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Tag: Huntington’s Disease

Huntington’s Unveiled: Delving into Delayed Onset and the Fun Side of Therapeutic Possibilities

Greetings, health explorers! Today, we embark on a riveting exploration into Huntington’s disease, where scientists, spearheaded by the brilliant geneticist Bob Handsaker, have unveiled a compelling clue about its delayed onset in this article

Picture this: Huntington’s disease stems from a mistakenly repeated segment in the HTT gene. Bucking the conventional belief that these repeats remain constant, the research illuminates their dynamic growth in specific brain cells over time. As these repeats breach a critical threshold, the very activity of numerous genes in the affected brain cells undergoes a dramatic transformation, ultimately leading to cell death. The tantalizing prospect arises – could preventing the expansion of these repeats be the key to halting the development of Huntington’s disease?

 But fear not! The study hints at a potential game-changer – curbing the expansion of these repeats might be the key to slamming the brakes on Huntington’s disease development.

HuntingtonLet’s summarize what the article’s main idea was. Scientists, led by geneticist Bob Handsaker, have uncovered a significant clue about the delayed onset of Huntington’s disease. The disease arises from a mistakenly repeated segment in the HTT gene. Contrary to the belief that these repeats remain constant, the research reveals their dynamic growth in specific brain cells over time. Once the repeats surpass a critical point, the activity of numerous genes in the affected brain cells changes drastically, leading to cell death. The study suggests that preventing the expansion of these repeats may offer a way to halt the development of Huntington’s disease.

But let’s not stop there – delve deeper into the intricacies.

Before we move on, let’s pause. Do you know what Huntington’s disease is? Before you move on, read this brief article on Huntington’s disease.  

Anyway, let’s continue! A study on the neurological manifestations of Huntington’s disease beckons us, offering insights into the broader impact on the brain. The article, GENETICS AND NEUROPATHOLOGY OF Huntington’s DISEASE, reveals a breakthrough in understanding Huntington’s disease, shedding light on why the fatal brain disorder takes a prolonged time to manifest and suggesting a potential strategy to halt its progression. The key finding is that in some brain cells, the repeats of a gene called HTT, responsible for Huntington’s disease, can grow to hundreds of copies over time. When the number of repeats surpasses a certain threshold, the activity of thousands of other genes in the brain cells changes drastically, leading to cell death.

ADAR Protein

This discovery is connected to this article   about CRISPR technology and its use in treating genetic disorders. The link lies in the common theme of genetic manipulation and its potential role in addressing hereditary diseases. In the case of Huntington’s disease, the research suggests that preventing the expansion of repeats in the HTT gene could stop the development of the disease. This aligns with the broader theme of genetic interventions discussed in the CRISPR article.

Moreover, the article highlights the role of MSH3, a protein involved in DNA repair, in inadvertently adding CAG sequences to the HTT gene. Lowering the levels of this protein may prevent the expansion of repeats. This mechanistic insight provides a potential target for therapeutic intervention, indicating a different approach from current strategies that focus on lowering levels of the huntingtin protein.

In AP Biology class, we covered cell signaling, where cells communicate through molecular signals to regulate various processes. Signaling pathways involve receptors, intracellular messengers, and cellular responses. The Huntington’s disease article reveals that the expansion of CAG repeats in the HTT gene leads to changes in the activity of thousands of genes in brain cells. This alteration in gene activity can be seen as a response to an abnormal signal, impacting cell function. Understanding how abnormal signals lead to cellular dysfunction is crucial to cell communication.

In conclusion, Handsaker’s research cracks the molecular intricacies of Huntington’s disease, providing a deeper understanding of its development and offering potential therapeutic routes. The connection to AP Biology principles underscores the relevance of this study in the broader context of cellular communication and genetic signaling. What are your views on this paradigm shift in Huntington’s research? How might targeting DNA instability revolutionize therapeutic strategies? Please share your thoughts, and let’s engage in a meaningful discussion on this fascinating topic.


CRISPR May Be the Cure!

There are still many disorders and diseases in this world that cannot be cured, and Huntington’s disease (HD) is one of them.

