologists share $500K medical prize - May 13th, 2012 [May 13th, 2012]
- Lab21 Unveils New Molecular Analysis Services at Greenville Site - May 13th, 2012 [May 13th, 2012]
- 2 molecular biologists from NYC to share $500K medical prize for pioneering research on cells - May 13th, 2012 [May 13th, 2012]
- Two Molecular Biologists Get $500K Medical Prize - May 13th, 2012 [May 13th, 2012]
- Pair of molecular biologists receive Albany Medical Center Prize - May 13th, 2012 [May 13th, 2012]
- CNIO scientists successfully test the first gene therapy against aging-associated decline - May 16th, 2012 [May 16th, 2012]
- Cancer Institute of New Jersey Aims to Advance Personalized Cancer Treatments Through 'Precision Medicine' - May 16th, 2012 [May 16th, 2012]