Deciphering My Myeloma Lab Results - HealthTree For AML

Huntington's Disease: The Genetic Brain Decay

The health landscape is already grappling with a slew of neurological disorders like cerebral palsy, dementia, Alzeimer's, Parkinson's and so on. The latest to haunt the brain and its nerve cells is Huntington's disease (HD). But what is it actually?

Decoding HD

HD is a neurological condition that affects the brain, inducing the neurons or nerve cells to decompose and get defunct over time. As a result, this adversely impacts mental health and vital cognitive skills like voluntary body movement, memory, thinking capacity, behavioural patterns and personality traits. "Well, to put it in simple terms, just imagine your brain to be a complex computer, and Huntington's disease a technical glitch that disrupts the way it works. It's a progressive disorder that can cause problems with movement, remembering and emotions, thus making everyday tasks a challenge," explains Dr Vinaya V. Bhandari, a consultant neurology and neuromuscular disorder specialist at Jaslok Hospital & Research Centre.

Dr Chirag Gupta, senior consultant neurologist, Fortis Greater Noida, depicts HD as "an inherited condition that causes brain cells to slowly lose function and die. It affects the cells in parts of your brain that regulate voluntary movement and memory."

All in the Genes

As Huntington's is widely described as a hereditary disease, Dr Bhandari suggests, "HD is like a genetic puzzle piece that can be passed down from parents to children." Talking us through the condition, she highlights the percentage that reflects the extent of transmission of the disease from parents to their offspring. "It's like flipping a fair coin probability. I mean each child of a parent with HD has a 50% chance of getting the mutated gene. While Huntington's can affect people of any age — be it children or adults — symptoms usually appear between 30 and 50 years," she informs.

Incidentally, HD affects an estimated 3 to 7 of every 100,000 people andis mostlyfound in descendants of European ancestry.

Palliative Care

People with impaired cognitive capabilities and clumsiness have to embrace a difficult lifestyle for survival. But some basic remedial measures can be taken during the treatment process of HD patients to control the problem and prevent it from deteriorating. "While there's no cure for HD, there are ways to manage symptoms and improve the overall quality of life. Medications, physical therapy, occupational therapy and speech therapy can help address this crisis. A healthy diet and regular exercise can also make a big difference," recommends Dr Bhandari.

Shift in Personality

Many patients even show signs of behavioural changes and altered personality attributes due to this neurological ailment. "HD can instigate drastic changes in behaviour, such as irritability, depression, obsessive compulsive disease, suicidal ideation and anxiety. Occurrence of these changes can be taxing for patients and frustrating for their loved ones, but with the right support and care, it's possible to manage such setbacks," assures the neurologist.

No Road to Recovery

Is it possible to heal Huntington's disease? Well, that's the million dollar question the medical community is racking its brain over to seek answers to. "Unfortunately, there's no antidote to beat HD or any corrective measure registered yet to counteract its harmful effects. However, researchers are working hard to find a solution to get rid of this malady," confirms Dr Bhandari.

Dr Gupta asks patients to exercise caution if they think of settling down and living a family life. "See, there's no known technique or procedure to prevent, slow down or reduce the risk of Huntington's disease. If someone is contemplating marriage and planning to expand his/her family, I'd rather suggest that he/she speak to a genetic counsellor about genetic testing to understand themaximum chances of having a child with a genetic condition," he alerts.

The Trigger

The culprit behind HD is a tiny snag in human DNA (Deoxyribonucleic Acid), which is a mutated HTT (Huntingtin. Mutations or genetic changes in this Huntingtin gene causes Huntington's disease, the neurodegenerative brain disorder) gene. "This gene goes haywire, producing a faulty protein that starts causing trouble in your brain cells. It's kind of like a recipe gone wrong," reports Dr Bhandari.

Indications

Symptoms of HD can be like a rollercoaster ride - both unpredictable and challenging.It affects a patient both physically and mentally.The tell-tale signs include:l Involuntary movements or uncontrolled jerks and twitching (chorea)l Difficulty with coordination (ataxia)l Trouble walking, difficulty swallowing (dysphagia)l Slurred speechl Cognitive decline like trouble with memory, focus and multitaskingl Depression and irritabilityl Emotional changes like mood swings.

Complications

A host of HD complications could include worsening of symptoms like:l Dementia (loss of brain function, memory loss, personality changes)l Physical injury from awkward movements or fallsl Inability to walk without external help or supportl Infections (pneumonia)l Seizures (early onset)l Difficulty swallowing, eating or drinking (malnutrition)

Unlocking The Genetic Code: AI Reveals New Insights Into Psychiatric Disorders

Figure: Illustration of mosaicism in eyes.

