Mutated DNA Fixed in Patients: A Huge Step for Gene Therapy

A recent article by Gina Kolata, published on March 10, 2025 in The New York Times, discusses an exciting breakthrough in gene therapy. Scientists have succesfully fixed a genetic mutation with a single infusion carrying a treatment that precisely targets the mutated gene. This is for the first time that a mutated gene has been returned to normal. This study led by Beam Therapeauticals, focused on alpha-1 antitrypsin deficiency (AATD), which is a genetic disorder that causes serious lung and liver damage and instead of using traditional gene therapy which involve adding or silencing genes, scientists used a special version of CRISPR to edit a single DNA letter, like "correcting a typo" in the genetic code. The patients who received highest doses started making normal levels of the missing protein, which could mean stopping the disease before it gets worse.

        This coud be a turning point in gene therapy, proving fixing faulty DNA inside the body is possible and what's more interesting is that, according to Beam's CEO, John Evans there were no serious side effects. While researchers still have to study long term effects, if further trials confirms it's safety, this could save countless lives and maybe it could pave the way for treating other genetic disorders like sickle cell anemia. The idea of editing DNA, like fixing a typo is something that holds the potential to save many people suffering from genetic disorders.

New Study Reveals Shared Genetic Markers Underlying Substance Use Disorders

 

     Scientists have identified genes that are commonly inherited across addiction disorders, regardless of what substance was used. The study was led by researchers at the Washington University in St. Louis. In 2021, more than 46 million people in the U.S., at the age of 12 or older, had at least one substance use disorder, with only 6.3% receiving treatment. About 107,000 people died of drug overdoses in 2021, with 37% of the deaths involving opioid and stimulant drug exposure. Disorders caused by substance use are heritable and influenced by interactions among different genes and environmental factors. The genome-wide association is a method that searches entire genomes for regions of genetic variation, called single-nucleotide polymorphisms, that associate with the same disease or condition among multiple people. In the study, researchers used this method to identify areas in the genome that were associated with general addiction risk and risk of substance specific disorders. A sample of 1,025,550 individuals with genes indicating European ancestry was used and so was a sample of 92,630 people with genes indicating African ancestry. The research team discovered various molecular patterns, including 19 independent SNPs associated with general addiction risk and 47 SNPs associated with substance specific disorders. These identified patterns were among the European ancestry. The strongest gene signals that were consistent across the different disorders were located in areas of the genome responsible for regulation of dopamine signaling, indicating that dopamine signaling regulation is an important part of addiction risk. The genomic pattern associated with general addiction risk predicted higher risk of mental and physical illness, including suicidal behaviors, chronic pain conditions, psychiatric disorders, and respiratory conditions. In children aged 9 to 10 years old, the presence of these genes correlated with parental substance use. Genomic analysis in the African ancestry sample showed one SNP associated with general addiction risk and one SNP associated with alcohol use disorder. 

This research is very intriguing. Firstly, it’s intriguing in that the results between the different ancestries are drastically different. It could also be taken into account the different sample sizes between the two ancestries. However, due to the sample sizes and the limited research done so far, the data cannot be used to categorize genetic risks within certain populations. But, including populations that have historically been underrepresented in biological and biomedical research could lead to a better accuracy in the found results. Hopefully, this research opens a pathway to discovering the factors that protect or predispose a person to a substance use disorder. Through these findings, the hope is that new treatments and preventative measures could be found against multiple substance use disorders

https://nida.nih.gov/news-events/news-releases/2023/03/new-nih-study-reveals-shared-genetic-markers-underlying-substance-use-disorders 

https://www.nimh.nih.gov/health/topics/substance-use-and-mental-health

Fruit Flies Help Reveal Effects of Autism-Linked Mutations

 

Experiments with fruit flies have allowed researchers to find and analyze rare genetic mutations that are commonly found in autistic individuals. By using fruit flies as ‘living test tubes’, researchers can study which genetic variants identified in autism spectrum disorder persons have functional consequences. The work focused on missense mutations, in which a switch of a single DNA letter alters one amino acid in a protein.

“The scientists engineered 79 autism-linked variants — most of which are missense variants — into the equivalent genes in fruit flies, or Drosophila. The variants came from the Simons Simplex Collection, a repository of genetic data from families with one autistic child. The researchers discovered that 30 of these changes had significant consequences for the flies, such as a reduction in courtship behaviors; greater or lesser amounts of grooming; smaller eyes; and smaller, crumpled, serrated, blistered or absent wings” (Choi, 2022).

