Category Archives: Gene Medicine

This article was originally published here

Annu Int Conf IEEE Eng Med Biol Soc. 2021 Nov;2021:2437-2443. doi: 10.1109/EMBC46164.2021.9630460.

ABSTRACT

Among males, prostate cancer (Pca) is the cancer type with the highest prevalence and the second leading cause of cancer deaths. The current screening methods for prostate cancer lack effectiveness such as prostate-specific antigen (PSA) and digital rectal exam (DRE). Machine learning models have been used to predict Pca progression, Gleason score, and laterality. In this research paper, we have employed novel Machine learning techniques such as Bayesian approach, Support vector machines (SVM), Decision Trees, Logistic Regression, K-Nearest Neighbors, Random Forest and AdaBoost for detecting malignant prostate cancers from benign ones. Moreover, different feature extracting strategies are proposed to improve the detection performance and identify potential genomic biomarkers. The results show the Lasso feature set yielded high performance from the models with SVM achieving exemplary classification accuracy of 97%. The Lasso and SVM combination reported many significant biomarker genes and gene mutations including but not restricted to CA2320112, CA2328529, and CA2436168.

PMID:34891773 | DOI:10.1109/EMBC46164.2021.9630460

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Identification of Significantly Expressed Gene Mutations for Automated Classification of Benign and Malignant Prostate Cancer - DocWire News

More than 2.5 million Americans have a chronic condition arising in early childhood that can negatively impact their education, job performance and employability well into adulthood.

There is no known cure, and existing treatments are often minimally effective. Yet for those with persistent, developmental stuttering, there is new hope, thanks to groundbreaking research led by scientists at Vanderbilt University Medical Center in Nashville, Tennessee, and Wayne State University in Detroit, Michigan.

In two papers published this week, Jennifer "Piper" Below, PhD, and Shelly Jo Kraft, PhD, describe a "genetic architecture" for developmental stuttering and report the discovery of new genetic variations associated with the condition.

The researchers said that these findings, which were published in The American Journal of Human Genetics andHuman Genetics and Genomics Advances, and studies like them have the potential to identify therapeutic directions that could improve outcomes for people who stutter.

"It's clear that in populations, stuttering is polygenic, meaning that there are multiple different genetic factors contributing to and protecting people from risk," said Below, associate professor of Medicine at VUMC. "That was something that had not been clearly shown before these studies."

The new revelations will have a huge impact on people who stutter and on the parents of children affected by the condition, predicted Kraft, associate professor of Communication Sciences and Disorders and director of the Behavior, Speech & Genetics Lab at Wayne State University.

"It's a piece of themselves that they can then understand," she said, "instead of living a lifetime of experiencing this difference in their speech and never knowing why."

With the help of colleagues in Ireland, England, Israel, Sweden, Australia and throughout the United States, Kraft has collected blood and saliva samples for genetic studies from more than 1,800 people who stutter, including more than 250 families with three generations of stuttering.

But while that effort, called the International Stuttering Project (www.theinternationalstutteringproject.com), identified new genetic variations, or variants, associated with developmental stuttering, it was not sufficiently "powered" to reveal the complexity of the condition. There simply were not enough people in the studies.

That's where Below comes in. She utilized a key VUMC resource, BioVU, one of the world's largest repositories of human DNA linked to searchable, electronic health information. BioVU has enabled researchers to conduct GWAS, or genome-wide association studies to probe the genetic underpinnings of a wide range of diseases.

Stuttering, however, is a condition that is rarely mentioned or given a diagnostic code in the medical record. People aren't hospitalized for stuttering. "We had to come up with some clever new ways to try to capture that missing code," Below said.

From confirmed cases of developmental stuttering, the researchers constructed a "constellation" of diagnostic codes for other conditions such as attention-deficit hyperactivity disorder (ADHD) and autoimmune reactions to infections that co-occur with stuttering more frequently than would be expected by chance.

Then, using machine learning techniques, they created an artificial intelligence tool that used the presence of these "phenotypes" recorded in the electronic health record to predict those who were likely to stutter, "even in the absence of having a direct note about their stuttering in their medical record," Below said.

Supported by $3.5 million, five-year grant awarded in 2018 by the National Institute on Deafness and Other Communication Disorders, part of the National Institutes of Health, the researchers demonstrated that their stuttering prediction model positively predicted the presence of stuttering more than 80% of the time.

The research also turned up a stuttering-related gene implicated in autism-spectrum disorder, as well as genetic variants that affect the regulation of sex hormones. The latter finding may help explain why boys are more likely to stutter, and why women who stutter are more likely to recover.

Some correlations between traits may be spurious, Below noted. But if the researchers establish genetic connections between stuttering and other traits such as ADHD, those findings could open up avenues for treating both conditions at the same time, Kraft said.

Researchers from private speech clinics in Dublin, Ireland, Curtin University in Perth, Australia, and the University of North Carolina at Chapel Hill contributed to the research. The National Stuttering Association, Irish Stammering Association and other organizations have supported the research by sponsoring collections.

VUMC co-authors were Hannah Polikowsky, Douglas Shaw, Dillon Pruett, Hung-Hsin Chen, PhD, MS, Lauren Petty, and Robin Jones, PhD, associate professor of Hearing and Speech Sciences. Co-authors from Curtin University included Janet Beilby, PhD, and Kathryn Viljoen.

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VUMC: Gene Discoveries Give New Hope To People Who Stutter - Cannon Courier

Introduction

In addition to its high lethality, stroke is also recognized as a vital contributor to disability and cognitive impairment.1,2 Among them, cognitive impairment significantly delays functional recovery and affects the life quality of patients,35 as well as increases healthcare costs. Therefore, early and accurate identification of risk factors associated with cognitive impairment to improve the prediction of PSCI is critical for optimizing the treatments.