HD is a neurological disorder that causes individuals to lose control of movement, coordination, and cognitive function. HD occurs because of a mutation in the Huntingtin (HTT) gene where a specific codon sequence repeats, creating a long, repetitive sequence that turns into a toxic, expanded protein clump. These clumps form in a part of the brain that regulates movement called the striatum and prevent the neurons in the striatum from functioning properly. As of now, HD still has no cure, but CRISPR gene editing (Clustered Regularly Interspaced Short Palindromic Repeats) might just be the solution.

Dr. Gene Yeo of UC San Diego School of Medicine, along with his team and colleagues from UC Irvine and Johns Hopkins University, researched RNA-targeting CRISPR/Cas13d technology as a way to possibly eliminate HD and its negative effects on the brain. CRISPR gene editing, as its name suggests, enables scientists to “edit” – add, remove, or alter – existing genetic material. The group desired to see if RNA-targeting CRISPR would be able to prevent the creation of the protein clumps that damage the function of the striatum. As we learned in AP Biology, the addition, removal, or substitution of a base of a codon can drastically change the structure and function of a protein. Each codon codes for a specific amino acid, and if multiple codons have changed due to a mutation, it is likely that the protein will fold differently than it is supposed to and will lose its function.

Yeo and his team desired to develop an effective therapy for HD, hoping to stop the formation of toxic protein clumps and alter the course of the disease. However, they did not want to create permanent changes in the human genome as a precaution. The team instead engineered a therapy that alters the RNA that turns into the protein clumps.  They conducted testing on mice and found that RNA-targeting CRISPR therapy reduced toxic protein levels in a mouse with HD, improving motor coordination. In connection with the molecular genetics unit in AP Biology, since the RNA that causes HD is altered, the protein that is translated will change since different amino acids correspond to different codons.

Transcription and Translation

Further testing will be necessary to confirm the benefits of this therapeutic strategy, but CRISPR does look like a promising medical treatment for HD and many other diseases in the future.

Progress in Treating Huntington’s Disease Thanks to CRISPR Technology

Scientists have discovered a new way to treat Huntington’s disease, thanks to CRISPR technology. Their research has reduced symptoms of the disease in the mice that they tested on. 

Huntington’s Disease, which is a neurological disorder, is caused by a genetic mutation in the HTT gene. More specifically, repetitive and damaging sequences in the HTT gene cause Huntington’s disease. It causes progressive loss of movement, coordination, and cognitive functions. 

Researchers have discovered a possible solution to these symptoms: CRISPR technology. 

According to the article, “CRISPR is a genome-editing tool that allows scientists to add, remove or alter genetic material at specific locations in the genome.” One of the risks of CRISPR use is that it can affect off-target genes and molecules, causing unwanted alterations in chromosomes and genes. 


Study author Gene Yeo, PhD, explains how our cells struggle to copy repetitive DNA, which can lead to errors that cause repetitive sequences to increase with each generation. As we learned in class, the process to copy DNA is a complex one where there are many factors at play. DNA is replicated in a semi conservative manner, meaning that the old DNA strands are conserved and combined with the new, complementary strands. There is a replication fork, with a leading and lagging strand, on which DNA is replicated in the 5’-3’ direction. For replication on the leading strand, RNA primase adds RNA, DNA polymerase III adds nucleotides to the open end of the RNA, then a sliding clamp attaches to the DNA polymerase III and slides it along the strand, resulting in the leading strand being synthesized. 

The scientists directly targeted the RNA involved in the DNA replication process to remove toxic protein buildup that is responsible for the mutation in the HTT genes. They were able to complete this process using CRISPR, and without disrupting other important genes. 

After testing on mice, they reported that their research has resulted in improved motor coordination, less striatal degradation and reduced toxic protein levels. These improvements on the mice’s condition lasted for up to 8 months, and had no on other RNA molecules, making scientists optimistic that this treatment could be effective for humans. 

A Potential Cure: We’ve Waited 151 Years For This!

