Category: Genetics

Categories : Genetics PaediatricsTags :

Cancer Drugs May Help Children with Severe Congenital Myopathy

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Photo by National Cancer Institute on Unsplash

For the first time, children with severe congenital myopathy may have a better chance at learning to walk thanks to a new therapeutic approach using enzyme-inhibiting cancer drugs, as reported in the journal eLife.

Professor Susan Treves remembers seeing one child affected by the condition at the age of six months. The boy seemed more like a newborn, she said. Today, several years later and thanks to intensive physiotherapy, he is at least able sit. “He made it,” she said. As yet there is no cure for children like this one. Their first priority is survival. Another child with mutations in the same gene as the boy mentioned above, did not survive. However, his genetic alterations now form the basis of a therapeutic approach presented by the research group led by Professors Susan Treves and Francesco Zorzato.

The affected gene is for the calcium channel RYR1 in skeletal muscle. The mutations render the gene useless, which severely impacts muscle function. The researchers used the gene alterations found in a patient, as a template to develop a mouse model for this type of congenital myopathy. “The mice don’t die, but their muscle system is severely impaired,” says Treves. “They’re smaller, and move much less.” With a combination of two drugs, however, the research team was able to significantly improve muscle function and movement of the mice.

The therapy is based on the observation that certain enzymes are produced in excessive quantities in the skeletal muscles of affected patients. These enzymes – histone deacetylases and DNA methyltransferases – affect how densely genes are packed, making them less accessible to the cellular machinery that reads them and translates them into instructions for protein production.

Prof Treves and her team used inhibitors against these enzymes, which are already approved as cancer drugs or are in clinical trials. The treatment significantly improved the mice’s movement ability, although they were still smaller. No adverse side effects were noted during the study period.

The approach is still far from being a clinical therapy, said Prof Treves. “But it’s a first step in the right direction.” The researchers aim to further optimise the treatment and test combinations of newly developed drugs targeting the same enzymes for even better effects. “We anticipate around about two more years of optimisation and testing before we can initiate a phase I clinical trial,” she said.

For Profs Treves and Zorzato, these first promising results are the culmination of 10 years of research – especially as Prof Zorzato was the one who first isolated the gene affected in these muscle disorders years ago. “We’ve now succeeded in bridging the gap from the isolation of the affected gene to a therapeutic approach,” said Prof Treves.

Source: University of Basel

Categories : Cancer GeneticsTags :

How Cancer Cells Repair their DNA so Quickly

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DNA repair
Source: Pixabay/CC0

Research into how the body’s DNA repair process works has made a discovery into how the process works, and by understanding how cancer cells repair their DNA so rapidly may lead to potent new chemotherapy treatments.

One of the great mysteries of medical science is the ability of DNA to be repaired after damage, but complicating the study of this is how different pathways are involved in the repair process over the cell’s life cycle. In one of the repair pathways known as base excision repair (BER), the damaged material is removed, and proteins and enzymes work together to create DNA to fill in and then seal the gaps.

In a study appearing in Proceedings of the National Academy of Sciences, Eminent Professor Zucai Suo led a team that discovered that BER has a built-in mechanism to increase its effectiveness: it just needs to be captured at a very precise point in the cell life cycle.

In BER, an enzyme called polymerase beta (PolyB) fulfils two functions: It creates DNA, and it initiates a reaction to clean up the leftover ‘chemical junk’. Through five years of study, Prof Suo’s team learned that by capturing PolyB when it is naturally cross-linked with DNA, the enzyme will produce new genetic material 17 times faster than when the two are not cross-linked. This suggests that the two functions of PolyB are interlocked, not independent, during BER.

The research improves the understanding of cellular genomic stability, drug efficacy and resistance associated with chemotherapy.

“Cancer cells replicate at high speed, and their DNA endures a lot of damage,” Prof Suo said. “When a doctor uses certain drugs to attack cancer cells’ DNA, the cancer cells must cope with additional DNA damage. If the cancer cells cannot rapidly fix DNA damage, they will die. Otherwise, the cancer cells survive, and drug resistance appears.”