Serum homocysteine, as a kind of sulfur-containing amino acids, is identified as a reactive vascular injury amino acid due to the strong oxidative effects on vascular endothelial cells and subsequent vascular lesions.6 Meanwhile, serum Hcy levels are affected by several factors, including age, sex (male), pregnancy, high methionine-rich protein diet, vitamin (such as folic acid, vitamin B6, and B12) deficiency, renal failure,7,8 genetic mutation including heterozygous/homozygous cystathionine- synthase (CBS) gene and MTHFR gene, medication (such as methotrexate and niacin) use, and so on,9,10 all of which can contribute to HHcy. As a risk factor for cardiovascular diseases, Hcy is also closely related to multiple neurological diseases such as stroke and cognitive decline.11,12 In recent years, emerging evidence has been discovered to support the link between homocysteine and PSCI,13,14 among which inflammatory pathway is regarded as one of the essential underlying mechanisms. As an acute-phase protein and the most sensitive biomarker of nonspecific inflammatory response, hsCRP is elevated in patients with cognitive impairment,15,16 and can independently predict PSCI,17 thus exhibiting the potential for evaluating cognitive disorders in clinics.18

To our knowledge, no individual study has analyzed the relationships among homocysteine, hsCRP and PSCI. In this study, we aim to investigate their relationship based on CNSR-III in patients with AIS and TIA.

We obtained the data from the Impairment of Cognition and Sleep (ICONS) subgroup of CNSR-III.19 The ICONS study is a multicenter (40 hospitals) prospective registry. It recruited AIS or TIA inpatients (within 7 days of onset) between August 15, 2015 and January 2018, with 1-year follow-up finished in March 2019 and 2625 patients were included. Patients who met the preplanned inclusion criteria were eligible: age over 18 years old; in-hospital AIS or TIA without any history of severe cognitive impairment prior to stroke or any comorbidity that could interfere with cognitive assessment. After excluding 825 individuals with missing information on Hcy,84 individuals with missing information on hsCRP at baseline and 250 individuals without MoCA assessments at 3-month follow-up, we finally included 1466 subjects for subsequent analysis (Figure 1).

Figure 1 Patient Flowchart.

Prior to data collection, we have obtained approval from the ethics committee of Beijing Tiantan Hospital, and signed informed consent from all included patients.

Patients with AIS or TIA with complete data of baseline Hcy and hsCRP levels as well as cognitive evaluation at 3-month by trained neurologists were included. Other baseline characteristics including age, gender, body mass index (BMI) as well as past history were collected by a professional physician during the interview. We dichotomized the levels of Hcy and hsCRP as follows, normal Hcy (<15 mmol/L), HHcy (15 mmol/L),20 normal hsCRP (<3 mg/L), and high hsCRP (3 mg/L).21

The MoCA was employed to detect PSCI and assess global cognition.22 Specifically, a patient with a MoCA score below 26, or less than 12 years of education and a MOCA score below 25 was considered cognitively impaired.23 The primary outcome was the prevalence of PSCI at 3 months after the onset of AIS or TIA.

The data analyses were conducted using SAS 9.4 (SAS Institute Inc, Cary, NC). Continuous variables were exhibited as medians with interquartile ranges and categorical variables as percentages. For comparisons, we used one-way analysis of variance or KruskalWallis test for the continuous variables and chi-square statistics for the categorical variables. We employed multivariable logistic regression analysis to evaluate the correlations among hsCRP, Hcy, and PSCI. Results were reported as odds ratios (ORs) with 95% confidence interval (95% CI). P < 0.05 was considered statistically significant.

We selected 1466 eligible patients from the 2625 patients in the ICONS study with a median age of 62 years old. Four hundred and fourteen (28.24%) of them were female. Compared with patients excluded, the included patients had higher rates of history of hyperlipidemia but lower BMI, as shown in Table 1.

Table 1 Baseline Characteristics of Patients Included versus Not Include

Baseline characteristics of study patients are displayed in Table 2. Among participants included in our study, 466 (31.79%) patients had higher hsCRP levels. Compared with the NCRP (normal high-sensitivity C-reactive protein) group, more patients in the HCRP (high high-sensitivity C-reactive protein) group had elevated Hcy levels. The median Hcy levels were 16.5 mol/L (NCRP group) and 16.6 mol/L (HCRP groups), respectively. Participants in the HCRP groups were older, more likely to have higher proportions of history of hypertension and diabetes, had higher systolic blood pressure at admission, furthermore, they had higher baseline white blood cell (WBC) counts and Vitamin B12 levels. While, in the HHcy group, patients with increased hsCRP concentrations were older, had higher WBC counts, folate, and vitamin B12 levels, as well as higher baseline NIHSS. While in the NHcy group, patients with increased hsCRP concentrations were older, more likely to have higher proportions of history of hypertension and diabetes, had higher baseline WBC counts and NIHSS score.

Table 2 Baseline Characteristics of Participants Stratified by Hcy and HsCRP Levels

Table 3 exhibits the comparison of outcomes between the groups. No significant differences of the PSCI were found between the NCRP and HCRP groups after adjusting for potential variables (crude OR: 1.54,95% CI: 1.231.92, p < 0.001; adjusted OR: 1.27, 95% CI: 0.991.62, p = 0.06). In the HHcy group, patients with high hsCRP level were significantly likely to suffer from cognitive impairment, even if the confounding factors were controlled (crude OR: 1.71,95% CI: 1.292.27, p < 0.01; adjusted OR: 1.42, 95% CI: 1.041.93, p = 0.03). However, no similar correlation in the NHcy group was identified (crude OR: 1.30, 95% CI: 0.911.87, p = 0.15; adjusted OR: 1.05, 95% CI: 0.701.58, p = 0.80). When comparing the four groups directly, only the high hsCRP and high homocysteine groups were related to cognitive impairment, but this association was attenuated after adjustment for potential confounders (crude OR: 1.48, 95% CI: 1.092.01, p = 0.01; adjusted OR: 1.23, 95% CI: 0.881.72, p = 0.23). Furthermore, after classifying patients according to age, sex, and TOAST criteria, those who were older (adjusted OR: 1.45, 95% CI: 1.022.05, p = 0.04), male (adjusted OR: 1.67, 95% CI: 1.052.65, p = 0.03), or large-artery atherosclerosis (LAA) classification (adjusted OR: 1.96, 95% CI: 1.053.66, p = 0.04) were more likely to have cognitive impairment if presenting high homocysteine and high hsCRP levels at the same time (Table 4). Of note, no significant interaction for the impact on PSCI was observed in subgroups stratified by age, sex, or TOAST classification (P interaction=0.9537,0.6288 and 0.8233 respectively).