CRISPR-Cas9 Editing of the Genome (26453307604)


CRISPR, which stands for Clustered Regularly Interspaced Short Palindromic Repeats, is a gene editing tool comprised of DNA sequences from prokaryotes, that is becoming more commonly used to treat and potentially cure life-threatening diseases that have previously been viewed as a death sentence; in December of 2022, a study was conducted at the University of California San Diego School of Medicine, where it was discovered that CRISPR technology can be used to target the gene that causes Huntington’s Disease.


First, we must understand what exactly Huntington’s Disease is. Huntington’s Disease, which was discovered in 1872, is a rare neurological disorder characterized by the gradual destruction of nerve cells in the brain. It is caused by a single defective gene, and this mutation is as dangerous and tragic as it is rare; the disease has no cure, and patients typically do not survive beyond 20 years post-diagnosis. 


However, thanks to CRISPR, it is a very real possibility that that will soon change. 


The study that was conducted at U.C. San Diego involved the experimentation of Cas13d – an RNA editing technique – against toxic RNA and protein buildup that is associated with the HTT gene mutation that causes Huntington’s Disease, and the trial was found to be successful in terms of eliminating that buildup. The experiment was conducted on mice, and it was also discovered that only one injection of the Cas13d therapy was necessary to yield results, and the benefits (improved motor function, lessened symptoms) lasted for eight months.


This discovery is especially fascinating as it connects to our AP Biology units in terms of mutations: The most common genetic mutations are insertions, substitutions, and deletions. The mutation that causes Huntington’s Disease, however, fits into neither one of these categories: if anything, the mutation is considered a duplication, as it is characterized by the unwanted repetition of cytosine, adenine, and guanine; these repetitions are what lead to the protein buildup, and damage the HHT gene. 


In previous years leading up to the U.C. San Diego experiment, trials conducted to target the gene that causes Huntington’s Disease have mostly been unsuccessful, but we can hope that this new discovery is a step in the right direction and may provide the key to figuring out how to treat this disorder that has historically been viewed as a death sentence.

CRISPR technology may be the key to treating Huntington’s Disease

Huntington’s disease is a well-known neurological disorder that is characterized by a loss of movement, coordination, and cognitive function. More than 200,000 people live with Huntington’s disease and more than a quarter million Americans are at risk of inheriting the diseases, but there is currently no cure. Scientists have recently been trying to develop a treatment using RNA-targeting CRISPR/Cas13d technology to eliminate toxic RNA that causes Huntington’s disease. CRISPR allows scientists to edit, add, and remove genetic material from specific places in the genome. This tool is based on a immune-defense mechanism from bacteria. Since there is a risk of editing a part of the genome unintentionally, studies have focused more on targeting RNA directly instead.

Huntington’s disease is caused by a mutation in a gene for the protein huntingtin. This mutation, known as a trinucleotide repeat expansion, causes cytosine, adenine, and guanine to be repeated many more times in the gene that normal. As a result, the protein that is produced can form toxic clumps in the part of the brain responsible for movement, which is called the striatum.

In AP Bio, we learned how genes are used to produce proteins that our bodies use. First, the RNA polymerase creates mRNA from transcribing DNA. A guanine nucleotide is added to the 5′ end, a poly-A tail is added to the 3′ end, and the introns are cut out. Then, the mRNA leaves the nucleus and goes to a ribosome for translation. The anticodon on the tRNA matches with the codon on the mRNA, which brings along the corresponding amino acid. The amino acid connects with the next amino acid to create a protein molecule. The additional CAG sequences in the huntingtin gene are transcribed onto the mRNA, which is then used to create a polypeptide. Since it is longer than normal, this protein’s shape will be deformed and will be toxic to the brain.

In neuronal cultures from patients with Huntington’s disease, scientists have used CRISPR to destroy mutant RNA molecules and clear out toxic protein buildup. Other genes were not affected by this treatment. When tested in mice, scientists found that the mice had better motor coordination and less toxic protein levels.CRISPR CAS9 technology

I chose this topic because I am very interested in how scientists can use mechanisms seen in other organisms to help treat human diseases.