This research examined naturally cross-linked PolyB and DNA, unlike previous research that mimicked the process. Studies had previously identified the enzymes involved in BER but did not fully grasp how they work together.

“When we have nicks in DNA, bad things can happen, like the double strand breaking in DNA,” said Thomas Spratt, a professor of biochemistry and molecular biology at Penn State University College of Medicine who was not a part of the research team. “What Zucai found provides us with something we didn’t understand before, and he used many different methods to reach his findings.”

Source: Florida State University

Categories : Diseases, Syndromes and Conditions GeneticsTags :

A Life-changing Genetic Cure for Sickle Cell Patient

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Sickle cell disease occurs in people who inherit two copies of the sickle cell gene, one from each parent. This produces abnormal haemoglobin, called haemoglobin S. Credit: Darryl Leja, National Human Genome Research Institute, National Institutes of Health

Jimi Olaghere, who had suffered all his life from the chronic pain of sickle cell disease, recently received a genetic cure decades sooner than he would have believed possible.

Mr Olaghere is one of the first seven sickle cell patients who received a new gene-editing treatment going through its first clinic trials in the US. “It’s like being born again,” he said, adding that it has changed his life. “When I look back, it’s like, ‘Wow, I can’t believe I lived with that.'”

Mr Olaghere, 36 said: “You always have to be in a war mindset, knowing that your days are going to be filled with challenges.”

Sickle cell disease is caused by a mutated gene that results in abnormal haemoglobin, leading to blood cells becoming more rigid and taking on their characteristic sickle shape. These malformed cells often get stuck in blood vessels, giving rise to ischaemias and an increase in cardiovascular disease risk and organ damage. Mr Olaghere may need a hip replacement due to avascular necrosis.

The disease also causes chronic pain, which he likened to “shards of glass flowing through your veins or someone taking a hammer to your joints.”

Severe pain episodes known as crises are the hallmark of sickle cell disease. For years, Mr Olaghere was hospitalised on a monthly basis. Winters worsened the problem as the cold restricted surface blood vessels, increasing the risk of blockages. He moved to a warmer city, and became a tech entrepreneur as he didn’t think any employer would be sympathetic to going to the hospital so often.

His family urged him to participate in clinical trials or receive a bone marrow transplant. However, he thought it would take too much time and instead pinned his hopes on DNA editing “in the future, probably 20 to 50 years from now”.

But in 2019 he read about a new gene editing therapy and emailed the medical team right away. When he learned he was accepted, he said it was “the best Christmas present ever”. As the pandemic hit and flights were cancelled, he was still able to make the four-hour drive for treatment appointments.
In order to genetically edit his stem cells the stem cells were flushed out of his bone marrow and into the bloodstream for collection.

“You sit there for eight hours and this machine is literally just sucking all the blood out of you,” he said.

The process left him physically and mentally drained, and still needed  blood transfusions. Mr Olaghere had to go through this process, the most difficult of all for him, four times. 

The key to the treatment lies not in correcting the genetic defect that produces the cell but rather sidestepping it by getting the body to use an alternative: foetal haemoglobin 

Ordinarily, at around 40 weeks of pregnancy, a genetic switch called BCL11A is flipped and the body starts producing adult haemoglobin – which is the only form affected by sickle cell disease. 

“Our approach is to turn that switch off and increase the production of foetal haemoglobin again, basically turning the clock back,” explained Dr Haydar Frangoul, who treated Mr at the Sarah Cannon Research Institute.

Mr Olaghere’s stem cells were sent to Vertex Pharmaceuticals’ laboratories for genetic editing. By September 2020, the engineered cells were ready to be infused into his body. “It was the week of my birthday, actually. So it was almost like getting a new life,” he recalled.

The original faulty stem cells that remained in his body were killed off with chemotherapy, and then genetically engineered replacements were infused into his body to produce sickle-free blood.