Scientists cautioned that although these 30 mutations did have strong consequences in fruit flies, they did not mean that they all had a direct correlation to autism in humans. One of the genes linked to disruptive effects in fruit flies is GLRA2. It helps control chemical messengers in the brain but if not present or found to be mutated shows as a spectrum of neurodevelopmental conditions, such as autism, epilepsy, developmental delay, and intellectual disability.

The strategy and testing method could help researchers investigate other human mutations of unknown significance and determine how genetics affect other diseases as well.

More research on autism and genetic studies can be accessed here. 

The Cause of Chewy Chicken Meat!

The Cause of Chewy Chicken Meat!

Almost everyone eats chickens, and ever wonder why some chicken meat is soft and some hard and chewy? Recently published, the University of Delaware researchers have discovered that lipoprotein lipase in chicken may contribute to wooden breast syndrome. Lipoprotein lipase is an enzyme that is important for fat metabolism. For decades, researchers have been studying wooden breast syndrome in broiler chickens that involved with analyzed genes in the disease and the identified biomarker for the disorder. The researchers also explain the hardened breast tissue from these chickens.

How did these researchers find that lipoprotein lipase is the answer? The researchers know that breast muscle fibers in chicken reply on sugar, which is a glucose molecule for fuel and not fat molecules in this case. They use RNA sequencing to determine which genes expressed, and finally, they found evidence of lipoprotein lipase expressed in endothelial cells. Since fat oxidized for energy in the breast, it causes another excess release of the free radical molecule that modifies the terrible fats and protein, which then causes a problem for the chicken’s immune system. This eventually leads to hard and chewy chickens.


This is a useful finding that researchers were able to discover. This would help growers manage to be more cautious about what they feed or look over how the conditions of the chicken are before actually going into the market, processed for meat, or breeds that may result in economic losses or disease spreading.


https://www.sciencedaily.com/releases/2019/11/191120175613.htm
https://eurekalert.org/pub_releases/2019-11/uod-tco112019.php

Genes Linked to Schizophrenia?

 Schizophrenia is a long-term mental disorder that involves a breakdown between emotion, behavior, and thought. This disorder tends to run in families and is mostly inherited. Researchers began to gather patients’ exomes for 24,000 people with schizophrenia and about 97,000 people without schizophrenia. Ten genes believe in finding that promote schizophrenia. GRIN2A, SP4 overlap with GWAS markers suggests high-risk mutations that boost schizophrenia risk. GRIN2A and GRIA3 encode for brain receptors for the neurotransmitter glutamate also suggest high-risk mutations as well. Scientists also suggest that the glutamate pathway is also the factor of schizophrenia due to how PCP and ketamine receptors blocked can boost the high risk of schizophrenia symptoms. Since scientists believe there might be something involved with the glutamate pathway, many are experiencing how to develop drugs that can prevent the receptors from being block.

Picture from Verywell Mind

This is good to know that there is hope of finding treatments to help treat symptoms of schizophrenia or maybe to prevent it. Since schizophrenia is hereditary, genetics is just one possible factor risk that may be inherited and pass down to family. Scientists already found ten genes that likely promote schizophrenia, and by finding ways to revert these genes, the risks of developing schizophrenia will decrease?

https://www.sciencemag.org/news/2019/10/intensive-dna-search-yields-10-genes-tied-directly-schizophrenia

https://www.news-medical.net/news/20191024/Gene-linked-to-schizophrenia-likely-confers-risk-for-illness.aspx

Sickle-cell Disease Cure May Be on the Horizon

An article from The New York Times discusses that success may have been made in "the first genetic cure of a common genetic disease". Sickle-cell disease affects the blood. It causes red blood cells to have a sickle or crescent shape as opposed to normal cells with a more smooth and circular shape. (NIH) The sickle shape of the cell causes issues with the ability of the cell to move through the circulatory system. It typically affects individuals of African descent. There is one specific gene that causes sickle-cell disease. It was believed that the disease could be cured if they could fix the problem on a genetic level. Stem cells are taken from a patient's bone marrow and then they are genetically modified and put back in to the individuals bloodstream, with hopes that they will form new and healthy blood cells.

I know that sickle-cell disease can be very painful and dangerous. The young man in the article that received the gene therapy treatment had suffered from four strokes by the time he was 18. Many people also die from complications of this disease. The fact that we are capable of making changes to someone on a genetic level is incredible. This could be a huge stepping stone in treatment for many other genetic disorders.

