Category Archives: Genetic medicine

Genetic medicines have a capacity problem. The engineered viruses used to deliver them have limited room for their genetic cargo, which in turn limits the way diseases can be treatedif they can be treated at all. A new biotech company named Replay has assembled a suite of technologies that could enable it to deliver big genes or even multiple genes, and it has emerged with $55 million to advance its research.

The seed round announced Monday was led by KKR & Co. and OMX Ventures.

The delivery vehicle of choice for many experimental genetic medicines is the adeno-associated virus (AAV), which can be engineered to ferry DNA to target cells. The capacity of AAV is just under 5 kilobases (kb). San Diego-based Replay claims it can achieve a payload capacity up to 30 times greater. It aims to do so with its synHSV technology, which employs an engineered herpes simplex virus (HSV). In addition, Replays toolkit includes technologies that enable it to efficiently write its big genes and big DNA, and a technology that can produce off-the-shelf therapies.

The capacity limitation of AAV is apparent in the research of genetic medicines for Duchenne muscular dystrophy. Sarepta Therapeutics, Solid Biosciences and Pfizer have reached clinical testing with their respective gene therapies, each one engineered to deliver a functioning version of the gene needed to treat the inherited muscle-wasting disorder. But the genes that produce the key protein at the root of Duchenne are big, so the therapies are comprised of micro versions of the gene small enough to fit on an AAV vector.

Duchenne is one of the disease targets of Replay. The therapy in development for that muscle-weakening disorder is 14 kb, according to the companys website. But Replay wont be going directly head to head against the field of potential gene therapies for Duchenne. Under Replays business model, the various technologies it owns are developed in a disease-agnostic way. When Replay identifies an area that can specifically be addressed by one or more of its technologies, it forms a product company to pursue that area. The Duchenne research is housed in one such product company.

Technology and product development have different talent requirements, timelines, costs and cultures, Replay CEO and co-founder Lachlan MacKinnon said in a prepared statement. By separating technology development from product development, we have generated a model to accommodate these differences. Our ability to write and deliver big DNA has the potential to disrupt many areas of genomic medicine.

Replay says it has formed five product companies to date. In the eye, one company is focused on retinitis pigmentosa, a group of rare retinal disorders that leads to degeneration of photoreceptors. The Replay website lists two gene therapy constructs for retinitis pigmentosa: one is 7 kb and the other is 9 kb. A Replay skin product company is developing a treatment for dystrophic epidermolysis bullosa, an inherited disorder that leads to extremely fragile skin that is prone to widespread blistering. The experimental therapy of that company is 19.2 kb. Replays brain product company has the biggest of its genetic medicines in development, a 40 kb therapy for Parkinsons disease. A fifth product company is focused on enzyme writing.

There are other startups that, like Replay, are turning to AAV alternatives in the quest for better genetic medicines. Last month, Philadelphia-area startup Code Bio closed a $75 million Series A round of funding to support the development of synthetic DNA-based therapies for two lead indications, Duchenne and type 1 diabetes.

The new round of financing for Replay included participation from Artis Ventures, Lansdowne Partners, SALT, DeciBio Ventures and Axial.

Photo: iLexx, Getty Images

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Startup aiming to push boundaries of gene therapy nets $55M in seed cash - MedCity News

CAMBRIDGE, Mass., July 20, 2022 (GLOBE NEWSWIRE) -- SalioGen Therapeutics, a privately held biotechnology company developing Gene CodingTM, a new category of genetic medicine, today announced the expansion of its leadership team with the addition of five highly accomplished scientists, physicians and biotech industry leaders. The companys new appointments include:

As we continue to build on our foundational scientific discoveries and propel our research and development activities toward the clinic, we welcome Cathryn, Pat, Joe, Feng and Oleg to help drive our progress. The additions of these esteemed experts, each distinguished in their respective specialties, will serve to accelerate our growth by supporting core R&D activities, clinical preparations, and quality and operational needs, said Ray Tabibiazar, M.D., chief executive officer and chairman of SalioGen. We look forward to benefitting from their leadership as they help to maximize the potential impact of Gene Coding not only on the genetic medicines industry, but on patients around the world.

Cathryn Clary, M.D., MBA previously served as Senior Vice President of Medical at SSI Strategy, a medical consulting firm. She also served as the acting Chief Medical Officer at clinical-stage gene therapy company Solid Biosciences. Dr. Clary served as both Global Head of Policy and Patient Affairs in the Chief Medical & Patient Safety Office, as well as Chief Scientific Officer and Head of U.S. Medical Affairs and Clinical Development in the General Medicines Division at Novartis. Prior to her experience at Novartis, she served in several executive roles at Pfizer, whereshe was responsible for the medical aspects of Zoloft worldwide, and ultimately became the SVP of US Medical Affairs for the entire Pfizer portfolio across multiple therapeutic areas.

Pat Sacco is highly experienced as a biotechnology and life sciences executive in technical and general operations. Most recently, as an independent consultant, he has worked with a number of advanced therapy medicinal product (ATMP) biotech companies, CDMOs, and specialized program management clients. Previously, he was the Senior Vice President of Technical Operations at both Translate Bio and Shire (now Takeda), and prior to that held roles of increasing responsibility at Wyeth Biopharma (formerly Genetics Institute) and Genzyme. He has contributed to the development, manufacturing, and commercialization of the enzyme replacement therapies REPLAGAL, ELAPRASE, and VPRIV.

Joe Senn, Ph.D. has experience with nearly all therapeutic modalities, including small molecules, biologics, antisense, gene editing and mRNA therapeutics. He most recently served as the Vice President of Nonclinical Development at Moderna Therapeutics for eight years, where he and his team were responsible for progressing over 40 candidates into the clinic. Prior to Moderna, Dr. Senn served as Site Head for Drug Safety at Takeda Pharmaceuticals, where he oversaw development of all immunology products across the portfolio.

