Treating Cystic Fibrosis during pregnancy Before Birth with Trikafta

Very recommendable!

(252) CF Before Birth: The Battle Against Cystic Fibrosis | NOVA | PBS - YouTube

Could Genetic Therapies Finally Cure Cystic Fibrosis?

Good news! Only a few years away from application!

(239) Could Genetic Therapies Finally Cure Cystic Fibrosis? | NOVA | PBS - YouTube

Groundbreaking study reveals hidden complexity in human genetics

Amazing stuff!

Unfortunately, this article lacks a reference to the research paper! Using Google Scholar, I was not able to find this paper!

"... the key was to account for variant combinations in a gene, also called epistasis. They measured functional effects of variant combinations in the DNA of a key enzyme, argininosuccinate lyase (ASL), a lack of which results in urea cycle disorder, a rare but devastating condition.  

The researchers tested thousands of variant combinations that resulted in no enzyme activity when on their own and found that a significant portion of them had high levels of enzyme activity when in combination with each other. In other words, two defective variants, when combined, can recover function. ...

[Francis] Crick, who shared the Nobel Prize in Physiology or Medicine 1962 with James Dewey Watson and Maurice Wilkins for their discoveries concerning the molecular structure of DNA, had hypothesized this could happen.

“Crick had a fancy word for it—variant sequestration,” ... “But until [now], no one had demonstrated it.” ..."

Groundbreaking study reveals hidden complexity in human genetics | George Mason University "Sometimes, in genetics, two wrongs do make a right. A research team recently showed that two harmful genetic variants, when occurring together in a gene, can restore function—proving a decades-old hypothesis originally proposed by Nobel laureate Francis Crick. Their study ... not only experimentally validated this theory but also introduced a powerful artificial intelligence (AI)-driven approach to genetic interpretation ..."

8 healthy babies born after scientists use DNA from 3 people to avoid genetic disease

Good news

The durable cure for cystic fibrosis might start in the womb

Good news!

"... Using in utero gene editing, the researchers developed a method to deliver corrective genetic material to the fetus of mice with CF via tiny particles called nanoparticles. ...

Cystic fibrosis arises from mutations in the CF transmembrane conductance regulator, or CFTR. Because the disease is caused by a single mutation, researchers saw it as a great candidate for gene editing, specifically in utero gene editing.  ...

In the study, researchers used synthetic molecules similar to DNA — called peptide nucleic acids, or PNAs — to correct CFTR. PNA can be tweaked to bind to a particular gene containing a mutation in a strand of DNA, which can cause a lesion that the cell then removes itself. The gene is then corrected when a strand of DNA without the mutation takes its place. ...

The researchers delivered the PNA to the fetuses of mice using tiny synthetic particles called nanoparticles, which are the same size as viruses to correct the CFTR mutation before the mice were born. ..."

From the significance and abstract:

"Significance

Cystic fibrosis (CF), a monogenic disease resulting from mutations in the CF transmembrane conductance regulator (CFTR) gene, affects multiple organs, including the respiratory, gastrointestinal, and reproductive systems.

Irreversible pathology in these tissues is often already present at birth, suggesting that a true curative therapy would require intervention during fetal development.

Here, we demonstrate CFTR gene correction in multiple tissues affected by CF after a single in utero administration of nanoparticles containing gene editing cargo. We found that gene correction was durable into adulthood in mice, which resulted in functional CFTR activity in both the respiratory and gastrointestinal systems. Our work establishes the possibility that CF could be treated, or possibly cured, by a single in utero gene editing treatment.

Abstract

In utero gene editing has the potential to modify disease-causing genes in multiple developing tissues before birth, possibly allowing for normal organ development, disease improvement, and conceivably, cure. 

In cystic fibrosis (CF), a disease that arises from mutations in the CF transmembrane conductance regulator (CFTR) gene, there are signs of multiorgan disease affecting the function of the respiratory, gastrointestinal, and reproductive systems already present at birth. 

Thus, treating CF patients early is crucial for preventing or delaying irreversible organ damage. Here, we demonstrate proof-of-concept of multiorgan mutation correction in CF using peptide nucleic acids encapsulated in polymeric nanoparticles and delivered systemically in utero.