Table 3 Multivariate-Adjusted Odd Ratios (ORs) for Cognitive Impairment According to hsCRP Levels and HCY at 3 Month

Table 4 Multivariable Adjusted Odd Ratios (OR) of Subgroup Analysis for Cognitive Impairment According to hsCRP Levels

Significantly increased risk of cognitive impairment was only found in patients with both elevated hsCRP and Hcy levels in our study. The associations among inflammation, homocysteine, and cognitive impairment were significant in patients who were male, older (over 65 years), and those with the TOAST classification of LAA type. For each MoCA subgroup, no significant interaction for the impact on PSCI was observed in subgroups stratified by age, sex, or TOAST classification.

Previous reports indicated hyperhomocysteinemia as a unique risk factor for cognitive impairment,24,25 Sachdev et al in 2003 found that high Hcy level was associated with cognitive impairment, especially in frontal executive functions. In 2019, a prospective multi-center registry conducted by Zhu et al showed that a risk model based on combined tHcy, rheumatoid factor (RF), and matrix metalloproteinase-9 (MMP-9) might enhance the predictive power for cognitive impairment after stroke.26 Furthermore, an observational study discovered that homocysteine level was correlated with cerebral microbleeds (CMBs) in cognitively impaired patients.27 Moreover, a research conducted in 2013 found that hsCRP combined with Hcy could predict the prognosis of AIS patients among the Chinese mainland populations.28

High concentrations of homocysteine can directly exert toxic effects on neurons, which may be caused through amino acid-induced toxicity, reactive oxidative stress (ROS), endoplasmic reticulum, and N-methyl-D-aspartate receptor (NMDAr)-mediated neurotoxicity, leading to neuronal death.2932 In addition, homocysteine may cause vascular endothelial function damage and alter permeability of bloodbrain barrier, resulting in cerebral small vessel disease. Combined with the above findings, we speculate that Hcy induces cognitive dysfunction through direct effects on glutamatergic neurotransmission and endothelin, indirect inhibition of methylation processes, enhancement of amyloid neurotoxicity, and promotion of tau phosphorylation.33 In addition, previous studies have found that endothelial inflammation under high Hcy conditions promoted vascular injury,34 which in turn led to cognitive impairment. However, the underlying mechanisms remain obscure. On the one hand, Hcy can stimulate CRP expression through ROS and mitogen activated protein kinase (MAPK) signaling pathways,35 which in turn activates NF-B and further promotes inflammation in rat vascular smooth muscle cells.36 On the other hand, homocysteine also enhances the expression of NMDAr,35 thus stimulating CRP production and triggering inflammatory responses.37 Finally, Hcy has been shown to promote neuroinflammation and microglia activation through STAT3 activation subsequent to the ischemic stroke.38 Meanwhile, it has been reported that chronic mild hyperhomocysteinemia could cause damage on nuclear acids and protein, as well as ultrastructural alterations in the cerebral cortex in an inflammation-dependent manner.39

In subgroup analysis, for patients with both high homocysteine and hsCRP levels, those who were older, male, with a TOAST classification of atherosclerosis type had a higher risk of cognitive impairment compared to those with normal hsCRP levels. Age independently influences MoCA score,3 and high age generally reflects a high level of chronic inflammation in the body because CRP level increases with age.40 Moreover, female stroke patients seem to have a worse clinical outcome due to distinct hormone levels.41,42 In addition, homocysteine is an independent risk factor for atherosclerosis,43 which may be attributed to increased collagen synthesis, oxidative damage, endothelial dysfunction, and degradation of elastic material. Meanwhile, CRP is directly involved in the progression of atherosclerosis, a typical chronic inflammatory disease,44,45 by participating in multiple inflammatory processes.46 In light of the above findings, we examined a stratified analysis of age, sex, and TOAST classification in this study, but no interactions were found.

There are several limitations in our study. First, part of the patients in this study experienced a more than 24 h time period from onset to admission, and thus, their CRP and Hcy levels on admission could not accurately reflect the authentic situation at the time of stroke. Secondly, we only obtained baseline Hcy and CRP levels without any follow-up measures, which made it impossible to study the association between changes in hsCRP and Hcy and cognitive impairment. Thirdly, we stratified the patients into groups according to the hsCRP and Hcy level and make comparisons of clinical characteristics between groups, which will cause the problem of increased type 1 error by multiple comparison. Fourthly, genetic analysis was not included in this study, while MTHFRTT homozygote for homocysteine genotype was confirmed to be related to the increased homocysteine level.27 Finally, bias existed when selecting hospitalized patients. Some older patients with other serious diseases may refuse admission at an early stage, and they may have higher levels of both homocysteine and inflammation.

Our study shows that in patients with hyperhomocysteine post AIS and TIA, high hsCRP concentrations increase the risk of cognitive impairment.

Hcy, homocysteine; hsCRP, high sensitive C-reaction protein; AIS, acute ischemic stroke; TIA, transient ischemic attack; PSCI, post-stroke cognitive impairment; ICONS, Impairment of Cognition and Sleep; CNSR-3, China National Stroke Registry-3; MoCA, Montreal Cognitive Assessment; NIHSS: National Institutes of Health Stroke Scale; mRS, modified Rankin Scale; TOAST: Trial of Org 10172 in Acute Stroke Treatment, LAA, large artery atherosclerosis, CE: Cardioembolism; SAA: small-artery occlusion; BMI, body mass index; SBP, systolic blood pressure; IQR, interquartile range; OR, odds ratio; CI, confidence interval.

Data are available on reasonable request.

This study was approved by the medical Ethics Committee of Beijing Tiantan Hospital (No.: KY2015-001- 01). All the study participants provided informed consent to take part in this study, in accordance with the Declaration of Helsinki.

We thank all study participants, of the survey teams at participating hospitals of the Third China National Stroke Registry, and the project development and management teams at the Beijing Tiantan Hospital.

All authors contributed to data analysis, drafting or revising the article, have agreed on the journal to which the article will be submitted, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

This work was supported by grants from National Key R&D Program of China (2016YFC0901002), grants from the National Natural Science Foundation of China (81870905, U20A20358).

The authors report no conflicts of interest in this work.

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Relationship among Homocysteine, Inflammation in AIS | NDT - Dove Medical Press

Experimental compound, which has received orphan drug and pediatric rare disease designations from the FDA, displays effectiveness in treating symptoms of Autism and Alzheimers disease.

An extensive international study led by Tel Aviv University found that an experimental drug which has been awarded orphan drug designation by the FDA for future treatment of a rare development disorder can also treat a variety of symptoms relating to autism, intellectual disability, and Alzheimers disease.