Feng Yao, Ph.D. is the inventor of Invitrogen/Thermo Fisher Scientifics T-Rex tetracycline gene switch, a powerful and specific mammalian transcription gene switch. Using this technology, Dr. Yao has established several unique approaches for the genetic engineering of novel recombinant viruses for use in clinical applications across infectious diseases, cancers and neural regeneration. His T-REx technology is widely used and referenced in publications and patent applications, including productions of several FDA approved antibody therapeutics and novel COVID-19 viral vector-based vaccine candidates developed by AstraZeneca and Johnson and Johnson. Before joining SalioGen Therapeutics, Dr. Yao was an Associate Professor of Surgery at the Brigham and Womens Hospital and Harvard Medical School.

Oleg Iartchouk, Ph.D. has built and led multiple genomics technologyteams that werepart ofstartup and large global pharmaceutical and biotechnologycompanies.Prior to joining SalioGen, Dr. Iartchouk served as the Global Head of the global Genomics Platform Group at the Novartis Institute for Biomedical Research, which established genomics applications several fields to advance Novartiss cell and gene therapy portfolioincluding CAR-T cell(Kymriah) and gene (Zolgensma) therapies.Dr. Iartchouk also built the Biomarkers Discovery group at the clinical diagnostics company Natera and the Applied Genomics team at Sanofi Oncology.

About SalioGen TherapeuticsSalioGen Therapeutics has launched Gene CodingTM, a genetic medicine platform, to develop durable, broadly applicable genetic medicines, using its Exact DNA Integration TechnologyTM (EDITTM) platform. EDIT is based on the novel mammal-derived genomic engineering tool, for use in potentially curative genetic medicines. SalioGen is focused on developing therapies for more patients with inherited diseases that are beyond what is addressable with current technologies, initially focusing on inherited macular disorders and inherited lipid disorders.

For more information, please visit http://www.saliogen.com, or follow us on Twitter and LinkedIn.

Forward-Looking StatementsThis press release contains forward-looking statements. Words such as may, believe, will, expect, plan, anticipate, estimate, intend and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. Forward-looking statements are based upon current estimates and assumptions and include statements regarding the additions of the esteemed experts serving to accelerate SalioGens growth by supporting core research & development activities, clinical preparations, and quality and operational needs, benefitting from their leadership as they help to maximize the potential impact of Gene Coding not only on the genetic medicines industry, but on patients around the world, and the potential of SalioGens Gene Coding approach, including its use in potentially curative genetic medicines. While SalioGen believes these forward-looking statements are reasonable, undue reliance should not be placed on any such forward-looking statements, which are based on information available to us on the date of this release. These forward-looking statements are subject to various risks and uncertainties, many of which are difficult to predict, that could cause actual results to differ materially from current expectations and assumptions from those set forth or implied by any forward-looking statements. Important factors that could cause actual results to differ materially from current expectations include, among others, the ability of SalioGen to position multiple therapeutic programs for clinical development, the ability of SalioGen to continue building out its Gene Coding platform, expand the companys team, establish manufacturing and automation capabilities critical for Gene Coding and accelerate the advancement of SalioGens preclinical programs as planned, the ability of SalioGen to use its Gene Coding platform and Exact DNA Integration Technology in potentially curative genetic medicines. All forward-looking statements are based on SalioGens expectations and assumptions as of the date of this press release. Actual results may differ materially from these forward-looking statements. Except as required by law, SalioGen expressly disclaims any responsibility to update any forward-looking statement contained herein, whether as a result of new information, future events or otherwise.

Corporate Contact:Sung You, M.S., MBASalioGen Therapeuticsinvestors@saliogen.com

Media Contact:Amy Jobe, Ph.D.LifeSci Communications315-879-8192ajobe@lifescicomms.com

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SalioGen Therapeutics Strengthens its Leadership Team to Advance its Gene Coding Platform - BioSpace

Were thankful to be able to partner with Sitruna to bring accurate genetic pet testing to more pet owners in Europe, said Noam Pik, CEO of Orivet

LAKE WORTH, Fla. (PRWEB) July 26, 2022

Orivet, a pioneer in international genetic pet testing and personalized medicine announced its recent partnership with Sitruna, an Amazon logistics and marketing specialist company that specializes in leveraging its experience and industry knowledge to help create and meet demand on Amazon.

This new partnership will center around the growing demand for Orivets pet and breeder products on Amazon in Europe. As specialists in listing and logistics, Sitruna will help Orivet connect with pet owners, breeders, and veterinarians who are looking for evidence-backed and comprehensive methods to discover a pets genetic makeup, possible hereditary diseases, and health requirements.

With diseases such as obesity and other inherited variants becoming more scrutinized by pet owners in Europe, the demand for accurate hereditary genetic testing has skyrocketed in recent years with an expectation for the global market to reach $28.5 billion by 2026 a substantial increase from the $990 million valuation in 2020.

Were thankful to be able to partner with Sitruna to bring accurate genetic pet testing to more pet owners in Europe, said Noam Pik, CEO of Orivet.More people than ever are conscious of their pets long-term journey and want whats best for them, and we want to help these owners better map out a healthier life for their best friend.

About Orivet Genetic Pet CareOrivet Genetic Pet Care is a leading personalized-medicine organization offering innovative health care solutions for breeders, veterinarians, and pet owners. The organization was founded in 2010, on the premise that each pet is unique, with its own set of specific traits, behaviors, genetic health needs, and inherent risks. Orivet works with veterinarians, pet owners, and responsible pet breeders to provide practical, evidence-based platforms focused on identifying risk and improving clinical outcomes.For more information please visit https://www.orivet.com

About Sitruna Sitruna is an innovative IT services company that leverages its knowledge of listing optimization, PPC, photography, and logistics to help businesses gain market share, stay ahead of their competition, and maximize ROI on Amazon. Backed by decades of experience in eCommerce and numerous Amazons Choice badges, Sitruna backs up its five-star reviews with five-star results.For more information please visit https://www.sitruna.com

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Orivet Partners with Sitruna to Expand Ecommerce Footprint in Europe - PR Web

image:Study codirectors Dr. Pablo Garca-Pava and Dr. Jess Gonzalez Mirelis. view more

Credit: CNIC

Combining a persons genetic profile with imaging data obtained by cardiac magnetic resonance accurately predicts the prognosis of patients with dilated cardiomyopathy, the most frequent cause of heart failure.