“I remember waking up without any pain and feeling lost,” he said. “Because my life is so associated with pain, it’s just a part of who I am. It’s weird now that I don’t experience it any more.'”

Dr Frangoul said that the first seven patients’ results have been “nothing short of amazing” and represented a “functional cure” for their disease.
“What we are seeing is patients are going back to their normal life, none have required admission to hospital or doctor visits because of sickle cell related complications,” Dr Frangoul said.

So far, the genetic technique has been conducted on 45 patients with either sickle cell disease or beta thalassaemia. However, the data are still being gathered.

Source: BBC News

Categories : Cardiovascular Disease GeneticsTags :

Prevalence of Cardiac Arrhythmia Risk Genes Greater Than Believed

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Source: Pixabay/CC0

By sequencing genes linked to cardiac arrhythmia risk in more than 20 000 people without an indication for genetic testing, scientists were able to identify possible pathogenic variants in 0.6% of individuals, according to a study published in Circulation.

This rate is higher than those previously reported, according to Carlos G. Vanoye, PhD, research associate professor of Pharmacology and a co-author of the study.

“This study suggests the prevalence of genetic susceptibility to cardiac arrhythmia may be underestimated,” Dr Vanoye said.

The American College of Genetics and Genomics (ACMG) currently recommends that incidentally discovered pathogenic or likely pathogenic variants in 73 Mendelian disease genes be reported back to patients. This includes many genetic variants associated with congenital cardiac arrhythmias, causing irregular heartbeats which can lead to stroke or sudden cardiac death.

However, the pathogenicity of many genetic variants in these known arrhythmia genes is uncertain, and classification of these variants is still in the early stages.

“A person can carry a disease-causing gene variant but exhibit no obvious signs or symptoms of the disease,” Dr Vanoye said. “Because the genes we studied are associated with sudden death, which may have no warning signs, discovery of a potentially life-threatening arrhythmia gene variant can prompt additional clinical work-up to determine risks and guide preventive therapies.”

The current study used data from the Electronic Medical Records and Genomics sequencing (eMERGEIII) study. The eMERGEIII study investigated the feasibility of population genomic screening by sequencing 109 genes implicated across the spectrum of Mendelian (single inherited gene mutation) diseases in over 20 000 individuals, returning variant results to the participants, and using Electronic Health Record (EHR) and follow-up clinical data to ascertain patient phenotypes.

In the current study, investigators analysed 10 arrhythmia-associated genes in individuals without an indication for genetic testing.

The researchers determined the functional consequences of these variants of uncertain significance and used the data to refine the assessment of pathogenicity. In the end, they reclassified 11 of these variants: three that were likely benign and eight that were likely pathogenic.

In all, 0.6% of the studied population had a variant that increases risk for potentially life-threatening arrhythmia and there was overrepresentation of arrhythmia phenotypes among these patients. This is a rate higher than previously known for genetic arrhythmia syndromes (approximately 1 in 2000) and illustrates the potential for population genomic screening, Dr Vanoye said.

“Population genomic screening can positively affect public health. Many rare, disease-associated variants can be found this way which can then help determine the disease-risk of the carriers of these variants,” Dr Vanoye said. “Although the costs of genomic screening may be currently high, assessing patient risk followed up by clinical care would reduce the financial and emotional cost of the disease.”

Source: Northwestern Medicine

Categories : GeneticsTags :

Rapidly Correcting Genetic Disorders

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Image source: Pixabay

Researchers have developed a new method to precisely and rapidly correct genetic alterations in cultured patient cells.

The genetically corrected stem cells are produced from a 2–3 mm skin biopsy taken from patients with different genetic diseases. The corrected stem cells are essential in the research and for the development of new therapies for the diseases in question.

The scientists based the new method on previous groundbreaking research in the fields of stem cells and gene editing; the first technique is the invention of induced pluripotent stem cells, iPSCs from differentiated cells, which won the Nobel in 2012. The other technique is the CRISPR-Cas9 ‘gene scissors’, which got the prize in 2020. The new method combines these techniques to correct gene alterations that cause inherited diseases, creating fully functional new stem cells.