In utero editing was associated with sustained postnatal CFTR activity, at a level similar to that of wild-type mice, in both respiratory and gastrointestinal tissues, without detection of off-target mutations in partially homologous loci. This work suggests that systemic in utero gene editing represents a viable strategy for treating monogenic diseases before birth that impact multiple tissue types."

The cure for cystic fibrosis might start in the womb | Yale News "In a new study, Yale researchers develop a method that has the potential to cure cystic fibrosis prior to birth."

Systemic in utero gene editing as a treatment for cystic fibrosis (no public access)

Marie Egan, a senior author of the study

Researchers identify almost 300 genetic disorders that can be treated before birth

Good news!

Again it is disgusting and annoying how Harvard U avoided to say "woman" for most likely ideological reasons! Women are either "pregnancies" or "patients" or "families" or "individuals".

"A new study identifies nearly 300 genetic disorders that can be treated during pregnancy or in the first week of life, forming the basis for a “treatable fetal findings list” that could be offered to pregnant patients.

The findings could improve the diagnosis of genetic conditions in pregnancy and enhance the treatment options available for fetuses that have these conditions ...

Over the past decade, genomic sequencing has become a vital tool to help inform prenatal diagnoses. Genomic sequencing tests, combined with family history, can help identify genes responsible for ultrasound abnormalities. They can also uncover incidental findings that may predispose a fetus or newborn to serious but treatable conditions, such as a heart condition that can be treated with medications or a gastrointestinal disorder that can be managed with fluid and electrolyte therapies. ...

Through a literature review, the authors identified a total of 296 genetic conditions, ranging from disorders with emerging fetal therapies to those where immediate postnatal treatment can prevent irreversible harm. The authors emphasize that timely detection of these conditions could reduce morbidity and mortality, offering families unprecedented opportunities for early intervention. ..."

From the abstract:

"The use of genomic sequencing (GS) for prenatal diagnosis of fetuses with sonographic abnormalities has grown tremendously over the past decade.

Fetal GS also offers an opportunity to identify incidental genomic variants that are unrelated to the fetal phenotype but may be relevant to fetal and newborn health. There are currently no guidelines for reporting incidental findings from fetal GS.

In the United States, GS for adults and children is recommended to include a list of “secondary findings” genes (ACMG SF v.3.2) that are associated with disorders for which surveillance or treatment can reduce morbidity and mortality. The genes on ACMG SF v.3.2 predominantly cause adult-onset disorders.

Importantly, many genetic disorders with fetal and infantile onset are treatable as well.

A proposed solution is to create a “treatable fetal findings list,” which can be offered to pregnant individuals undergoing fetal GS or, eventually, as a standalone cell-free fetal DNA screening test.

In this integrative review, we propose criteria for a treatable fetal findings list, then identify genetic disorders with clinically available or emerging fetal interventions and those for which clinical detection and intervention in the first week of life might lead to improved outcomes. Finally, we synthesize the potential benefits, limitations, and risks of a treatable fetal findings list."

Researchers ID genetic disorders that can be treated before birth — Harvard Gazette "Timely detection could reduce morbidity, offers opportunities for early intervention"

Advancing precision care in pregnancy through a treatable fetal findings list (no public access)

Advancing precision care in pregnancy through an actionable fetal findings list (preprint, open access)

First in-womb gene treatment of a rare genetic disorder a success

Good news!

"A two-and-a-half-year-old girl shows no signs of a rare genetic disorder after becoming the first person to be treated for the motor-neuron condition while in the womb.

The child’s mother took the gene-targeting drug late in her pregnancy, and the child continues to take it. The drug, risdiplam, modifies the expression of a gene called SMN2 to produce more of a protein required for maintaining motor neurons in the spinal cord and brainstem."

"... "The “baby has been effectively treated, with no manifestations of the condition”, ...

The child was conceived with a genetic condition known as spinal muscular atrophy, which affects motor neurons that control movement, and leads to progressive muscle weakening. About one in every 10,000 births have some form of the condition — making it a leading genetic cause of death in infants and children. ...

