Category Archives: Gene Medicine

Nov 21, 2019 08:42 AM EST

(Photo : Josh Reddekopp, Unsplash)Genetic modification is expected to free or at least delay hereditary diseases.

When you heard of the word GMO, the first thing that you will probably think of is food items you find at the grocery store that was modified by scientists to change their appearance or just improved their overall qualities.

However, a recent scientific paper claimed that the same gene-altering method might be able to apply to human embryos ethically within two years.

According to bioethicist Kevin Smith, this method will give hope to parents who want their children to be free from genetically-transmitted diseases.

He also said that from a "utilitarian standpoint", gene-altering is the only "conceivable" way of dealing with these conditions. Some conditions he mentioned are cancer, cardiovascular diseases, and dementia.

And since this practice is generally opposed by the public due to the fear of abusing it, Smith suggested simply delaying the conditions, which can still extend the disease-free lifespan of future individuals.

Yet he still believed that this method would be "ethically justified" within two years, especially since current gene-editing technologies present low risks even if used on human embryos.

The study was criticized by other health experts, mostly pointing out the insufficiency of experimentation to prove its safety.

Joyce Harper of the University College London (UCL) Institute for Women's Health said that while gene editing has used potential, she also wants public debate and lawmakers' interventions to ensure its ethicality.

The director of Progress Educational Trust (PET), Sarah Norcross, said that we should have learned the controversial genome-edited babies introduced by a Chinese scientist last year. She also mentioned the need for "higher scientific and ethical standards" if this practice will strive.

The study was published last week in the journal Bioethics.

Last year, Chinese scientist He Jiankui announced in Youtube that he had successfully created the first genetically modified babies -- twin girls that are immune to HIV -- using the gene-editing tool CRISPR-Cas9.

This resulted in an international outcry. Feng Zhang, one of the inventors of CRISPR, told CNN that nobody, including the scientific community, has expected someone to use the tool on humans. Other scientists were refusing to do this since the technology is still not quite complete and the possible genetic complications on humans in their later years are still unknown.

The Chinese authorities called He, who is also a professor at the Southern University of Science and Technology in Shenzhen, to halt his activities. Fellow Chinese scientists condemn him and called him an insult to the biochemical research in China.

Because of He's practice, the country was also scrutinized due to its previous reputation of favoring innovation too much even if it means setting aside ethical questions.

The Journal Nature Medicine recently published a study that claims genetically modifying embryos would result in a shorter lifespan.

Despite the massive backlash, He defended his project at the Second International Summit on Human Genome Editing held at Hongkong in November last year. According to him, this method had given hope to the parents of the twins, whose father is infected with HIV.

He also announced that he is working on the third genetically modified baby but no further information was given.

READ: It's in the Genes: Study Discovers 79 Forms of Genetic Obesity, More Than Previously Thought

2018 NatureWorldNews.com All rights reserved. Do not reproduce without permission.

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Genetically Modified Babies? Possible Within the Next Two Years, Scientists Claim - Nature World News

In this paper, Carmen D Herling, Department I of Internal Medicine, Center for Integrated Oncology, Aachen-Bonn-Cologne-Duesseldorf, Cologne, Germany, and colleagues hypothesized that the duration of response to FCR chemoimmunotherapy depends on differences in the expression of protein-coding genes. Therefore, they developed and validated a 17-gene expression signature to identify patients that might achieve durable remissions following front-line FCR chemoimmunotherapy.

Study design and patients1

Results1

After the gene expression data analysis for the MDACC cohort, the authors identified 1,136 probes associated with time to progression. Using these probes, patients with similar gene expression patterns were divided into favorable, intermediate, and unfavorable prognosis subsets. The intermediate prognosis and unfavorable prognosis subset had a shorter time to progression compared with patients in the favorable subset.

Genes highly expressed in unfavorable cases (n= 424) were associated with metabolic pathways, including oxidative phosphorylation and ribonucleoside metabolism. Genes highly expressed in favorable or intermediate cases (n= 401) encoded products involved in ATP binding, purine ribonucleoside triphosphate binding, nucleic acid binding, and DNA-template transcription.