Getty

Recent breakthroughs in genetics research may have uncovered new genes underlying common psychiatric disorders. Schizophrenia and bipolar disorder affect more than 64 million people around the world. These disorders are strongly influenced by genetics. No one gene, however, determines one's risk of developing schizophrenia or bipolar disorder. Rather, it is likely that a host of genes contribute to risk. Using artificial intelligence, researchers at Stanford University now have uncovered complex variants throughout the human genome that may contribute to these psychiatric disorders. This new study suggests that mutations that occur after fertilization, such as genetic mosaicism, may be responsible for a number of psychiatric disorders including bipolar disorder and schizophrenia.

Think of a genome as a living book with instructions for every cell in the body. Our genes are the chapters. We have approximately 20,0000 genes that provide instructions for making proteins, the building blocks of life. The vast majority of our genes, however, are non-coding, meaning that they do not provide instructions for proteins. Nonetheless, these genes play an important role in genetics and regulating cell function.

Genetic variants, or spelling changes, in either a coding or non-coding region can interfere with how the cell translates specific instructions. A small typo may have little to no effect on how the book is read. However, larger spelling changes can lead to the deletion of a sentence or even a whole chapter. Without the correct instructions to produce specific proteins, these spelling changes can contribute to disorders that impact different aspects of our body.

Our genes are a combination of the DNA we inherit from our parents. We have two copies of each gene, one from mom and the other from dad. These randomly assorted gene pairs determine traits like hair texture, eye color, and even some health risks. Some traits are dominant, meaning that only one copy of the variant is needed for expression. Others are recessive and only show up if both copies are the same. This is referred to as Mendelian inheritance, named after Dr. Gregor Mende's initial observations of how genes are passed down in pea plants.

In the earliest stages of life, DNA undergoes multiple rounds of replication. Trillions of cell divisions occur, during which one cell splits into two identical daughter cells. DNA replication, however, is prone to mistakes. Each time a cell divides, tiny spelling errors are produced in the genome. Rapid replication during the first trimester of pregnancy, therefore, can introduce a host of genetic changes not seen in mom or dad. This is known as genetic mosaicism, where two or more genetically distinct cell populations are expressed in the body. Mosaicism can appear as two different color eyes, or alternating patterns of skin as shown below. A number of conditions have also been associated with mosaicism such as developmental delays, autism, epilepsy, and some cancers. We all have some degree of genetic mosaicism in our bodies. This is why identical twins can have different fingerprints.

Figure: Depiction of skin mosaicism.

Altmeyers Encyclopedia

Genetic variants can also be acquired throughout an individual's lifespan that further change our genome's mosaic. Changes in DNA may arise from exposure to chemicals or radiation, or from infections such as hepatitis B and C that corrupt the genetic material in a host cell. Other variants are acquired randomly. DNA may develop errors during replication and other normal cell functions. This damage is exacerbated by inflammation, aging, and lifestyle choices like smoking and poor diet. Pinpointing which variants contribute to certain disorders, therefore, can sometimes be a very complex process.

Whole genome sequencing (WGS) can help identify small changes in DNA. This genetic test maps an individual's entire genome using samples collected from blood or check swabs. Whole genome sequencing extracts the exact sequences that comprise each chapter of our DNA. The extracted sequences are then compared to reference genes from a typical human genome. Any difference between an individual's genome and the reference genome reveals a potential variant that could be associated with a disorder.

Alexander Urban, senior author of this study and Associate Professor at Stanford, describes, "Looking for only simple variations is like proofreading a book manuscript and searching exclusively for typos that change single letters. You are overlooking words that are scrambled or duplicated, or in the wrong order—you might even miss that half a chapter is gone." Certain disorders, in fact, may be linked to long, complex spelling changes in an individual's genes. It is made even more complicated by the fact that variants across several genes may overlap with more than one disorder.

Many psychiatric disorders are influenced by multiple changes across similar genes. Bipolar disorders and schizophrenia are prime examples of the complexity of the human genome. Hundreds of genetic variants have been identified that contribute to risk. Many of these genes are linked to brain development, immune system regulation, and neuron signaling pathways. The AKAP11 gene, in particular, has been found to be a strong risk factor for bipolar disorder, though recent studies in mice suggest that this gene may also be implicated in schizophrenia. Understanding how spelling changes in this gene interact with other high-risk variants may help to decipher what induces the onset of psychiatric symptoms.