CRISPR Provides New Hope for those with Huntington’s Disease


Neuron with mHtt inclusion

Neurons transfected with a disease-associated version of huntingtin

Huntington’s disease is a neurological disorder that affects the basal ganglia and cerebral cortex of the brain. These areas of the brain are associated with movement, learning, thinking, planning, motivation, and emotion. Huntington’s disease is caused by a single mutation in the huntingtin (HTT) gene, afflicting more than 200,000 people worldwide and 30,000 in the United States. There was believed to be no cure, however, novel research regarding CRISPR gene editing is giving those who suffer from this condition new hope. 

Identifying the problem (and connection to AP Bio)

“Our cells have a hard time copying repetitive DNA, and these copying errors can cause repetitive sequences to grow longer with each generation,” (Gene Yeo, PhD). 

Huntington’s disease is caused by repetitive and damaging sequences in the HTT gene. Within the cell cycle, in order for the cell to divide into two daughter cells during mitosis, the cell’s DNA must be replicated in the synthesis phase. In Huntington’s disease, the damage done to the HTT gene is carried through the synthesis phase, causing everlasting effects on future generations of cells. These repeated genes amass to many times their normal length and result in toxic clumps which aggravate the striatum of the brain which is important in regulating movement; thereby leading to Huntington’s Disease. 

Inventing a solution

CRISPR is a tool that edits genomes by precisely cutting DNA and then letting natural DNA repair processes take over. The system consists of two parts: the Cas9 enzyme and a guide RNA. CRISPR illustration gif animation 1In this new study, Gene Yeo and his team of researchers at the University of California San Diego School of Medicine are using RNA-targeting CRISPR/Cas13d technology to develop a new therapeutic strategy that specifically eliminates toxic RNA that causes HD. Yeo delivered the CRISPR therapy through viral vehicles to neuronal cultures grown from the stem cells of an individual with Huntington’s syndrome. His team has found that the approach not only targeted and destroyed mutant RNA molecules but also cleared out toxic protein buildup without disrupting other genes. 

Predictions for the future

Black-mouse-in-purple-gloved-hands-2Yeo’s team collaborated with Wenzhen Duan’s team at Johns Hopkins to conduct preclinical testing in mice. They found that the CRISPR therapy improved motor coordination, attenuated striatal degradation and reduced toxic protein levels in a mouse model of HD. The therapy lasted for at least 8 months and caused minimal effects on other RNA molecules. Although a mice’s anatomy is nowhere near as complex as a human’s, this new research gives incredible insight into the future that CRISPR holds and how impactful its use can be.

Human skin cells reprogrammed directly into brain cells



Original article:

Some key words:

Neurodegenerative diseases: Disease such as Alzheimer’s, Parkinson’s and Huntington’s disease that undergo a neurodegenerative process, specific neurons are targeted for degeneration.

Spiny brain cell: The desired end brain cell in this study, and a brain cell affected by Huntington’s disease


In a study by the researchers at Washington University School of Medicine in Saint Louis, they demonstrate a way for human skin cells to be specifically converted to a type of brain cell. This study can help in the rehabilitation of people with Huntington’s disease by turning skin cells in to brain cells that are lost through this neurodegenerative disease. This is all accomplished without passing through the stem cell phase preventing other cell types forming.

This research involved adult skin cells that Yoo, the senior author, and his colleagues reprogrammed by using two microRNAs: miR-9, and miR-124. These micro RNAs open up the otherwise tightly packaged and inactive sections of the gene critical to the formation of brain cells. While the micro RNAs open up genes used for the creation and functionality of neurons, transcription factors taken from a part of the brain where medium spiny neurons are common directs the newly formed brain cells to a specific subunit of brain cells. The researchers then observed that the newly formed brain cells behave and function in a similar way to the native medium spiny neurons in mice, allowing this study to proceed in to further stages of experimentation, and hopefully result in a treatment practical for human use.

This study is very critical in the advancement of the treatment for neurodegenerative disease such as Huntington’s disease. Using different transcription factors from parts of the brain, alternate types of brain cells can be created to replace cells lost from neurodegenerative effects. This form of treatment will also prevent rejection of the transplant because the skin cells can be taken from the patient’s own body. This is a breakthrough in our pursuit of cures for these lethal neurodegenerative diseases.

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