Fatal Familial Insomnia

Genes provide instructions for creating proteins that play a critical role in many functions of the body. When a mutation of a gene occurs, the protein product may be faulty, inefficient, absent, or overproduced. Depending upon the functions of the particular protein, this can affect many organ systems of the body, including the brain.

The disease is linked to be found in the PRNP gene, which produces a protein called prion protein, or PrP. In FFI the variant gene, the PrP that is produced develops an abnormal 3-dimensional shape that is described as misfolded. This is toxic to the body, especially to cells of the nervous system. In FFI, misfolded PrP is primarily found in the thalamus, which is a structure deep within the brain that helps to regulate many functions of the body including sleep, appetite, and body temperature. As the misfolded PrP builds up in the thalamus, it results in a progressive destruction of nerve cells (neurons), which leads to the symptoms of the disorder.

FFI is classified as a transmissible spongiform encephalopathy (TSE) or a prion disease. Prion diseases are caused by the accumulation of misfolded prion proteins in the brain. This disorder is very rare, and it degenerates the brain. The characteristic symptom in FFI is progressive insomnia. Some people may start having insomnia suddenly and from being mild it then becomes progressively worse until an affected individual gets very little sleep. The lack of sleep leads to physical and mental deterioration and the disease ultimately progresses to coma and death.

This disease can be a product of two unaffected parents and in rare instances, a variation in the PRPN gene in individuals with FFI occurs spontaneously, without a family history of the disease. However, a person that is affected with this disease could pass on the variant gene to their offspring in an autosomal dominant manner. Unfortunately, there is no cure for this disease, but researchers are finding a way to help treat the disease.

Sources

https://rarediseases.org/rare-diseases/fatal-familial-insomnia/ Fatal Familial Insomnia

https://ghr.nlm.nih.gov/gene/PRNP PRNP gene

prion protein

The Truth on Online Gene Testing.

A 29-year-old radiology resident at Baylor University Medical Center, Dr. Joshua Clayton sent in a sample of his saliva to 23andMe in hopes of learning more about his ancestry. 23andMe is one genetics testing company out of many where people can send in DNA samples and get quick results for a decent price. However, many physicians are arguing that is may be doing more harm than good. After Dr. Clayton’s results came back ordinary, he sent the same sample of DNA to a separate genetics testing company called Promethease which advertises to do a more in-depth analysis. The results of the analysis came back positive for Lynch syndrome, a genetic disorder that can lead to deadly cancers at an early age. Frightened by this, Dr. Clayton reached out to a company with expertise in medical diagnostics and found that the  results from Promethease were actually a false positive. Although he knew false positives were common in these genetic testings, many consumers do not understand how debatable their results may be. In a small study performed by Ambry Genetics, it was found that 40% of the results from these companies were erroneous. These testing companies do state that their results are not intended for medical purposes yet this can be very confusing when the consumer is expecting to have accurate results.

Personally, I do not see the harm in participating in these genetic testing activities, however, one should never rely solely on the validity of the results. If there is a chance a mutation is hereditary than one should be examined by a certified clinical laboratory. Possibly having a genetic disorder is worrisome enough so why take the chance of being misdiagnosed.

Related article

Reference Article

Gene Therapy Creates Replacement Skin to Save a Dying Boy

Specialists in Europe utilized quality treatment to develop sheets of solid skin that spared the life of a kid with a hereditary sickness that had devastated a large portion of his skin.

This was not the principal utilization of the treatment, which adds quality treatment to a procedure created to develop skin unites for consume casualties. In any case, it was by a long shot the most body surface at any point canvassed in a patient with a hereditary issue: nine square feet.

The kid's illness, junctional epidermolysis bullosa, causes to a great degree delicate skin that rankles and tears, and is inclined to contaminations and skin tumor. He had been required to kick the bucket however has recuperated. Two years after the treatment, he keeps on having sound skin and have an ordinary existence. A video gave by the restorative group demonstrates the kid, Hassan, playing soccer with his dad. As indicated by news reports, the family is initially from Syria.

Epidermolysis bullosa takes different structures, contingent upon the hereditary transformation included. Around 25,000 individuals in the United States have the condition, and 500,000 around the world. The seriousness changes, however a few patients spend a lot of their lives canvassed in gauzes and in extreme agony.

Brett Kopelan, who has a kid with the ailment and is official executive of a help and support gathering, Debra, said that the profoundly specific dressings his girl needs cost more than $500,000 a year.