The researchers aim to eventually produce autologous cells with therapeutic properties. The use of the patient’s own corrected cells could help in avoiding the immunological challenges hampering the organ and tissue transplantation from a donor. The new method was developed by PhD student Sami Jalil  and is published in Stem Cell Reports.

More than 6000 inherited diseases are known to exist, which are caused by various gene alterations. Currently, some are treated with a cell or organ transplant from a healthy donor, if available.

“Our new system is much faster and more precise than the older methods in correcting the DNA errors, and the speed makes it easier and diminishes also the risk of unwanted changes,” commented adjunct professor Kirmo Wartiovaara, who supervised the work.

“In perfect conditions, we have reached up to 100 percent efficacy, although one has to remember that the correction of cultured cells is still far away from proven therapeutic applications. But it is a very positive start” Prof Wartiovaara added.

Source: University of Helsinki

Categories : Genetics Immune SystemTags :

Differences in Influenza Responses According to Genetic Ancestries

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Photo by Andrea Piacquadio on Unsplash

Researchers have uncovered differences in immune pathway activation to influenza infection between individuals of European and African genetic ancestry, according to a study published in Science. Many of the genes that were associated with these immune response differences to influenza are also enriched among genes associated with COVID disease severity. 

“The lab has been interested in understanding how individuals from diverse populations respond differently to infectious diseases,” said first author Haley Randolph, a graduate student at the University of Chicago. “In this study, we wanted to look at the differences in how various cell types respond to viral infection.”

The researchers examined gene expression patterns in peripheral mononuclear blood cells, a diverse set of specialised immune cells that play important roles in the body’s response to infection. These cells were gathered from men of European and African ancestry and then exposed the cells to flu in a laboratory setting. This let the team examine the gene signatures of a variety of immune cell types, and observe how the flu virus affected each cell type’s gene expression.

The results showed that individuals of European ancestry showed an increase in type I interferon pathway activity during early influenza infection.

“Interferons are proteins that are critical for fighting viral infections,” said senior author Luis Barreiro, PhD, Associate Professor of Medicine at UChicago. “In COVID-19, for example, the type I interferon response has been associated with differences in the severity of the disease.”

This increased pathway activation hindered the replication of the virus more and limited viral replication later on. “Inducing a strong type I interferon pathway response early upon infection stops the virus from replicating and may therefore have a direct impact on the body’s ability to control the virus,” said Barreiro. “Unexpectedly, this central pathway to our defense against viruses appears to be amongst the most divergent between individuals from African and European ancestry.”

The researchers saw a variety of differences in gene expression across different cell types, suggesting a constellation of cells that work together to fight disease.

Such a difference in immune pathway activation could explain influenza outcome disparities between different racial groups; Non-Hispanic Black Americans are more likely to be hospitalised due to the flu than any other racial group.

However, these results are not evidence for genetic differences in disease susceptibility, the researchers point out. Rather, possible differences in environmental and lifestyle between racial groups could be influencing gene expression, and affecting the immune response.

“There’s a strong relationship between the interferon response and the proportion of the genome that is of African ancestry, which might make you think it’s genetic, but it’s not that simple,” said Barreiro. “Genetic ancestry also correlates with environmental differences. A lot of what we’re capturing could be the result of other disparities in our society, such as systemic racism and healthcare inequities. Although some of the differences we show in the paper can be linked to specific genetic variation, showing that genetics do play some role, such genetic differences are not enough to fully explain the differences in the interferon response.”

These differences in viral susceptibility may not be confined to just influenza. Comparing a list of genes associated with differences in COVID severity, the researchers found that many of the same genes showed significant differences in their expression after flu infection between individuals of African and European ancestry.

“We didn’t study COVID patient samples as part of this study, but the overlap between these gene sets suggests that there may be some underlying biological differences, influenced by genetic ancestry and environmental effects, that might explain the disparities we see in COVID outcomes,” said Barreiro.