This is the finding of a Spanish study published in the European Journal of Heart Failure and coordinated by Dr. Pablo Garca-Pava, investigator at the Centro Nacional de Investigaciones Cardiovasculares (CNIC), a cardiologist at Hospital Puerta de Hierro Majadahonda in Madrid, and a member of the Spanish research network on cardiovascular disease (CIBERCV). The study is the largest in the world to correlate the genetic profiles of dilated cardiomyopathy patients with cardiac magnetic resonance data collected over a long follow-up period.

Dilated cardiomyopathy is the most frequent cause of heart disease in young people and the leading cause of heart transplantation in the world. The disease affects 1 person in every 250 of the general population and is characterized by an enlargement of the heart accompanied by a decline in its capacity to pump blood.

Patients with this condition are at high risk of arrhythmias and sudden cardiac death.

The study examined genetic data collected from 600 patients in 20 Spanish hospitals between 2015 and 2020. The investigators demonstrated that a combination of specific genetic traits with the presence of fibrosis detected by cardiac magnetic resonance imaging accurately identifies those patients who will develop malignant arrhythmias or severe complications of heart failure.

Dr. Jess Gonzalez Mirelis, a cardiologist at Hospital Puerta de Hierro and codirector of the study, explained that there is currently a lack of good prognostic markers for patients with dilated cardiomyopathy. As a result, to prevent sudden death, patients are routinely selected for more aggressive interventions, such as the placement of a defibrillator device, based on the degree of weakening of the hearts pumping action.

The new study shows that classifying patients according to their genetic profile and the presence of fibrosis detected by cardiac magnetic resonance imaging gives a much more accurate indication of patient risk than the extent of weakening of cardiac pumping capacity, the method used until now; the problem with the current method is that some patients with low-grade cardiac weakening develop complications, whereas others with extensive weakening are stable and dont develop problems over the long term, said Dr. Garca Pava.

The researchers found that patients lacking genetic alterations and showing no sign of fibrosis had a very good prognosis, with little risk of sudden death irrespective of the weakening of cardiac pumping capacity.

According to the authors, the study opens the way to a more personalized approach to dilated cardiomyopathy, with each patient receiving the most appropriate treatment based on a precise cardiological assessment.

The findings of this study allow dilated cardiomyopathy patients to be treated according to their specific characteristics and open the way to the application of personalized medicine in this area of cardiology, concluded Dr. Garca-Pava.

The following centers participated in the study: Hospital Universitario Puerta de Hierro, IDIPHISA; CIBER Cardiovascular; Hospital General Universitario Gregorio Maran; Instituto de Investigacin Biomdica de Salamanca (IBSAL)- Complejo Asistencial Universitario de Salamanca; Universidad de Salamanca; Hospital Universitario Virgen de la Arrixaca de Murcia; Hospital Universitari Vall d'Hebron, Vall d'Hebron Instituto de Recerca (VHIR), Universitat Autonoma de Barcelona; Complejo Hospitalario de Navarra; Instituto de Investigacin Biomdica de A Corua (INIBIC), Complexo Hospitalario Universitario de A Corua; Universidad de A Corua; Complejo Hospitalario Universitario de Cceres; Hospital Universitario Virgen de la Victoria IBIMA, Mlaga; Instituto de Ciencias del Corazn (ICICOR); Hospital Clnico Universitario Valladolid; Hospital General Universitario de Alicante, Instituto de Salud e Investigacin Biomdica; Hospital Universitario 12 de Octubre, Instituto de Investigacin i+12; Hospital Clnico, IDIBAPS, Universitat de Barcelona; Instituto de investigacin Sanitaria de Santiago; Complexo Hospitalario Universitario de Santiago; Hospital Universitario Virgen de las Nieves; Hospital Universitario Son Llatzer & IdISBa; Hospital Universitario Virgen del Roco; Hospital Univesitari Dr. Josep Trueta; Instituto del Corazn & Hospital Universitario Germans Trias, and Universidad Francisco de Vitoria (UFV).

The study was funded by grants from the Instituto de Salud Carlos III with cofunding from the European Regional Development Fund (A way to build Europe) and the European Social Fund (Investing in Your Future).

About the CNIC

The Centro Nacional de Investigaciones Cardiovasculares (CNIC), directed by Dr. Valentn Fuster, is dedicated to cardiovascular research and the translation of knowledge gained into real benefits for patients. The CNIC, recognized by the Spanish government as a Severo Ochoa center of excellence, is financed through a pioneering public-private partnership between the government (through the Carlos III Institute of Health) and the Pro-CNIC Foundation, which brings together 12 of the most important Spanish private companies.

European Journal of Heart Failure

Randomized controlled/clinical trial

People

Combination of late gadolinium enhancement and genotype improves prediction of prognosis in non-ischaemic dilated cardiomyopathy

22-Jul-2022

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Spanish scientists combine genetic and imaging data to improve the treatment of dilated cardiomyopathy - EurekAlert

(Boston)Black Americans are twice as likely as white Americans to have Alzheimers disease (AD) independent of genetic risk. Since perceived racism contributes to racial health disparities in cardiovascular disease (CVD) risk factors, which also are risk factors for AD,it also has a significant impact on the racialhealth disparity in AD. Despite this knowledge, little is known about whether and how chronic experiences of racism contribute to poor brain health.

Karin Schon, PhD, assistant professor of anatomy & neurobiology at Boston University School of Medicine (BUSM), aims to address this pressing issue. She has been awarded a five-year, $3.9 million R01 grant from the National Institutes of Health. Her objective is to investigate the impact of racism burden on brain health in themedial temporal hippocampal (MTH) memory and prefrontal-executive systems in older Black adults and to examine potentially underlying biological mechanisms. The MTH and prefrontal systems are brainsystems that show profound neurodegeneration in AD.

We hypothesize that cognitively healthy Black seniors with higher racism burden will show greater CVD risk and poorer MTH and prefrontal system integrity than those who have lower lifetime racism burden, explained Schon who also is a faculty affiliate at the BU Center for Anti-Racist Research.