In their study, Zhou et. Al compared the genomes of over 4,000 individuals around the world. Their entire DNA sequence was extracted using whole genome sequencing. The data was then uploaded into an AI algorithm trained to recognize dozens of genomes across diverse ancestry. This approach allowed researchers to match large, complex gene variants with specific health conditions.

The study specifically recruited individuals with known bipolar disorder or schizophrenia diagnoses and compared them to healthy controls. This type of approach is known as a genome-wide association study (GWAS). Genome-wide association studies compare the genes of individuals with a particular disease to a large cohort of controls. While this approach can tell us where variants are located, this information is often not precise. For instance, it may tell us that the book contains spelling changes on pages 122, 296, and 731, but not what type of errors are involved. The AI algorithm developed by Zhou et. Al adds more specificity. It highlights the changed word or sentence and reports whether it has been scrambled, duplicated, or deleted.

With more than 85% accuracy, the AI tool identified more than 8,000 complex variants. Many of these spelling changes were found in regions of the genome that provide instructions for brain function. To determine if these variants could be linked to psychiatric disorders, they extracted DNA from brain tissue samples of individuals affected by schizophrenia or bipolar disorder. The complex variants that they identified seemed to overlap with single variants found in other genome-wide association studies of these disorders. For instance, one complex variant that they found correlated with schizophrenia and bipolar disorder was the length of 4,700 base pairs, the basic unit of DNA. In the book analogy, base pairs are like the words in the book.

New innovations in genetic research are deepening our understanding of the human genome. By analyzing vast amounts of genetic data, AI technology is uncovering intricate relationships between large variants and certain psychiatric disorders. This not only enhances our understanding of the genetic basis of these disorders but also paves the way for personalized medicine. As we continue to uncover more of the human genome, future studies may reveal deeper insights into the genetic underpinnings of an array of disorders.

Existing USFDA-approved Drug Shows Promise For Two Rare Genetic Disorders: Researchers

Others You Array ( [galleryId] => 85391d2062c92e2fc164f6860e76eb763deafab664fda5e6 [thumbImage] => https://media.Ahmedabadmirror.Com/am/uploads/mediaGallery/image/1732732172238.Jpg-thmb [largeImage] => https://media.Ahmedabadmirror.Com/am/uploads/mediaGallery/image/1732732172238.Jpg-sldr [fullImage] => https://media.Ahmedabadmirror.Com/am/uploads/mediaGallery/image/1732732172238.Jpg-org [videoObj] => [caption] => genetic disorders [altText] => genetic disorders [description] => genetic disorders [title] => ) genetic disorders IANS

Nov 28, 2024 03:00 PMUPDATED: Nov 28, 2024 12:00 AM8 min read

A team of Canadian researchers has found an existing US Food and Drug Administration-approved drug that could significantly improve the quality of life for patients affected with Sandhoff and Tay-Sachs diseases — two rare genetic disorders. Sandhoff and Tay-Sachs diseases cause progressive damage to nerve cells in the brain and spinal cord; there is currently no cure for both disorders. 

After years of investigating the diseases' underlying mechanisms, the research at McMaster University identified a potential therapeutic compound: 4-phenylbutyric acid (4-PBA). 4-PBA is an FDA-approved drug that was initially developed for another condition. Suleiman Igdoura, a professor of biology and pathology at the varsity stated that Sandhoff and Tay-Sachs "are devastating diseases that are marked by progressive loss of motor functions — from sitting, standing, and swallowing to even breathing — as neurons in the nervous system die". 

In the study, published in the journal Human Molecular Genetics, the team tested 4-PBA in a mouse model of the disease. The results showed that 4-PBA significantly improved motor function, extended lifespan, and increased the number of healthy motor neurons.

"Patients often require intensive hospital care as symptoms worsen, and our current treatment options are severely limited," explains Igdoura. "But now, there's hope."

The team focussed on the late-onset of the rare diseases. They found that these originate in the spinal cord — where chronic stress on a cellular component called the endoplasmic reticulum triggers programmed cell death.​​​​​​​Igdoura said offering 4-PBA for "off-label use may provide hope and improve both life expectancy and quality of life for these patients." He noted that the findings may have broader implications, potentially informing research into other neurodegenerative diseases such as Alzheimer's and ALS.IANS

---