As they explore this further, the researchers hope to figure out which factors contribute to the differences in the interferon response, and immune responses more broadly, to better predict individual disease risk.

Source: EurekAlert!

Categories : Genetics NeurologyTags :

Scientists Identify A New Recessive Neurodevelopmental Disorder

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Image source: Pixabay

In the Journal of Clinical Investigation, researchers have reported a rare neurodevelopmental condition characterised by intellectual disability, ataxia with cerebellar hypoplasia and delayed puberty with hypogonadotropic hypogonadism (HH).

Patients with this unusual combination of conditions were referred to Mehul Dattani (UCL), and affected individuals were found to carry the same homozygous mutation in the PRDM13 gene, which encodes a chromatin modifying factor that contributes to regulating cell fate. Intriguingly, an unaffected heterozygous carrier of this mutation was identified by screening 42 unaffected individuals in the Maltese population, suggesting that this mutation is present at low levels in the population.

The researchers set out to model this condition and identify the underlying causes using a PRDM13-deficient mouse model. The researchers found evidence that both the cerebellar hypoplasia and reproductive phenotypes resulted from defects in the specification of specific populations of GABAergic neuronal progenitors in the developing cerebellum and hypothalamus, respectively.

The results indicate that this condition results from abnormal cell fate specification during development. Consequently, the hypoplastic cerebellum is deficient in molecular layer interneurons, which play critical roles in regulating cerebellar circuits. In the hypothalamus, fewer Kisspeptin neurons, which are important regulators of gonadotropin releasing hormone and puberty, were present in PRDM13 mutant mice.

Together, these findings identify PRDM13 as a critical regulator of neuronal cell fate in the cerebellum and hypothalamus, providing a mechanistic explanation for the co-occurrence of hypogonadism and cerebellar hypoplasia in this syndrome.

Source: King’s College London

Categories : GeneticsTags :

The Need for an African Genetic Library

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Source: Mart Production on Pexels

Earlier this year, UCT professor Ambroise Wonkam published the Three Million African Genomes (3MAG) project in Nature, which he said started with a “crazy idea”. Now, it looks like his vision is starting to take shape.

The idea of creating a huge library of genetic information about the population of Africa emerged from his work on how genetic mutations among Africans contribute to conditions like sickle-cell disease and hearing impairments.

African genes contain great genetic variation, more than that seen outside of Africa. As he explained, “We are all African but only a small fraction of Africans moved out of Africa about 20–40 000 years ago and settled in Europe and in Asia.”

Another concern for Prof Wonkam is equity, saying: “Too little of the knowledge and applications from genomics have benefited the global south because of inequalities in health-care systems, a small local research workforce and lack of funding.”

Thus far only about 2% of genomes mapped are African, a good proportion of which are African American. This stes from a lack of prioritising funding, policies and training infrastructure, he says, but it also means the understanding of genetic medicine as a whole is lopsided. By studying African genomes, injustics can be corrected, such as finding that genetic risk profiles based on Europeans could be misleading for those of African descent.

To address these disparities, Prof Wonkam and other scientists are speaking to governments, companies and professional bodies across Africa and internationally, in order to build up capacity over the next decade to make the vision a reality.

He expects three million is the number needed to accurately map genetic variations across Africa. The project will take a decade, he says, costing around $450m per year, with industry already showing interest. 

Biotech firms welcome prospects of new data
The Centre for Proteomic and Genomic Research (CPGR) in Cape Town works with biotech firm Artisan Biomed on a variety of diagnostic tests. Gaps in the applicability of genetic data to the local population are a challenge for the firm, it said.

A genetic mutation in someone could be found but it would be uncertain if that variation is associated with a disease, especially as a marker for that particular population.

“The more information you have at that level, the better the diagnosis, treatment and eventually care can be for any individual, regardless of your ethnicity,” said Dr Lindsay Petersen, the company’s chief operations officer.