Schon believes that CVD risk and mental health may explain the relationship between racism burden and neurocognitive integrity, suggesting poor cardiovascular/cerebrovascular healthas a mechanism underlying the relationship between racism burden and poor brain health in the MTH and prefrontal brain systems in Black seniors.

Her investigative team is not only diverse in expertise, but also racially and ethnically. Collaborators on this project include BUs Yvette Cozier, DSc; Robert Stern, PhD; Emelia Benjamin, MD and Yorghos Tripodis, PhD. BU alumna Uraina Clark, PhD from Icahn School of Medicine at Mount Sinai along with Angie Sanchez, MD and Jonathan Jackson, PhD from Massachusetts General Hospital.

Schon, received a joint BA/MA degree in psychology from the University of Hamburg in Germany in 1998 and her PhD from the department of psychology at Boston University in 2005. Her dissertation focused on functional neuroimaging studies of working memory and long-term (episodic) memory formation. In 2010, she received a Pathway to Independence Career Development award from the National Institute on Aging to investigate the effects or cardio-respiratory fitness and exercise on the function and structure of the medial temporal hippocampal memory system. In 2013, she joined BUSMs department of anatomy & neurobiology where she is the Director of the Brain Plasticity and Neuroimaging Laboratory.

Her brain plasticity research focuses on modulators of the MTH system across the lifespan. Currently, she is investigating the role of aerobic exercise, aging and chronic psychosocial stress, as modulators of cognitive function and brain health in aging and AD. With her cognitive neuroscience research on chronic psychosocial stress she aims to take an anti-racist perspective by focusing on the impact of interpersonal and institutional racism on brain health in Black adults. The long-term goal of this research to contribute to health policy change from a cognitive neuroscience perspective with the goal to eliminate brain health inequities.

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BU researcher receives $3.9M NIH grant to examine the impact of racism on brain aging, cardiovascular disease risk among older black adults -...

Preimplantation genetic testing (PGT) is a procedure used to identify genetic abnormalities in embryos created with in vitro fertilization (IVF). PGT is performed before embryos are transferred to the uterus. The goal of PGT is to significantly reduce the chances of transferring an embryo with a specific genetic condition or chromosome abnormality.

Yes. There are three types of PGT:

PGT-A can be performed for any IVF cycle, but the decision to have this testing is complex and should be made after careful discussion with your physician or genetic counselor. PGT-A is most often considered for patients who have had recurrent pregnancy losses (miscarriages), multiple failed IVF cycles, a prior pregnancy or child with certain chromosome abnormalities, or based on maternal age. However, there is notable controversy about the benefits of PGT-A (see questions 14 and 15).

By contrast, PGT-M and PGT-SR are only performed when the patient, their partner and/or their donor have abnormal genetic test results that put the embryos at increased risk for a genetic disorder. PGT-M is an option for patients with an increased risk for a single gene disorder in their embryos such as cystic fibrosis or sickle cell anemia. PGT-SR is an option for patients who have a chromosome translocation or inversion. PGT-M and PGT-SR allow patients the opportunity to reduce the risk of having an affected child prior to becoming pregnant.

All three types of PGT are performed in a similar fashion. The patient goes through their IVF cycle and egg retrieval as recommended by their physician. Their embryo(s) are monitored in our laboratory until day 5 or 6 when they are referred to as blastocysts. At that time, a small number of cells are biopsied (removed) from each embryo and shipped to an outside laboratory for PGT. The cells are taken from a part of the blastocyst called the trophectoderm, which will eventually form the placenta. These cells are expected to be representative of the rest of the embryo; however, this may not always be the case due to circumstances such as mosaicism (see question 13). The embryo(s) must be frozen while PGT is performed. An embryo with normal PGT results would be selected, thawed, and transferred to the uterus at a later date.

In addition to the biopsied cells from the embryo(s), other DNA samples are often required for PGT. In order to perform PGT-A, blood samples from the patient and their partner must be collected in our office prior to the egg retrieval. Please see question 6 if you are using an anonymous donor.

For PGT-M and PGT-SR, the required samples vary. The laboratory performing PGT-M or PGT-SR will evaluate your unique case and determine what samples are needed to develop testing for your embryo(s). This may include blood and/or saliva from the individuals contributing the eggs and sperm as well as from other family members. In some cases, the male partner may also need to provide a sperm sample.

Possibly. For PGT-A, we have laboratory options that do not require additional samples from the sperm or egg donor. For PGT-M or PGT-SR, each case is unique and must be reviewed by a genetic counselor. In some cases, it may not be possible for the laboratory to develop reliable testing for embryos created using an anonymous donor.

Yes. The biopsy process, which removes cells from each embryo for PGT, has a small chance of damaging the embryo. Additionally, since the embryo(s) must be frozen while PGT is performed, they must also undergo a thawing procedure prior to transfer. In our centers experience, the survival rate of embryos that were biopsied and later thawed is 97%.

The decision to have PGT needs to be made well in advance of your IVF cycle. If PGT is part of your plan, our office will open a case with the laboratory. This allows them to check your insurance benefits and confirm payment options.Additionally, blood samples from the patient, their partner and/or donor, and sometimes other family members must be collected in advance (see question 5).

For PGT-M and PGT-SR, there is a test development phase during which the laboratory confirms if they will be able to reliably detect the specific genetic condition in the patients embryo(s). The test development phase can take up to 8-12 weeks after all required DNA samples are received. This process must be fully completed before an IVF cycle (stimulation medications) will be started.

Yes. PGT-A screens for chromosome abnormalities that occur randomlyin a portion of any womans eggs or mans sperm. Chromosome abnormalities are common in embryos and are not usually inherited.Therefore, we do not expect patients to have a family history of any chromosome conditions.

The laboratory we use most often (Natera) uses a single nucleotide polymorphism (SNP) microarray and DNA samples from the individuals who contributed the eggs and sperm to perform PGT-A. Nateras testing can detect three types of chromosome abnormalities.It is primarily designed to ensure an embryo has the correct number of chromosomes (euploidy). PGT-A screens embryos for whole missing chromosomes (monosomy), whole extra chromosomes (trisomy), or an entire extra set of 23 chromosomes (triploidy).Second, PGT-A at Natera screens for missing or extra pieces of chromosomes (deletions or duplications). These deletions and duplications must be large, accounting for 15% of the total length of that chromosome, to potentially be detected. Finally, PGT-A at Natera screens for uniparental disomy (UPD) of chromosomes 6, 7, 11, 14, and 15. UPD occurs when an embryo receives two copies of a chromosome from one biological parent, and no copies from the other. UPD of these five chromosomes can result in poor pregnancy outcomes or a child with serious health issues.