The experimental drug, NAP, was discovered in the lab of Prof. Illana Gozes of the Tel Aviv University Sackler Medical Schools Department of Human Molecular Genetics and Biochemistry. In recent years, the FDA has granted the experimental drug with orphan drug designation and pediatric rare disease designation for treatment of a rare developmental disorder called ADNP syndrome, which can cause a variety of symptoms, among them, hallmark features are intellectual disability and autism spectrum disorder.

In the current study, a team of researchers led by Prof. Gozes developed an innovative lab model and found that NAP can be effective in treating a broad spectrum of symptoms of ADNP syndrome, which is caused by mutations in the ADNP gene which is essential to cerebral development and protecting cerebral brain cells. Previous studies showed that ADNP syndrome is related to Alzheimers disease and certain types of mental disabilities, developmental delays, and autism.

Prof. Illana Gozes. Credit: Jonathan Blum, Tel Aviv University

Ramot, Tel Aviv Universitys technology commerce company filed a number of patent applications to protect the technology and its implementation and, in collaboration with Prof. Gozes, is raising funds to finance further clinical research. Similarly, Ramot is in discussions regarding commercial collaboration with pharmaceutical companies. Were excited by this new discovery and believe that this is groundbreaking technology that will remedy a variety of symptoms and disabilities in a broad spectrum of orphan diseases, said Prof. Keren Primor Cohen, CEO of Ramot.

The study, which is the culmination of the MD/PhD student Dr. Gideon Carmons doctoral research, was joined by a team of researchers from Prof. Gozess lab: Dr. Shlomo Sergovich, Gal Hacohen-Kleiman, Inbar Ben-Horin-Hazak, Dr. Oxana Kapitansky, Alexandra Lubincheva, and Dr. Eliezer Giladi. The team was further joined by Dr. Moran Rubinstein, Prof. Noam Shomron, and Guy Shapira of TAUs Sackler Faculty of Medicine, and Dr. Metsada Pasmanik Chor of Tel Aviv Universitys George S. Wise Faculty of Life Sciences. Researchers from the Czech Republic, Greece, Germany, and Canada also participated. The article was published in the prestigious journal Biological Psychiatry.

Prof. Gozes explained that: NAP, in fact, comprises a short segment of the normal ADNP protein. We previously found that treatment using NAP corrects the function of human nerve cells afflicted with ADNP syndrome in a laboratory test-tube. In this study, we sought to examine the efficacy of NAP in treating various aspects of the syndrome using a model with the most harmful mutation, which allowed us to view brain development and facilitate remedying of behavioral problems.

The study, which examined a model using mice with ADNP syndrome, used objective methods to analyze behavior, electrical activity, and to further identify select protein contents in the brain. The researchers found that the mice suffering from ADNP syndrome demonstrated a broad spectrum of pathological outcomes, including increased rates of neonatal death immediately after birth, slowed development and aberrant gait, primarily among females, as well as poor voice communication.

Cerebral examinations demonstrated additional findings: A relatively small number of synapses the points of contact tween nerve cells, impaired electrophysiological activity demonstrating a low potential for normal cerebral arousal, as well as precipitates (aggregates) of the Tau protein in young mice, similar to those in the brains of elderly Alzheimers disease patients.

For most of these symptoms, the researchers examined the effect of the future medicinal substance NAP made of a short and normal segment of the ADNP protein, the same protein that is impaired because of the mutation. Prof. Gozes: In the past, we have found that NAP corrects impaired functioning of ADNP that has mutated in the nerve cell model in the culture. We now examined its effect in vivo in animals modeling the syndrome (ADNP mutation). To our amazement and joy, we discovered that treatment using NAP normalizes the functioning of these mice for most of the symptoms indicated above!

Researchers further sought to identify in the blood of the mice, a clear biological indicator of ADNP syndrome that will enable diagnosis of this severe disease and effective monitoring of treatment using a simple blood test. With the help of genetic sequencing technologies, they identified an anomaly in a manner characteristic only of females as well as a method for repair using NAP on five proteins (at the messenger RNA level). These findings matched the changes discovered in white blood cells of children suffering from ADNP syndrome. One of the indicators discovered is FOXO3 a protein with an important role in generating cerebral synapses and healthy aging.

Prof. Gozes summarized: In this study, we examined the effect of the ADNP genes most prevalent mutation in a broad spectrum of aspects and found extensive impairment in physical and cerebral functioning parallel to the symptoms of autism, developmental delay, mental disability, and Alzheimers disease in humans. Similarly, we examined the potential use of the NAP drug for treating these diseases, and discovered that it is effective against most of these symptoms in lab models. This study is an important milestone on the way to developing a drug, or drugs, that will help children with autism stemming from genetic mutations, as well as Alzheimers patients.

Reference: Novel ADNP Syndrome Mice Reveal Dramatic Sex-Specific Peripheral Gene Expression With Brain Synaptic and Tau Pathologies by Gidon Karmon, Shlomo Sragovich, Gal Hacohen-Kleiman, R. Anne McKinney, Moran Rubinstein and Illana Gozes, 27 September 2021, Biological Psychiatry.DOI: 10.1016/j.biopsych.2021.09.018

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Groundbreaking Experimental Compound Displays Effectiveness in Treating Symptoms of Autism and Alzheimers Disease - SciTechDaily

90 Day Fianc: Before the 90 Daysreturned with a new season on Dec. 12, 2021, with seven new couples for fans to watch. The cast of season 5 also includes the first little person Alina to appear within the90 DayFiancfranchise. Twenty-seven-year-old Alina lives in St. Petersburg, Russia, but her boyfriend, Caleb, is American.Before the 90 Dayswill show the ups and downs of their relationship as they navigate the waters of international dating.

Besides being the first little person to appear on 90 Day Fianc: Before the 90 Days, Alina also has a different story about how she and Caleb met. Most couples onBefore the 90 Daysmeet through international dating sites as they actively search for love. Alina and Caleb met when they were just teenagers. Caleb wanted to meet some potential friends before leaving for an extended trip to Russia. Thats when he and Alina connected in an international chatroom.

However, the meeting never materialized, but the two connected several years later. Now, theyve discovered they want something deeper than a friendship, so both of them will travel to Turkey to finally meet in person.

RELATED: 90 Day Fianc: Before the 90 Days Season 5 Couples: Who Are Gino and Jasmine?

In theBefore the 90 DaysSeason 5 premiere episode, Alina talks about her medical condition known as Diastrophic Dysplasia.