Artisan Biomed says the data it collects feeds back into CPGR’s research – allowing them to design a better diagnostic toolkit that is better suited to African populations, for instance.

Dr Judith Hornby Cuff said that the 3MAG project would help streamline processes and improve research, and one day could provide cheaper, more effective and more accessible health care, particularly in the strained South African system.

Prof Wonkam acknowledged that while the costs are huge, the project will “improve capacity in a whole range of biomedical disciplines that will equip Africa to tackle public-health challenges more equitably”.

“We have to be ambitious when we are in Africa. You have so many challenges you cannot see small, you have to see big – and really big,” he said.

Source: BBC News

Categories : General Interest GeneticsTags :

Chief Sitting Bull’s DNA Matched to Living Descendant

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By Orlando Scott Goff – Heritage Auctions, Public Domain, https://commons.wikimedia.org/w/index.php?curid=27530348

A team of researchers led by the University of Cambridge has proven a man’s claim to be the great-grandson of legendary Native American leader Sitting Bull has been confirmed using DNA extracted from Sitting Bull’s scalp lock. This is the first time ancient DNA has been used to confirm a familial relationship between living and historical individuals.

The researchers used a new method to analyse family lineages using ancient DNA fragments, which searches for ‘autosomal DNA’ in the genetic fragments extracted from a body sample. Since half of our autosomal DNA is inherited from the father and half from the mother, this means genetic matches can be checked regardless of whether an ancestor is on the father or mother’s side of the family.

Autosomal DNA from Lakota Sioux leader Sitting Bull’s scalp lock was compared to DNA samples from Ernie Lapointe and other Lakota Sioux. The resulting match confirms that Lapointe is Sitting Bull’s great-grandson, and his closest living descendant.

“Autosomal DNA is our non-gender-specific DNA. We managed to locate sufficient amounts of autosomal DNA in Sitting Bull’s hair sample, and compare it to the DNA sample from Ernie Lapointe and other Lakota Sioux – and were delighted to find that it matched,” said senior author of the study, Professor Eske Willerslev in the University of Cambridge’s Department of Zoology and Lundbeck Foundation GeoGenetics Centre, who also developed the new DNA analysis technique.

Lapointe said: “over the years, many people have tried to question the relationship that I and my sisters have to Sitting Bull.”

Lapointe believes that Sitting Bull’s bones currently lie at a site in Mobridge, South Dakota, in a place that has no significant connection to Sitting Bull and the culture he represented. He also has concerns about the care of the gravesite. There are two official burial sites for Sitting Bull – at Fort Yates, North Dakota and Mobridge – and both receive visitors.

Lapointe, with the help of the DNA evidence confirming his heritage, now hopes to rebury the great Native American leader’s bones in a more appropriate location.

The new technique can be used when very limited genetic data are available, as was the case in this study. This could be used to match up long-dead historical figures and their living descendants.

The technique could also be used on old human DNA that might previously have been considered too degraded to analyse – for example in forensic investigations.

“In principle, you could investigate whoever you want – from outlaws like Jesse James to the Russian tsar’s family, the Romanovs. If there is access to old DNA – typically extracted from bones, hair or teeth, they can be examined in the same way,” said Willerslev, who is a Fellow of St John’s College, Cambridge.

It took the scientists 14 years to find a way of extracting useable DNA from the 5-6cm piece of Sitting Bull’s hair, which was extremely degraded, having been stored for over a century at room temperature in a museum before it was returned to Lapointe and his sisters in 2007.

In traditional DNA analysis, which searches for a genetic match between specific DNA in the Y chromosome passed down the male line, or, in females, specific DNA in the mitochondria passed from a mother to her offspring. Neither are particularly reliable, and in this case neither could be used as Lapointe claimed to be related to Sitting Bull on his mother’s side.

Tatanka-Iyotanka, better known as the Native American leader and military leader Sitting Bull (1831–1890), led 1,500 Lakota warriors at the Battle of the Little Bighorn in 1876 and wiped out US General Custer and five companies of soldiers.