Chromosome abnormalities are common in embryos. Overall, the laboratory we use most often (Natera) reports that 51% of the day 5 embryo biopsies they test have normal chromosomes and 49% have abnormal chromosomes.The percentage of chromosomally normal embryos expected is most strongly influenced by the age of the person providing the egg (see question 12).

Chromosome abnormalities can happen in any embryo or pregnancy simply by chance. However, the chance for missing or extra chromosomes (aneuploidy) does increase with the age of the person providing the egg. For a woman who is less than 30 years old, the laboratory we use most often (Natera) finds that 31% of the day 5 embryos have abnormal PGT-A results. For women ages 30-34, the frequency of abnormal PGT-A results increases slightly to 36%. For women ages 35-39, 50% of day 5 embryos have abnormal PGT-A results. For women ages 40 or older, Natera reports that 68% of day 5 embryos have abnormal PGT-A results.

Please remember these are averages so you may have a greater or smaller percentage of normal embryos than expected based on age. In some IVF cycles, a patient may not have any embryos with normal PGT-A results to transfer. It is also important to keep in mind that the number of embryos a woman will have available to test also tends to decrease with age.

Mosaicism refers to a mixture of two or more types of cells within the same embryo. On day 5, an embryo is made up of approximately 120 cells.The lab will remove 5-10 of these cells for PGT. We expect all of the embryos cells to be identical so testing this small sample will give us accurate information about the whole embryo in most cases. However, if the embryo has mosaicism, the 5-10 cells which are biopsied may not accurately represent all of the cells of the embryo.For instance, the biopsied cells may be chromosomally normal, but other untested cells within the embryo are abnormal.Conversely, the 5-10 biopsied cells may be chromosomally abnormal, but other cells within the embryo are normal.

Sometimes the 5-10 biopsied cells contain a mixture of chromosomally normal and abnormal cells.If mosaicism is reported by the laboratory, those embryos would only be considered for transfer if the patient has no chromosomally normal (euploid) embryos available. The decision to use a mosaic embryo for transfer is complicated and requires careful genetic counseling. Data about the potential of mosaic embryos to result in a healthy pregnancy and child are still being gathered. Multiple studies have found mosaic embryos have poorer outcomes compared to those with normal chromosome results.

There are several potential benefits of PGT-A. For patients with several good quality embryos, PGT-A is an additional tool that may assist in the selection of the best embryo for transfer. For patients whose embryos have PGT-A, a single chromosomally normal embryo is transferred reducing the chance of multiples (e.g. twins or triplets). PGT-A may also be helpful when a patient has excess embryos they plan to store for future use. Since embryos with aneuploidy are more likely to result in a failed IVF cycle or miscarriage, PGT-A provides additional information about the reproductive potential of those embryos. PGT-A also reduces the likelihood of the birth of a child with a detectable chromosome condition like Down syndrome. If you are interested in learning more about PGT-A, we recommend you discuss this test with your physician and our genetic counselor. We can review your individual circumstances to help you determine if PGT-A is right for you.

Yes. First, PGT-A adds significant additional cost that may not be covered by insurance (see question 21). Some patients may have to undergo more than one IVF cycle in order to get a chromosomally normal embryo for transfer, further increasing their costs. Second, the embryo(s) must be frozen while PGT is performed so patients are unable to do a fresh transfer. A frozen embryo transfer will be scheduled after the PGT results are available. Third, the PGT process poses a small risk to the embryo(s) (see question 7). Finally, although uncommon, inaccurate PGT results may lead to the transfer of an embryo with a chromosome abnormality that was not detected or the non-transfer of an embryo with potential to result in a healthy pregnancy.

PGT-M or PGT-SR are options for patients with a personal or family history of a specific genetic condition or chromosome rearrangement who wish to greatly reduce the chance of having a child affected by that condition. If you are interested in PGT-M or PGT-SR, the first step is for our genetic counselor and the laboratory to review your abnormal genetic test results. The laboratory will determine if they can develop a test for your embryos that can reliably identify which are affected. Unfortunately, PGT-M or PGT-SR may not be able to be performed successfully in all cases due to technical limitations.

With the exception of a few chromosome conditions such as Down syndrome, Turner syndrome, Klinefelter syndrome, trisomy 13, trisomy 18, PGT-A does nottest embryos for any specific genetic diseases or syndromes.

In order to perform PGT-M or PGT-SR, you must be able to provide documentation of the specific genetic abnormality. For PGT-M, a copy of the abnormal genetic test results must be submitted to the laboratory. These results must contain the specific gene and the specific variant(s) for which the patient wants to test their embryo(s). For PGT-SR, a copy of the abnormal chromosome study (karyotype) documenting the specific translocation or inversion must be submitted.

The results of PGT are highly accurate; however, it is still considered a screening test. This means false positives and false negatives can occur.If you transfer an embryo that has been tested by PGT, it is recommended you consider confirming the normal results through diagnostic prenatal testing such as chorionic villus sampling (CVS) or amniocentesis. Non-invasive prenatal testing (NIPT) can also be used as a first-line screen for a limited number of chromosome abnormalities during pregnancy. However, NIPT (like PGT) is also a screening test with the potential for false positives or false negatives. Your physician or a genetic counselor can review these options with you in more detail as there are risks and limitations for each test that should be considered carefully.

No.PGT only screens for certain chromosome abnormalities (PGT-A or PGT-SR) or one specific genetic condition (PGT-M).Every pregnancy has a risk of approximately 3-5% to result in a child with a genetic condition or birth defect.There is no genetic test that can eliminate this risk or identify all diseases or birth defects.There is always a risk for a child to have a medical issue, regardless of the screening performed.