Alina explains, Its a form of dwarfism. Its rare and it affects everyone differently. For a child to be born with this type of dwarfism both parents have to be carriers of the gene. It can affect your joints and, of course, your stature. My hands and my feet look pretty different too, but I dont think the disability is a problem. In many areas of my life, I try to do everything, really.

According toJohn Hopkins Medicine, Diastrophic dysplasia can affect the development of body parts including the hands, face, ears, feet, hips, legs and spine. People with diastrophic dysplasia are generally shorter than average in height.

Just like the condition affects everyone in different ways, doctors use different treatment methods depending on the symptoms the person exhibits.

However, Alina doesnt let the disorder hold her back. Im pretty comfortable in my body. Ive already accepted the fact that I dont look like everyone else and Im just trying to rock what I have. But there are things that are hard to do. With my hands, its a bit hard to do some things because my fingers dont really bend. I cant walk a lot. So, I use a wheelchair for longer distances, she explains inBefore the 90 Days.

RELATED: 90 Day Fianc: Before the 90 Days Season 5: Fans Accuse Ella of Fetishizing Asian Culture

In theBefore the 90 DaysSeason 5 Episode 1, Alina explains that her parents often baby her and her sister. However, due to her disorder, she gets the brunt of the worry from her parents. Neither are thrilled Alina is traveling to Turkey to meet a man shes never met in person before. However, she explains her friend Elijah plans to accompany her to help her with anything she might need.

It looks like Alina and Caleb finally meet in person inBefore the 90 DaysSeason 5 Episode 2. The show airs on Sunday nights at 8 P.M. ET and streams on discovery+.

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'90 Day Fianc: Before the 90 Days': Everything to Know About Alina's Rare Medical Condition Diastrophic Dysplasia - Showbiz Cheat Sheet

The joint venture will include a new clinical laboratory, which is expected to encompass 40,000 s.f. and house three dozen sterile clean rooms.

COVINGTON, Ky. Cincinnati Childrens Hospital Medical Center and the research service provider CTI Clinical Trial & Consulting Services in Covington have agreed to form a company that will focus on providing cell and gene therapy manufacturing services to the biotechnology and pharmaceutical industries.

Medicine is rapidly evolving toward cell- and gene-based therapies, said Dr. Steve Davis, president and CEO of Cincinnati Childrens. By melding the scientific expertise of Cincinnati Childrens with the operational expertise of CTI, this joint venture will ensure that our community, region and the world have ready access to the most innovative and effective therapies.

Tim Schroeder, CEO and chairman of CTI, said: We anticipate advances in cell and gene therapies to bring about medical breakthroughs with the potential to not only treat, but actually cure some rare and complex diseases including some forms of cancer.

The joint venture will enable Cincinnati Childrens to expand on the work of its existing Translational Core Laboratory, which manufactures and tests services for cell and gene therapy clinical trials, said Hector Wong, MD, vice chair of the Department of Pediatrics at the medical center.

There is a global shortage of manufacturing capacity, which has begun to impede development of new cell and gene therapies. The industry has less than 1% of the capacity needed to support a growing volume of clinical programs, according to CTI. Fifteen cell and gene therapy products have been approved by global regulatory agencies, and the Alliance for Regenerative Medicine estimates 10 to 20 additional approvals per year by 2025.

CTI and Cincinnati Childrens have been engaging in conversations for some time about ways to further these developments and bring new treatments to the children and adult patients looking for hope, Schroeder said. This joint venture is a natural evolution of our pre-existing relationship involving clinical trials, maximizing the expertise and resources of both organizations to collaborate, innovate, and facilitate scientific developments with the potential to save lives.

The approximately $100 million investment in the joint venture will include a new clinical laboratory, which is expected to encompass 40,000 s.f. and house three dozen sterile clean rooms. The facility will have the potential to support the research of more than 30 clinical trial sponsors at a time. The specific location has yet to be determined, but the facility will be in the Cincinnati/Northern Kentucky region. The opening date is expected to be 2023.

The joint venture will ensure that Cincinnati Childrens faculty and researchers have access to a state-of-the-art, multimodal cell and gene therapy manufacturing laboratory, which is expected to help retain and draw the best talent in the world to the medical center, Wong said. The facility will enhance Cincinnati Childrens ability to participate in early phase cell and gene therapy research and clinical trials, leading to improved treatments and, hopefully, cures.

About 150 jobs are to be created by the joint venture, and the new company will build on the regions growing status as a research hub.

CTI Clinical Trial and Consulting Services is a global, privately held, full-service contract research organization (CRO), delivering a complete spectrum of clinical trial and consulting services throughout the lifecycle of development, from concept to commercialization. CTIs focused therapeutic approach provides pharmaceutical, biotechnology, and medical device firms with clinical and disease area expertise in rare diseases, regenerative medicine/gene therapy, immunology, transplantation, nephrology, hematology/oncology, neurology, infectious diseases, hepatology, cardiopulmonary, and pediatric populations. CTI is currently part of more than 30 active COVID-19 projects for treatment and prevention. It also offers a fully integrated multi-specialty clinical research site, as well as complete global laboratory services. Now in its third decade, it is one of the 20 largest CROs in the world with associates in more than 60 countries across six continents.

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Cincinnati Children's teams up with CTI on cell and gene therapies - The Lane Report

With the emergence of genetic sequencing, advances in diagnostics and wearable devices, there has been a swell of excitement around precision medicine or customised healthcare. The story in itself has fuelled a billion dollar market for public consumption. However, the industry is outpacing the science, and as yet, it is not so straight forward.

I have compiled a list of some of the key areas and advances in personalised medicine, which we will see come in to focus over the next few years:

1. Hormones: Such as oestrogen, progesterone, testosterone and thyroid, to name but a few. As physicians, we have been fortunate enough to tailor the needs to the individual, depending on the patients blood results and their symptoms. Although this is not new, treatments can vary, based on conventional wisdom, body-identical, bio-identical and natural supplements. It can be difficult for patients to navigate, as some practitioners have become more like alchemists, trialing different treatments (by their very nature it is not always evidence-based). For more detail please read my articles on correcting hormonal imbalance.