“Sitting Bull has always been my hero, ever since I was a boy. I admire his courage and his drive. That’s why I almost choked on my coffee when I read in a magazine in 2007 that the Smithsonian Museum had decided to return Sitting Bull’s hair to Ernie Lapointe and his three sisters, in accordance with new US legislation on the repatriation of museum objects,” said Willerslev.

He added: “I wrote to Lapointe and explained that I specialised in the analysis of ancient DNA, and that I was an admirer of Sitting Bull, and I would consider it a great honour if I could be allowed to compare the DNA of Ernie and his sisters with the DNA of the Native American leader’s hair when it was returned to them.”

Until this study, the familial relationship between LaPointe and Sitting Bull was based on birth and death certificates, a family tree, and a review of historical records. This new genetic analysis lends further credence to his claims. Before the remain can be reburied, they will have to be analysed in the same to ensure a genetic match to Sitting Bull.

Before the remains from the Mobridge burial site can be reburied elsewhere, they will have to be analysed in a similar way to the hair sample to ensure a genetic match to Sitting Bull. 

Source: Cambridge University

Categories : GeneticsTags :

Briefly Quitting Cannabis Can Reduce its Genetic Effects in Sperm

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Photo by Grav on Unsplash

While cannabis use may impact some autism-linked genes in men’s sperm, briefly quitting cannabis over time may significantly lower many of those effects, according to a new study.

This study, published online in Environmental Epigenetics, followed several other studies at Duke University that linked cannabis use to epigenetic changes (alteration of expression without changing genes) present in sperm, including genes in early development.

This new study aimed to find out if cannabis abstinence could reduce such epigenetic changes. The results showed marijuana users who stopped using cannabis for 77 days produced sperm lacking most of the significant changes found when the men were actively using cannabis.
Study author Susan Murphy, PhD, associate professor in the Department of Obstetrics & Gynecology at Duke University School of Medicine, said the results may suggest that marijuana abstinence could result in washout of sperm with the drug’s epigenetic effects. More research is needed for lingering epigenetic effects after abstinence, but there are immediate implications for some.

“Stopping cannabis use for as long as possible – at least for a 74-day period before trying to conceive – would be a good idea,” she said. “If someone is really serious about that, I would say to stop cannabis use for as long as possible prior to conception – meaning multiple spermatogenic cycles.”

“Is it going to fix everything? Probably not,” Prof Murphy said. “We know there are other epigenetic changes that emerged in the ‘after’ sample that we don’t understand yet – and some of those changes are troubling, like an enrichment of other genes related to autism. But it does appear that the things that were the most severely affected in the ‘before’ sample seem to be mitigated by the abstinence period in the ‘after’ samples.”

The study took a baseline sperm sample from marijuana users and non-marijuana users, then followed both groups as the marijuana-using group abstained from cannabis for 77 days – a period spanning the average time it takes for a sperm to mature, which is 74 days. Researchers collected a second sample from both groups after the 77-day period.

During baseline tests, the marijuana-consuming group produced sperm with changes in line with previous studies, which showed altered epigenetic information, including changes in genes linked to early development and neurodevelopmental disorders. With a 77-day abstinence period, this same group was able to produce sperm that had far less altered epigenetic information at the same genes.

The post-abstinence sample was also much more in line with the samples produced by the non-cannabis-using control group.

Prof Murphy says further research is needed to see if the remaining epigenetic changes observed in the sperm of cannabis consumers, when they abstain, carry over into development after fertilisation.

“We don’t know yet whether the alterations that we’re seeing are at genes that have a stable characteristic,” she said, “or if they are in genes that get reprogrammed and really are going to be of no consequence to the child.”

In any case, Prof Murphy says this work is not about legalisation, rather about giving people the power to make informed decisions for themselves.

“I think that we deserve to know what the biological consequences are so that if you are planning to have a child, or even for your own health, you can make an informed decision about whether you want to use it and when, and that’s not really an option right now because we don’t know what it does,” Prof Murphy said.

Source: Duke University