In the past decade, the US Food and Drug Administration (FDA) has approved three drugs to treat newborns for spinal muscular atrophy. The oral drug used in this study, called risdiplam, manufactured by biotech firm Roche, based in Basel, Switzerland, is a small molecule that works by modifying expression of the SMN2 gene so that it produces more SMN protein.

Up until now, treatments for spinal muscular atrophy were given after birth. But up to half of newborns lacking both copies of the SMN1 gene, and with only two copies of the SMN2 gene, are born with some symptoms. "

From the (extremely shor) abstract:

"The alternate splicing small molecule risdiplam, administered to a fetus with spinal muscular atrophy, had an apparent ameliorating effect on the disorder through 30 months."

Nature Briefing: Translational Research

Rare genetic disorder treated in womb for the first time "The child, who is now almost three years old, shows no signs of the often fatal motor neuron disease."

Risdiplam for Prenatal Therapy of Spinal Muscular Atrophy (no public access)

Babies with severe spinal muscular atrophy lack sufficient proteins to maintain motor neurons.

Genetics causes 1 in 4 cerebral palsy cases

Good news!

"A large Chinese study has re-affirmed growing evidence that genetics and not birth asphyxia is often responsible for cerebral palsy. ..."

From the abstract:

"Cerebral palsy (CP) is the most common motor disability in children. To ascertain the role of major genetic variants in the etiology of CP, we conducted exome sequencing on a large-scale cohort with clinical manifestations of CP. The study cohort comprised 505 girls and 1,073 boys. Utilizing the current gold standard in genetic diagnostics, 387 of these 1,578 children (24.5%) received genetic diagnoses. We identified 412 pathogenic and likely pathogenic (P/LP) variants across 219 genes associated with neurodevelopmental disorders, and 59 P/LP copy number variants. The genetic diagnostic rate of children with CP labeled at birth with perinatal asphyxia was higher than the rate in children without asphyxia (P = 0.0033). Also, 33 children with CP manifestations (8.5%, 33 of 387) had findings that were clinically actionable. These results highlight the need for early genetic testing in children with CP, especially those with risk factors like perinatal asphyxia, to enable evidence-based medical decision-making."

Genetics causes 1 in 4 cerebral palsy cases

Exome sequencing reveals genetic heterogeneity and clinically actionable findings in children with cerebral palsy (no public access)

Face Recognition for Genetic Disorders

Unfortunately, this technology appears not yet to be available to the general public!

"... People with certain genetic disorders share common facial features. Doctors are using computer vision to identify such syndromes in children so they can get early treatment. ...
Face2Gene is an app from Boston-based FDNA that recognizes genetic disorders from images of patients’ faces. Introduced in 2014, it was upgraded recently to identify over 1,000 syndromes (more than three times as many as the previous version) based on fewer examples. In addition, the upgrade can recognize additional conditions as photos of them are added to the company’s database — no retraining required. ..."

From the abstract:

"Syndromic genetic conditions, in aggregate, affect 8% of the population. Many syndromes have recognizable facial features that are highly informative to clinical geneticists. Recent studies show that facial analysis technologies measured up to the capabilities of expert clinicians in syndrome identification. However, these technologies identified only a few disease phenotypes, limiting their role in clinical settings, where hundreds of diagnoses must be considered. Here we present a facial image analysis framework, DeepGestalt, using computer vision and deep-learning algorithms, that quantifies similarities to hundreds of syndromes. DeepGestalt outperformed clinicians in three initial experiments, two with the goal of distinguishing subjects with a target syndrome from other syndromes, and one of separating different genetic subtypes in Noonan syndrome. On the final experiment reflecting a real clinical setting problem, DeepGestalt achieved 91% top-10 accuracy in identifying the correct syndrome on 502 different images. The model was trained on a dataset of over 17,000 images ... DeepGestalt potentially adds considerable value to phenotypic evaluations in clinical genetics, genetic testing, research and precision medicine."

P.S. Is this face or facial recognition? I suppose the latter.

The Batch: AI Without Coding, Face Recognition Sees Genetic Disorders, Simulating Stock Markets, Tracking AI's Global Progress

Identifying facial phenotypes of genetic disorders using deep learning (published 2019, no public access)