PGT is always optional. If PGT is not right for you, there are several genetic testing options that can be performed during a pregnancy. First, non-invasive prenatal testing (NIPT) screens for certain chromosome abnormalities by analyzingfetal DNA in a sample of a pregnant womans blood. It is also sometimes referred to as cell-free fetal DNA testing.NIPT always screens for Down syndrome (trisomy 21), trisomy 18, and trisomy 13. Some versions of NIPT may also screen for the sex chromosomes (X and Y), other trisomies, triploidy (having an extra copy of every chromosome), and certain microdeletions (missing sections of a chromosome that cause known syndromes such as 22q11.2 deletion syndrome). The benefits of NIPT are that it can be doneas early as 9 weeksof pregnancy,and since it is performed on a blood sample from the pregnant woman, there is no risk to the pregnancy. However, NIPT is still a screening test meaning false positives and false negatives can occur. NIPT does not typically screen for single-gene conditions.

Chorionic villus sampling (CVS) and amniocentesis are two additional options for prenatal genetic testing. CVS can be performed in the first trimester between 10-13 weeks gestation, while amniocentesis can be performed in the second trimester between 15-24 weeks gestation. CVS and amniocentesis can be used to test for chromosome abnormalities and/or a specific single-gene condition. Both provide highly accurate genetic results.While CVS and amniocentesis offer advantages over NIPT, both of these tests are invasive so they do pose a risk for miscarriage or other complications.If you are interested in prenatal genetic testing, we recommend you review the benefits and limitations of these options with a physician or genetic counselor.

The cost of PGT depends on many factors including the type of PGT being performed, the number of embryos being tested, and which laboratory is performing the test. Our office and the performing laboratory can assist you in determining your insurance coverage and expected out-of-pocket costs for PGT.

As an example, the laboratory we use most often (Natera) offers self-pay pricing for those without insurance coverage. The self-pay price for PGT-A or PGT-SR for a Robertsonian translocation is $1,795 for up to eight embryos. The self-pay price for PGT-SR for a reciprocal translocation or inversion is $3,675 for up to eight embryos. The self-pay price for PGT-M for one genetic condition is $6,000 for up to sixteen embryos.There is also a $375 fee for shipping the embryo biopsy samples to Natera, which must almost always be paid out-of-pocket.

Once the laboratory receives the embryo biopsy samples and has received payment for the testing, results are expected in approximately 7-10 days.

Your physician or genetic counselor will call you with your PGT results. At that time, we will review how many embryos are appropriate for transfer.

An embryo with normal PGT-A results is predicted to have the correct number of chromosomes and no evidence of large chromosome deletions or duplications or uniparental disomy (see question 10). PGT-A cannot detect all chromosome abnormalities such as small extra or missing pieces of chromosomes (microdeletions and microduplications). PGT-A cannot detect any single-gene disorders. Normal PGT-A results cannot rule out the possibility a child may be born with a birth defect, autism, developmental delay/intellectual disability, or serious health issues that are not caused by detectable chromosome abnormalities. Normal PGT-A results cannot guarantee a successful IVF cycle or prevent miscarriage.

Abnormal PGT-A results mean the laboratory detected a chromosome abnormality.Embryos with abnormal PGT-A results are not recommended for transfer because they are expected to result in a failed IVF cycle, miscarriage, or the birth of a child with serious health issues.

An embryo with normal PGT-M results is predicted to be free of the genetic condition for which it was tested. For autosomal recessive conditions, PGT-M will also identify whether the normal embryo is a carrier or not. Since carriers of autosomal recessive conditions are not expected to have symptoms, those embryos may be transferred if the patient wishes. Abnormal PGT-M results mean the embryo is expected to be affected with the condition for which it was tested. Therefore, those embryos would not be recommended for transfer.

An embryo with normal PGT-SR results is predicted to have the correct amount of each chromosome with no detectable missing or extra pieces. The laboratory will look closely at the chromosomes involved in the translocation or inversion. It is important to know that, at this time, PGT-SR does not distinguish between embryos with normal chromosomes and those with a balanced translocation or inversion.Since carriers of a balanced translocation or chromosome inversion are typically healthy, those embryos are reasonable to transfer. A routine chromosome study (karyotype) can be done through CVS, amniocentesis, or on a blood sample after delivery to determine if the child inherited the balanced translocation or inversion.

We strongly encourage all patients who are interested in PGT to have an appointment with our genetic counselor.This consultation will ensure you fully understand the risks, benefits, and limitations of this testing. The genetic counselor will also determine if there are any additional concerns based on your personal and family history that should be addressed prior to your IVF cycle.

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Preimplantation Genetic Testing - Fertility & Reproductive Medicine Center

The University of Michigan Genetic Counseling Programis one of the most well-established programs in the country and exemplifies our long history of innovation in clinical service and education in genetics and genomics. Michigan graduates emerge as extremely well-rounded genetic counselors, who are ready to meet the current challenges in clinical genomic medicine and are able to help guide the evolving practice of genetic counseling and genomic medicine.

The vision of the University of Michigan Genetic Counseling Program is to train genetic counselors that are able to meet the current challenges and to help shape the future of genetic counseling and genomic medicine.

Our mission is to provide an individualized, integrated and supportive graduate training environment comprised of:

Most importantly, our graduate training program is responsive to the interests and unique needs of individual students.

Contact us at UMGenetics@med.umich.edu.

Follow us on Instagram! @umgcp

The University of Michigan Masters in Genetic Counseling program is accredited by the Accreditation Council for Genetic Counseling (ACGC), located at 7918 Jones Branch Drive, Suite 300, McLean, VA 22102 USA, web addresswww.gceducation.org. ACGC can be reached by phone at 913.222.8668.Pleaseclick herefor more information regarding professional licensure.

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Genetic Counseling Program | Human Genetics | Michigan Medicine

If you have family members with Parkinsons disease, or if you yourself have the disease and are concerned about your childrens chances of developing it, youve probably already wondered: Is there a gene that causes Parkinsons disease? How direct is the link?