2. Cancer risk and diagnosis: Home DNA genetic test-kits have made checking for inheritable diseases widely available, but with some controversy (I have elaborated on this in my other article). They have also discovered new techniques for identifying cancer cell DNA markers in the blood, also known as liquid biopsies. This could potentially pick up of over 50 early stage cancers. Current trials are underway in the US and UK, which could lead to a paradigm shift in early-cancer detection for individuals, the likes of which we have not seen for over 30 years. Using polygenic risk scores (different combinations of genetic variance for a particular disease), multiple data points can be stacked for each individual (i.e. demographics/family history etc) and offer greater diagnostic precision.

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Is 'personalised medicine' the future of healthcare? - Tatler

National Health Institute Director Francis S. Collins served for 12 years under three presidents and presided over an expansion of the agency's budget and efforts to develop new cures to diseases. Graeme Jennings/POOL/AFP via Getty Images hide caption

National Health Institute Director Francis S. Collins served for 12 years under three presidents and presided over an expansion of the agency's budget and efforts to develop new cures to diseases.

It's Dr. Francis Collins' last few weeks as director of National Institutes of Health after 12 years, serving three presidents. Collins made his name doing the kind of biomedical research NIH is famous for, especially running The Human Genome Project, which fully sequenced the human genetic code. The focus on biomedicine and cures has helped him grow the agency's budget to over $40 billion a year and win allies in both political parties.

Still, in a broad sense, Americans' health hasn't improved much in those 12 years, especially compared to people in peer countries, and some have argued the agency hasn't done enough to try to turn these trends around. One recently retired NIH division director has quipped that one way to increase funding for this line of research would be if "out of every $100 dollars, $1 would be put into the 'Hey, how come nobody's healthy?' fund."

In a wide-ranging conversation, Collins answers NPR's questions as to why for all the taxpayer dollars going to NIH research there haven't been more gains when it comes to Americans' overall health. He also talks about how tribalism in American culture has fueled vaccine hesitancy, and he advises his successor on how to persevere on research of politically charged topics like guns and obesity and maternal health even if powerful lobbies might want that research not to get done.

This interview has been edited for length and clarity.

Selena Simmons-Duffin: After you announced you'd be stepping down from the director role, you told the New York Times that one of your "chief regrets" was the persistence of vaccine hesitancy during the pandemic. How are you thinking about the role NIH could play in understanding this problem?

Francis Collins: I do think we need to understand better how in the current climate people make decisions. I don't think I anticipated the degree to which the tribalism of our current society would actually interfere with abilities to size up medical information and make the kinds of decisions that were going to help people.

To have now 60 million people still holding off of taking advantage of life saving vaccines is pretty unexpected. It does make me, at least, realize, boy, there are things about human behavior that I don't think we had invested enough into understanding. We basically have seen accurate medical information overtaken, all too often, by the inaccurate conspiracies and false information on social media. It's a whole other world out there. We used to think that if knowledge was made available from credible sources, it would win the day. That's not happening now.

So you mentioned the idea of investing more in the behavioral research side of things. Do you think that should happen?

We're having serious conversations right now about whether this ought to be a special initiative at NIH to put more research into health communications and how best to frame those [messages] so that they reach people who may otherwise be influenced by information that's simply not based on evidence. Because I don't think you could look at the current circumstance now and say it's gone very well.

Looking at how America has fared in the pandemic more broadly, it really is astoundingly bad. The cases and deaths are just so high. CDC Director Robert Redfield, when he was leaving, told NPR he thought the baseline poor health of Americans had something to do with how powerfully the pandemic has hit America. What do you think about the toll of the pandemic, even as it's clearly not over?

It's a terrible toll. We've lost almost 800,000 lives. In 2020, before we had vaccines, there was not a really good strategy to protect people other than social distancing and mask-wearing, which were important, but certainly not guarantees of safety. And yes, it is the case that the people who got hit hardest, oftentimes, were people with underlying medical conditions.

But in 2021, we should have been better off. We had vaccines that were safe, that were available for free to all Americans. The ability to get immunized really went up very steeply in March and April, and yet it all kind of petered out by about May or June. The [vaccine] resistant group of 60 million people remains, for the most part, still resistant. Unfortunately, now, with delta having come along as a very contagious variant and with omicron now appearing, which may also be a real threat, we have missed the chance to put ourselves in a much better place.

Let's step back from the pandemic. In your 12 years as director, the NIH has worked on developing cures and getting them from the lab to patients faster, and the agency's budget has grown.

But, in that time, Americans haven't, on a broader scale, gotten healthier. They're sicker than people in other countries across the board, all races and incomes. When you were sworn in in 2009, life expectancy was 78.4 years, and it's been essentially stuck there.

Does it bother you that there haven't been more gains? And what role should NIH play in understanding these trends and trying to turn them around?

Well, sure, it does bother me. In many ways, the 28 years I have been at NIH have just been an amazing ride of discoveries upon discoveries. But you're right, we haven't seen that translate necessarily into advances.

Let's be clear, there are some things that have happened that are pretty exciting. Cancer deaths are dropping every year by one or two percent. When you add that up over 20 years, cancer deaths are down by almost 25% from where they were at the turn of the century. And that's a consequence of all the hard work that's gone into developing therapeutics based on genomics, as well as immunotherapy that's made a big dent in an otherwise terrible disease.

But we've lost ground in other areas, and a lot of them are a function of the fact that we don't have a very healthy lifestyle in our nation. Particularly with obesity and diabetes, those risk factors have been getting worse instead of better. We haven't, apparently, come up with strategies to turn that around.

On top of that, the other main reason for seeing a drop in life expectancy other than obesity and COVID is the opioid crisis. We at NIH are working as fast and as hard as we can to address that by trying to both identify better ways to prevent and treat drug addiction, but also to come up with treatments for chronic pain that are not addictive. Because those 25 million people who suffer from chronic pain every day deserve something better than a drug that is going to be harmful.

In all of these instances, as a research enterprise because that's our mandate it feels like we're making great progress. But the implementation of those findings runs up against a whole lot of obstacles, in terms of the way in which our society operates, in terms of the fact that our health care system is clearly full of disparities, full of racial inequities. We're not at NIH able to reach out and fix that, but we can sure shine a bright light on it and we can try to come up with pilot interventions to see what would help.

A 300-page report called "Shorter Lives, Poorer Health" came out in 2013 it was requested and financed by NIH and conducted by a National Academies of Science, Engineering and Medicine panel. It documented some of the things you just talked about, in terms of how Americans' health falls short compared to other countries. And it is filled with recommendations for further research, many specifically for NIH, including looking to how other countries are achieving better health outcomes than the U.S.

