FDA clears first CRISPR treatment for a second disease, beta thalassemia
Source: CNN Health
Published 7:02 PM EST, Tue January 16, 2024
CNN — The US Food and Drug Administration has approved a second use for the first CRISPR-based medicine, Casgevy, which was approved in December to treat sickle cell disease.
The groundbreaking treatment can now also be used to treat transfusion-dependent beta thalassemia in people 12 and older. Like sickle cell, beta thalassemia is an inherited blood disorder. The FDA’s decision was expected, but it comes about two months earlier than the agency’s deadline for acting, called the PDUFA date.
To make Casgevy, a person’s stem cells are genetically modified using a precision gene editing technique called CRISPR/Cas9. The modified cells are then transplanted back into the body, where they grow and multiply and increase the production of hemoglobin, which decreases symptoms. The treatment lists for $2.2 million for both sickle cell disease and beta thalassemia.
“Today’s approval is an important step in the advancement of an additional treatment option for individuals with beta-thalassemia, a debilitating disease that places individuals at risk of many serious health problems,” said Dr. Nicole Verdun, director of the Office of Therapeutic Products within the FDA’s Center for Biologics Evaluation and Research, in a news release.
Using CRISPR, an immune system bacteria use to protect themselves from viruses, scientists have harnessed the power to edit genetic information within cells. In fact, the first CRISPR-based therapeutic was recently approved by the FDA to treat sickle cell disease in December 2023. That therapy is based on a highly studied system known as the CRISPR-Cas9 genetic scissor.
However, a newer and unique platform with the potential to make large-sized DNA removals, called Type I CRISPR or CRISPR-Cas3, waits in the wings for potential therapeutic use.
Groundbreaking gene therapy trial allows 5 children born deaf to hear
By Michael Irving
January 28, 2024
A breakthrough clinical trial using gene therapy has restored hearing to five children born deaf. After six months, the children were able to recognize speech and hold conversations, raising hopes for wider use in the near future.
The patients in the trial suffered from a genetic condition called autosomal recessive deafness 9 (DFNB9), which is caused by a mutation in a gene called OTOF. This gene produces the otoferlin protein, which helps transmit electrical pulses from the cochlea to the brain, where it can be interpreted as sound – but without it, those signals never get there. Because it’s caused by a single mutation, and doesn’t involve any physical damage to cells, the team says DFNB9 was the perfect candidate for this kind of gene therapy.
The gene therapy involves packaging the OTOF gene into viral carriers, and injecting the mix into the inner ear fluid. The viruses then sought out cells in the cochlea and inserted the gene into them, which allows them to start manufacturing the missing otoferlin protein and restore hearing.
A new discovery by Tel Aviv University has succeeded in cultivating and characterizing tomato varieties with higher water use efficiency without compromising yield. The researchers, employing CRISPR genetic editing technology, were able to grow tomatoes that consume less water while preserving yield, quality, and taste.
Scientists at the Francis Crick Institute have found a new treatment target for CDKL5 deficiency disorder (CDD), one of the most common types of genetic epilepsy.
CDD causes seizures and impaired development in children, and medications are limited to managing symptoms rather than tackling the root cause of the disease. The disorder involves losing the function of a gene producing the CDKL5 enzyme, which phosphorylates proteins, meaning it adds an extra phosphate molecule to alter their function.
Following recent research from the same lab showing that a calcium channel could be a target for therapy for CDD, the team has now identified a new way to potentially treat CDD by boosting another enzyme's activity to compensate for the loss of CDKL5.
In research published in Molecular Psychiatry, the scientists studied mice that don't make the CDKL5 enzyme. These mice show similar symptoms to people with CDD, such as impaired learning or social interaction.
Single-dose gene therapy may stop deadly brain disorders in their tracks
By Paul McClure
February 15, 2024
Researchers have developed a single-dose genetic therapy that can clear protein blockages that cause motor neurone disease, also called amyotrophic lateral sclerosis, and frontotemporal dementia, two incurable neurodegenerative diseases that eventually lead to death.
In healthy neurons, TAR DNA-binding protein 43 (TDP-43) is naturally produced and important for their healthy function. However, TDP-43 can be modified after synthesis, leading to its accumulation and aggregation in the wrong part of the cells, preventing them from working properly. These build-ups are associated with devastating neurodegenerative diseases like motor neurone disease (MND), also known as amyotrophic lateral sclerosis (ALS) or Lou Gehrig’s disease, and frontotemporal dementia (FTD).
Gene editing technology could revolutionize the treatment of genetic diseases, including those that affect the mitochondria—cell structures that generate the energy required for the proper functioning of living cells in all individuals. Abnormalities in the mitochondrial DNA (mtDNA) could lead to mitochondrial genetic diseases.
Targeted base editing of mammalian mtDNA is a powerful technology for modeling mitochondrial genetic diseases and developing potential therapies. Programmable deaminases, which consist of a custom DNA-binding protein and a nucleobase deaminase, enable precise mtDNA editing.
By silencing the gene responsible for regulating ‘bad’ cholesterol without altering the primary DNA sequence, researchers have shown that it’s possible to use epigenetic editing to treat diseases rather than conventional DNA-breaking gene editing technology, which risks unintended effects.
Because identical twins develop from a single fertilized egg, they have the same genome, the entire set of genetic material found in an organism. So, any differences between them, even in traits with a significant genetic component – say one develops heart disease and the other doesn’t – are due to their environments. This is known as epigenetics.
Genes in DNA are ‘expressed’ when they’re read and transcribed into RNA, which is then translated into proteins. It’s proteins that determine many of a cell’s characteristics and functions. Epigenetic changes can boost or silence the transcription of specific genes, ramping up or inhibiting associated protein production, but they don’t change the genome. These changes, which are reversible, can affect a person for their entire life and mediate a lifelong dialogue between genes and the environment.