About 15 percent of people with Parkinsons disease have a family history of the condition, and family-linked cases can result from genetic mutations in a group of genes LRRK2, PARK2, PARK7, PINK1 or the SNCA gene (see below). However, the interaction between genetic changes, or mutations, and an individuals risk of developing the disease is not fully understood, says Ted Dawson, M.D., Ph.D., director of the Institute for Cell Engineering at Johns Hopkins.

Heres what you need to know:

Theres a long list of genes known to contribute to Parkinsons, and there may be many more yet to be discovered. Here are some of the main players:

SNCA: SNCA makes the protein alpha-synuclein. In brain cells of individuals with Parkinsons disease, this protein gathers in clumps called Lewy bodies. Mutations in the SNCA gene occur in early-onset Parkinsons disease.

PARK2: The PARK2 gene makes the protein parkin, which normally helps cells break down and recycle proteins.

PARK7: Mutations in this gene cause a rare form of early-onset Parkinsons disease. The PARK7 gene makes the protein DJ-1, which protects against mitochondrial stress.

PINK1: The protein made by PINK1 is a protein kinase that protects mitochondria (structures inside cells) from stress. PINK1 mutations occur in early-onset Parkinsons disease.

LRRK2: The protein made by LRRK2 is also a protein kinase. Mutations in the LRRK2 gene have been linked to late-onset Parkinsons disease.

Among inherited cases of Parkinsons, the inheritance patterns differ depending on the genes involved. If the LRRK2 or SNCA genes are involved, Parkinsons is likely inherited from just one parent. Thats called an autosomal dominant pattern, which is when you only need one copy of a gene to be altered for the disorder to happen.

If the PARK2, PARK7 or PINK1 gene is involved, its typically in an autosomal recessive pattern, which is when you need two copies of the gene altered for the disorder to happen. That means that two copies of the gene in each cell have been altered. Both parents passed on the altered gene but may not have had any signs of Parkinsons disease themselves.

Our major effort now is understanding how mutations in these genes cause Parkinsons disease, says Dawson. SNCA, the gene responsible for making the protein that clumps in the brain and triggers symptoms, is particularly interesting.

Our research is trying to understand how alpha-synuclein works, how it travels through the brain, says Dawson. The latest theory is that it transfers from cell to cell, and our work supports that idea. Weve identified a protein that lets clumps of alpha-synuclein into cells, and we hope a therapy can be developed that interferes with that process.

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The Genetic Link to Parkinson's Disease | Johns Hopkins Medicine

(Reuters Health) - The experimental Arrowhead Pharmaceuticals drug fazirsiran can reduce the accumulation of a mutant protein by 83% among people with alpha1-antitrypsin deficiency (AAT) disease, according to results from an open-label phase 2 trial involving 16 volunteers.

The condition is a rare genetic liver disease wherein a mutant protein, known as Z-AAT, accumulates in the liver and can lead to fibrosis, then cirrhosis or portal hypertension, and eventually hepatic decompensation or hepatocellular carcinoma. There is no approved treatment.

Fazirsiran, an RNA interference therapeutic, was given in one of two doses on day 1, week 4, week 16, and then every 12 weeks.

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At week 24 and 48, a median 83% of the Z-AAT in the liver was gone.

"Fibrosis regression was observed in 7 of 15 patients and fibrosis progression in 2 of 15 patients after 24 or 48 weeks," the research team led by Dr. Pavel Strnad of RWTH Aachen University in Germany report in the New England Journal of Medicine.

The team also saw improvements in liver enzyme concentrations.

"Because the liver is a regenerative organ, removal of the Z-AAT hepatic insult is expected to yield clinical benefit," they write.

However, "Despite marked reductions in liver Z-AAT concentrations in all the patients, reductions in mutant protein concentrations did not uniformly translate into regression of fibrosis during the first 24 or 48 weeks of treatment," the authors note.

Although no side effects prompted anyone to leave the trial, there were four serious adverse events coinciding with the treatment: diverticulitis, dyspnea, viral myocarditis, and vestibular neuronitis. The Strnad team said all of those problems resolved and "each of the four patients continues to receive fazirsiran treatment in the extension period."

Milder side effects included arthralgia and increased blood creatinine kinase.

A problem was considered an adverse event if it emerged or worsened after the first dose of the drug.

Arrowhead conducted the trial. The company released topline results of the study in November. The updated results were presented Saturday at the annual meeting of the European Association for the Study of the Liver.

Fazirsiran was previously known as ARO-ATT.

SOURCE: https://bit.ly/3ne0DXV The New England Journal of Medicine, online June 25, 2022.

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Drug reduces mutant protein that can lead to fibrosis in rare genetic liver disease - Reuters

EDELIFE Phase II trial explores potential of pioneering prenatal treatment for XLHED

GENEVA and Castres, France, July 1, 2022 /PRNewswire/ --The EspeRare Foundation and the Pierre Fabre group announced today that the first patient in the EDELIFE clinical trial has received the three rounds of injection as planned. The pivotal trial is the first-of-its-kind, as the treatment is given to the XLHED (X-linked Hypohidrotic Ectodermal Dysplasia)-affected baby while inside his mother's womb. The trial intends to confirm the efficacy and safety of ER004 given as a pre-natal treatment to XLHED-affected boys.

EDELIFE A prenatal study for XLHED affected boys

XLHED is a very rare and debilitating congenital disease which affects approximately 4/100,000 live male births every year. This genetic disorder is a dermatologic-related condition which leads to abnormal development of the skin, sweat glands, sebaceous glands, hair, oral cavity and respiratory mucosal glands resulting in serious clinical manifestations such as hyperthermia, craniofacial anomalies and recurrent respiratory infections.

The EDELIFE clinical trial is a confirmatory study that will investigate the efficacy and safety of intra-amniotic ER004 administrations as a prenatal treatment for male foetuses who have been confirmed to have XLHED. ER004 is a pioneering in-utero therapy designed to replace the function of endogenous Ectodysplasin A1 (EDA1), a protein key to the normal development of ectodermal structures in the foetus. If successful, ER004 has the potentialto become the first approved 'single-course treatment', administered during the second and third trimesters of pregnancy.