Click Link 1 and Link 2 to read the amazing articles and how this boy's life was saved!

Insomnia has been linked to several genes

Insomnia is a disorder than many of us have had to go through at some point in our lives. But only 10% of the entire country has been reported to have chronic insomnia. A group of researchers found seven different genes that coded for insomnia, proving it is a genetic disorder that is fairly common. The researchers also found that the genes that code for insomnia also link to many other genetics disorders such as, restless leg syndrome, anxiety, depression, and neuroticism. This article was interesting to read because it has always been known that disorders like anxiety and depression were commonly associated with insomnia. Not everyone has been affected by insomnia directly but almost everyone has known someone who suffered from insomnia.

https://www.medicalnewstoday.com/articles/317919.php?sr
https://sleepfoundation.org/insomnia/content/what-causes-insomnia

Genetic Catastrophe in a Polygamous Town

Within the heavy mormon population of Utah, there is a high occurrence of genetic disorders popping up. An article by the BBC states that this has a lot to do with the high occurrence of polygamy within the Mormon community. Recessive genes seem to pop up quite frequently, some of the most common being facial features such as a prominent forehead, low-set ears, widely spaced eyes and a small jaw. They also have cognitive and development issues resulting from the small dating pool within the community. The Utah Cancer Regency said they also are at higher risk of certain cancers that have a strong genetic component. Ironically, though, they tend to live longer due to the community's strict policies against smoking and drinking. For more information about the mormon community visit a related link: http://archive.sltrib.com/story.php?ref=/utah/ci_3498536 

Possible Treatment for Cystic Fibrosis Discovered



Cystic fibrosis is an inherited life-threatening disease that damages the respiratory and digestive systems in the body. This disease affects 30,000 people in the US alone and currently has no cure however, recent research shows that a certain therapeutic approach may stop the disease from progressing.  Secretory glands in the body are responsible for the production  of mucus and swear, in a person with CF however, these secretions build up in the lungs causing respiratory infections as well as cause other infections in other parts of the body affected.

A group of researchers from George Washington University as well as the University of Perugia and the University of Rome have identified a synthetic polypeptide called thymosin alpha 1 and have examined its therapeutic affects. Thymosin alpha 1 is a synthetic form of a polypeptide found in thymus tissue. A mutation in the genetic code of a protein called cystic fibrosis transmembrane conductance regulator (CFTR) causes CF. The mutation causes the protein to degrade prematurely which leads to poor chloride permeability in the affected areas and causes inflammation and infection. With the combination of several drugs, a therapeutic approach is able to be made that has shown multiple beneficial effects, more then ever found when dealing with the cure for CF. I believe this is a huge step in the right direction for curing this disease that so many people in the world are diagnosed with. Hopefully with further funding and more extensive research done, a complete cure can be made to totally eradicate this disease and save the lives of tens of thousands of people.

Links:
http://www.medicalnewstoday.com/articles/316837.php
https://gidigest.musc.edu/potential-new-treatment-for-cystic-fibrosis-uncovered-medical-news-today/

Facial-recognition software finds a new use: diagnosing genetic disorders

Inspired by observations made by Dr. Maximilian Muenke, it has been hypothesized that distinctive facial features may indicate the presence of a genetic disorder within an individual. He claims from his experience within the field, it is exceptionally easy for him to look at a patient and diagnose an existing condition such as William's syndrome, without any prior pedigree knowledge or medical testing. Although this immediate recognition may not always be completely accurate, it could give reason for someone to seek genetic testing or counseling if necessary. This skill is to be applied in the facial-recognition technology that is readily available today. Scientists hypothesize this technological breakthrough could be especially useful in instances where genetic testing is not available, and people who wish to have accurate medical help, or do not wish to pass such genetic disorders onto their children. Even in advanced societies, individuals with such syndromes could be misdiagnosed, and this will aid physicians in finding the best treatment for their patients. Face2Gene is a new program developed by FDNA, a Boston based start up, which is readily available to clinicians as a mobile app in which they may take photographs of their patients, with their consent, to be analyzed for possible syndromes they may have. A now quickly moving force, this new technology will have to be constantly updated and improved with the help of both developers and geneticists to keep the possible diagnoses as accurate and as useful to the public as possible. I believe if this technology is used properly, and can be as accurate as it claims, Face2Gene could really give clinicians, genetic counselors, and the public an edge on making actions to both treat and prevent deleterious and unwanted genetic syndromes. I hope this application is used as it is intended, and can genuinely make a difference in our society in dealing with these conditions.

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