I'm curious, since this report came out when you were director, if it made an impact at the agency and whether there's been any progress on those recommendations or was a decision not to pursue those ideas?

I do remember that report and there have been a lot of other reports along the lines since then that have tried to point to things that other countries may be doing better than we are. One of the things I've tried to do is to provide additional strength and resources to our Office of Disease Prevention, because that's a lot of what we're talking about here. One of the knocks against the National Institutes of Health is that we often seem to be the National Institutes of Disease that a lot of the focus has been on people who are already diagnosed with some kind of health condition. And yet what we really want to do is to extend health span, not just lifespan, and that means really putting more research efforts into prevention.

One of the things that I'm excited about in that regard is the All of Us study, which is in the process of enrolling a million Americans, following them prospectively, many of them currently healthy. They share their electronic health records, they have blood samples taken that measure all kinds of things, including their complete genome sequences; they answer all kinds of questionnaires, they walk around with various kinds of wearable sensors. That's going to be a database that gives us information about exactly what's happened to the health of our nation and what could we do about it.

You've served under both Democratic and Republican administrations. One thing you've talked about in interviews is the culture wars. What role do you think NIH has to play in terms of developing trust and trying to get past some of that tribalism that you talked about before?

I think medical research should never be partisan. It should never get caught up in culture wars or tribal disagreements. But in our current society, it's hard to think of anything that hasn't at least been touched by those attitudes.

My goal as NIH director over these 12 years, serving three presidents, was to always try to keep medical research in a place that everybody could look at objectively and not consider it to be tainted in some way by political spin. I've made friends in Congress in both parties and both houses, in a way that I think has really helped the view of medical research to remain above the fray. And many of the strongest supporters for medical research over these 12 years have been in the Republican Party.

This is not something that people can really disagree about. You want to find answers to medical problems that are threatening yourself or your family or your community or your constituents. So I don't have a hard job in terms of explaining the mission or why we work so hard at what we do.

But I do have to sometimes worry that for whatever reason, politics will creep into this. And certainly with COVID, politics has crept into the space of misinformation in a fashion that has not helped with vaccine hesitancy. Frankly, I think it's pretty shameful if political figures trying to score points or draw attention to themselves put forward information about COVID that's demonstrably false.

Some of the reasons why Americans tend to be less healthy than people in other countries can get political pretty quickly like healthy environments and gun injuries and drug overdoses and maternal health. But the research is important.

Do you have any guidance or thoughts for your successor on how to support the kind of research that's not as universally embraced on both sides of the aisle?

I think the guidance is you have to look at all the reasons why people are not having a full life experience of health and figure out what we, as the largest supporter of medical research in the world, should be doing to try to understand and change those circumstances. A lot of this falls into the category of health disparities. It is shameful that your likelihood of having a certain lifespan depends heavily on the zip code where you were born, and that is a reflection of all of the inequities that exist in our society in terms of environmental exposures, socioeconomics, social determinants of health, et cetera.

We are ramping up that effort right now, especially not just to observe the situation or, as some cynics have said, admire the situation. We actually want to try pilot interventions to see if some of those things can be changed. But that's about as far as we can go. Again, if there's a major societal illness right now of tribalism and over-polarization and hyper-partisanship about every issue, probably the NIH is not well positioned all by ourselves to fix that. We have an urgent need, I think, across society, to recognize that we may have lost something here our anchor to a shared sense of vision and a shared sense of agreement about what is truth.

You are leaving this post. Where do you imagine the agency might go next? I know you're still going to be doing your work on Type 2 diabetes you'll still be a part of it. So what do you see in NIH's future?

I think it is in a remarkably positive place right now as far as what we are called to do, which is to make discoveries, to learn about how life works and then apply that in a way that will lead to answers for diseases that currently don't have them. I think of NIH as not just the National Institutes of Health, but the National Institutes of Hope, and we are able now to provide hope for lots of situations that previously couldn't have really been confident in that. Look what's happened in terms of gene therapies we're curing sickle cell disease now, something I thought would never happen in my lifetime, with gene therapies. Look at what we're able to do with cancer immunotherapy, saving people who have stage IV disease, in certain circumstances, by activating the immune system. And of course, in infectious diseases not only have we now got mRNA vaccines for the terrible COVID-19 situation, we can apply those to lots of other infections as well.

So, anybody listening to this who's thinking maybe of moving into a career in biomedical research, this is the golden era and we need all the talent and the vision that we can possibly recruit into our midst because it's going to be a grand adventure in the coming decades.

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Francis Collins on medical advances, vaccine hesitancy and Americans' ill health : Shots - Health News - NPR

Global Gene Expression Analysis Market: Overview

Gene expression makes an analysis of the study of the activity or occurrence of the making of a gene product from its coding gene. This process is considered a delicate indicator of biological activity in which a change in the gene expression pattern leads to a change of biological process.

Growth in the global gene expression analysis market is basically driven by various factors such as increased availability of gene expression databases, emerging areas of genomics, and rise in the incidences of cancer worldwide. Comparison of expression levels of one or more genes from various samples is one of the most common uses of gene expression analysis. Some of the common and interesting comparisons comprise before and after treatment, Mutant versus Wild type, normal versus diseases, spatial variations inside tissues, organs, or any other sample type.

The report on the global gene expression analysis market captures a closer view of the leading changes that have taken place lately in the techniques of chemical analysis. It also provides a view of how those changes are shaping the contours of the global gene expression analysis market. These insights are forecasted to help the industry players and investors to assess the entire ecosystem and accordingly formulate strategies.

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Global Gene Expression Analysis Market: Trends and Opportunities

Declining Cost of Sequencing to Accelerate Growth of the Market

The rise in the need for personalized medicine is likely to influence the global gene expression analysis market over the timeframe of projection. Besides, increase in the funding of associated programs is estimated to fuel growth of the market over the projection period.

In addition to that, a decline in the cost of sequencing is likely to emerge as another growth promoting factor for the global gene expression analysis market. Emergence of new areas of genomics application and augmented availability of database of gene expression is estimated to support expansion of the growth of the global gene expression analysis market in the years to come.

Another significant factor that is likely to influence the growth of the global gene expression analysis market is strong emphasis on laboratory research. The drug discovery and development is another factor that is likely to offer lucrative growth opportunities for the growth of the market.