"It is an exciting time for the Hypohidrotic Ectodermal Dysplasia community and for prenatal medical research. For the first time, we can hope to correct major symptoms of XLHED for those who are diagnosed before birth," said Caroline Kant, the Co-founder and CEO of the EspeRare Foundation. "We need the support of the XLHED community to ensure that those who may benefit from this unique treatment are aware of the EDELIFE trial."

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A target number of 15 to 20 baby boys with XLHED will be treated within the EDELIFE trial across 8 centres in Europe and the USA. Clinical centres for the study are now open in Germany, France, Italy, Spain, the United Kingdom and will be open shortly in the USA. A dedicated web site (www.EDELIFEclinicaltrial.com) is available for interested families who want to learn more about the clinical trial and the conditions for enrolment. Beyond the initial English version, it will progressively be developed in German, French, Italian and Spanish.

"We are committed to supporting pregnantwomen with a confirmed diagnosis of XLHED in their treatment journey for their unborn baby boys," said Dr Deborah Szafir, Executive Vice President, Head of Medical and Patient Consumer Division at Pierre Fabre. "15 to 20 patients in the clinical trial may seem like a very small number, but given how rare the condition is, it is essential we facilitate the process of enrolment into the study as much as possible. This includes facilitating the pregnant women's travel to a nearby country if there is no investigational site open in their own country. We feel very proud at Pierre Fabre to support those with rare dermatologic diseases as we have already successfully done in infantile hemangiomas".

In the main study phase of the EDELIFE clinical trial, efficacy and safety of approximately 15 treated children will be assessed up to 6 months of age and safety of the mothers will be assessed up to 1 month after delivery. In the long-term follow-up phase, efficacy and safety of the treated children will be assessed up to 5 years of age. The main phase of the clinical study is expected to last until 2025.

The ER004 in XLHED program has received a wide range of regulatory support, including Breakthrough Therapy Designation in 2020 by the US Federal Drug Administration (FDA). Its clinical development also benefits from the European Medical Agency's (EMA) PRIME (PRIority MEdicines) program.

Details also available on http://www.clinicaltrials.gov. Study NCT04980638

About XLHEDXLHED is a severegenetic disorder that affects the structure of the ectoderm, the most exterior part of the three primary germ layers formed during early embryonic life, from which the skin and its appendages are derived. XLHED is caused by mutations in EDA, a gene that encodes an important developmental signalling protein, EDA1. The absence of functional EDA1 in the ectoderm results in abnormal development of the skin, sweat glands, sebaceous glands, hair, oral cavity, and respiratory mucosal glands.

About ER004ER004 is a pioneering in-utero therapy designed to replace the function of endogenous Ectodysplasin A1 (EDA1), a protein key to the normal development of ectodermal structures in the foetus. ER004 is a recombinant, soluble, and humanized form of EDA1 that is given as a single course treatment and delivered through intra-amniotic injections during the late stage of pregnancy. This approach has already demonstrated a promising potential in humans where it restored sweat gland function in three patients treated in this fashion by Prof. Holm Schneider at the University Hospital Erlangen in Germany. First results were published in the New England Journal of Medicine1 and in the British Journal of Clinical Pharmacology2 as well as featured in Nature Medicine's Research Highlights3.

About the EspeRare foundationEspeRare is a Swiss non-profit organization founded in 2013 that is committed to improve the lives of children with life-threatening rare diseases. EspeRare addresses the unmet medical needs of these children by uncovering the potential of existing treatments. EspeRare's innovative model combines pharmaceutical know-how with philanthropic, public and private investments to develop and bring to life these discontinued therapies. With its unique patient-centred approach to drug development, EspeRare engages the patient community at each step of the process, with the intent of giving children and their families fair access to these therapies and a new hope for the future.For more information, please visit http://www.esperare.org

About Pierre FabrePierre Fabre is the 2nd largest dermo-cosmetics laboratory in the world, the 2nd largest private French pharmaceutical group and the market leader in France for products sold over the counter in pharmacies. Its portfolio includes several medical franchises and international brands including Pierre Fabre Oncology, Pierre Fabre Dermatology, Eau Thermale Avne, Klorane, Ducray, Ren Furterer, A-Derma, Naturactive, Pierre Fabre Oral Care.In 2021, Pierre Fabre generated 2.5 billion in revenues, 66% of which came from international sales.Established in the South-West of France since its creation, the Group manufacturs over 95% of its products in France and employs some 9,500 people worldwide. Its products are distributed in about 115 countries. Pierre Fabre is 86%-owned by the Pierre Fabre Foundation, a government-recognised public-interest foundation, and secondarily by its own employees through an international employee stock ownership plan.Further information about Pierre Fabre can be found at http://www.pierre-fabre.com, @PierreFabre.

References

Prenatal Correction of X-Linked Hypohidrotic Ectodermal Dysplasia. Schneider H, Faschingbauer F, Schuepbach-Mallepell S, Krber I, Wohlfart S, Dick A, Wahlbuhl M, Kowalczyk-Quintas C, Vigolo M, Kirby N, Tannert C, Rompel O, Rascher W, Beckmann MW, Schneider P. N Engl J Med 2018; 378: 1604-1610

Safety and immunogenicity of Fc-EDA, a recombinant ectodysplasin A1 replacement protein, in human subjects. Krber I, Klein OD, Morhart P, Faschingbauer F, Grange DK, Clarke A, Bodemer C, Maitz S, Huttner K, Kirby N, Durand C, Schneider H. Br J Clin Pharmacol. 2020;86(10):2063-2069

In utero correction of a genetic disorder. Stower H.Nature Medicine 2018; 24: 702

Photo -https://mma.prnewswire.com/media/1851585/edelife.jpgLogo -https://mma.prnewswire.com/media/1688212/Pierre_Fabre_and_EspeRare_Logo.jpg

CONTACTS :EspeRare Foundationfoundation@esperare.org

Pierre Fabreanne.kerveillant@pierre-fabre.com

(PRNewsfoto/Pierre Fabre; EspeRare Foundation)

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SOURCE Pierre Fabre, EspeRare Foundation

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Pierre Fabre and the EspeRare Foundation administer investigational treatment to first patient in EDELIFE clinical trial for rare genetic disease,...