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Clinical diagnostics is see an increasing application of gene expression analysis over the tenure. The microbiological and biotechnological use of gene expression analysis is estimated to see a rise over the projection period. These factors are expected to drive the market toward growth over the assessment tenure, from 2018 to 2026.

Biotechnology and pharmaceutical companies make use of gene expression analysis products and services to meet clinical research goals like biotech research, and drug development and discovery. Biopharmaceutical companies emphasize on the invention of targeted therapies, particularly for the treatment of diseases like rare and complicated genetic disorders, cancer, and others. These factors are likely to offer lucrative opportunities of growth for the market.

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Global Gene Expression Analysis Market: Regional Outlook

In the global gene expression analysis market, North America is likely to wield its influence over the market over the tenure of assessment. Augmented focus on life science research on cancer by governments, increased focus on research and development activities, and setting up of bioresearch centers across the regions are likely to fuel regional growth. In addition to that, increased support from the government to raise the standard of healthcare facilities is expected to boost the expansion of the market in North America.

Emerging countries such as Brazil, China, and India are also forecasted to play an important role in offering promising growth opportunities for the global gene expression analysis market. Many established market players are seen to enter into collaborations with local players of the region to widen scope of the regional market in near future.

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Global Gene Expression Analysis Market: Companies Mentioned in Report

Key players mentioned in the report are Luminex Corporation, Oxford Gene Technologies, Ltd., Thermo Fisher Scientific, Inc, Agilent Technologies Inc., F. Hoffmann-La Roche Ltd., and Eurofins Scientific.

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Wearable Injectors Market:

In the presence of various new technologies that have come to the fore of healthcare sector, it is easy to popularise wearable injectors that can work in tandem with other devices and technologies. Delivery systems are an important component of treatment processes as they help in timely administration of medical doses. In light of these factors, it is safe to expect that the global wearable injectors market would tread along a lucrative pathway in the times to follow

Polymerase Chain Reaction Consumables Market:

The global polymerase chain reaction (PCR) market is primarily segmented based on type of product and end user. Based on the type of product, the global market is mainly segmented into consumables, reagents, and instruments. Among these, the segment of reagents has been the most dominant one in terms of value. This dominance of the segment is due to its high levels of consumption. This segment is expected to witness a promising CAGR in the coming years of the forecast period because of the rising innovation in the field of specificity of reagents. In addition to this, large scale availability of different types of tests which need different types of reagents, increasing geriatric population, growing prevalence of infectious diseases, and increasing demand for innovation in specificity of reagents are some of the other factors helping to drive overall growth of the reagent segment.

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Gene Expression Analysis Market: Rise in the need for personalized medicine is likely to influence the global market - BioSpace

First approval of Clinical Trial Application was received from United Kingdom Medicines & Healthcare products Regulatory Agency (MHRA)

EVRY, France, December 06, 2021--(BUSINESS WIRE)--Atamyo Therapeutics, a biotechnology company focused on the development of new-generation gene therapies targeting neuromuscular diseases, today announced the first authorization of a Clinical Trial Application (CTA) in Europe for ATA-100, its gene therapy for the treatment of the fukutin-related protein (FKRP) limb-girdle muscular dystrophy Type 2I/R9 (LGMD2I/R9). This authorization was granted by the United Kingdom Medicines & Healthcare products Regulatory Agency (MHRA). Additional CTAs were filed in France and Denmark.

"We are thrilled to obtain our first CTA approval in the U.K. for the devastating LGMD2I/R9 disease," said Dr Sophie Olivier, Chief Medical Officer of Atamyo. "Atamyo plans to initiate dosing in patients for ATA-100 in the first half of 2022".

"LGMDR9 is a severe muscular dystrophy with progressive symptoms for which there is currently no approved treatment," said Pr John Vissing, Director of the Copenhagen Neuromuscular Center at the National Hospital, Rigshospitalet (Denmark), and principal investigator of this trial. "It is a great motivation to know that the work we are doing has the potential to make a life-changing difference for the patients affected by this disease."

"We are eager to start treating the first European patient and mark this as a milestone for the field in advancing a potential one-time treatment for patients with LGMD-R9," said Pr Volker Straub, Professor of Medicine and Director of the John Walton Muscular Dystrophy Research Centre, Newcastle University (UK).

"This is an important step in our mission to bring to patients suffering from limb-girdle muscular dystrophies (LGMD) a new generation of safe and effective gene therapies, after only one year of activity," said Stphane Degove, CEO of Atamyo Therapeutics.

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LGMD2I/R9 is a rare genetic disease caused by mutations in the gene that produces fukutin-related protein (FKRP). It affects an estimated 5,000 people in the US and Europe. Symptoms appear around late childhood or early adulthood. Patients suffer from progressive muscular weakness leading to loss of ambulation. They also are prone to respiratory impairment and myocardial dysfunction. There are currently no curative treatments for LGMDR9.

ATA-100, a gene therapy candidate for LGMD21/R9, delivers a normal copy of the gene for production of FKRP proteins. The therapy is based on the research of Atamyo Chief Scientific Officer Isabelle Richard, Ph.D., Research Director at CNRS who heads the Progressive Muscular Dystrophies Laboratory at Genethon.

In preclinical mice models, ATA-100 demonstrated its tolerability and capability to correct symptoms and biomarkers of the pathology at unprecedented low doses for systemic AAV-mediated gene transfer addressing muscle diseases.

About Atamyo Therapeutics

Atamyo Therapeutics is focused on the development of a new generation of effective and safe gene therapies for neuromuscular diseases. A spin-off of gene therapy pioneer Genethon, Atamyo leverages unique expertise in AAV-based gene therapy and muscular dystrophies from the Progressive Muscular Dystrophies Laboratory at Genethon. Atamyos most advanced programs address different forms of limb-girdle muscular dystrophies (LGMD). The name of the company is derived from two words: Celtic Atao which means "Always" or "Forever" and Myo which is the Greek root for muscle. Atamyo conveys the spirit of its commitment to improve the life of patients affected by neuromuscular diseases with life-long efficient treatments. For more information visit http://www.atamyo.com

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Contacts

U.S. Contact: Charles Craig, Opus Biotech CommunicationsCharles.s.craig@gmail.com, 404-245-0591

European contact: contact@atmayo.com

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Atamyo Therapeutics Obtains First Regulatory Authorization in Europe to Initiate a Clinical Trial for ATA-100, its Gene Therapy to Treat Limb-Girdle...