The authors developed a prognostic model with 17 genes to distinguish IGHV-unmutated patients that had an intermediate outcome from those with an unfavorable outcome after front-line FCR therapy. The development process included:

These 17 genes were validated in 109 patients with an IGHV-unmutated status from the CLL8 cohort. In this cohort, patients classified as high risk (unfavorable prognosis; median time to progression of 39 months [IQR 2269]) had a hazard ratio of 1.90 (95% CI 1.183.06; P = 0.008) compared with low-risk (intermediate prognosis; median time to progression of 59 months [IQR 2884]) patients. Of the 17 genes, 13 came from the cluster of genes highly expressed in unfavorable cases with shorter time to progression, and increased expression corresponds to increased risk of progression. Three of the 17 genes came from the cluster of genes highly expressed in favorable or intermediate cases with longer time to progression and increased expression corresponds to decreased risk.

Conclusions

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A 17-gene expression signature to distinguish patients who are likely to achieve long-term remissions following front-line FCR chemoimmunotherapy from...

Researchers strive to address societal health issues through gene editing

In October, three researchers at UC Davis were awarded a $1.5 million grant to fund their project which attempts to demonstrate the effectiveness of gene editing through use of CRISPR, a powerful technology that allows alteration of DNA sequences to change gene function.

This kind of design can help enhance personalized medicine, said R. Holland Cheng, a professor of molecular and cellular biology in the College of Biological Sciences. Specific patients with specific illnesses can be treated in specific ways.

Cheng, along with Kit Lam, a distinguished professor and chair of the Department of Biochemistry and Molecular Medicine in the School of Medicine, and David Segal, a professor in the Department of Biochemistry and Molecular Medicine, were awarded this highly competitive and sought-after grant from the National Institute of Health (NIH).

UC Davis is part of the NIHs Somatic Cell Genome Editing (SCGE) consortium which has awarded grants to 45 other research institutes across the nation so they can begin groundbreaking work on gene editing. Through this consortium, the NIH hopes to find an efficient and safe way to conduct gene editing. Research programs are investigating the best delivery mechanism as well as the most dynamic gene editing tool.

The major problem with gene editing currently is the inability of cells to be edited within a living organism. It has become fairly easy and efficient to edit genes in a cell culture outside of the body but extremely difficult to do the same processes inside the body. Cheng, Lam and Segal are focused on changing this.

The question is how to do it inside of an animal and eventually a human, Lam said.

They are answering this question by utilizing Chengs work in engineering a non-toxic nanoparticle that they hope can transport the gene editing tool CRISPR into the cells of a living organism. Cheng has been able to create a Hepatitis E viral nanoparticle (HEVNP) that when manipulated could be a delivery system for CRISPR. They plan to take this nanoparticle and encase CRISPR inside of it, producing a mechanism for delivery of CRISPR.

The Hepatitis E nanoparticle has the capacity to be a highly efficient way to deliver gene editing to cells in the body due to its unique nature. HEVNP is resistant to the gastric acid environment of the intestines and stomach, enabling it to survive once its entered the body. Given its resistant abilities, HEVNP can be taken orally, making it a useful form of medicine. If able to successfully get HEVNP to the target cells in the body and deploy CRISPR, gene editing abilities could drastically change.

The addition of a cell-type specific targeting ligand to the HEVNP would code the nanoparticle to deliver CRISPR to a specific cell. The abilities of this method to be precise and safe will determine its success.

With five years of funding from the NIH, these three researchers are eager to begin work on this project and see the strides that can be made in gene editing. They have impressive goals for this research, as it has the capacity to reshape medicine.

This will redefine precision medicine as currently there is broad medicine that can cause side effects to people and not be effective, yet by making it specialized it is becoming more precise and effective, Cheng said.

As more effective and safe tools to cure illnesses are being tested and created, the benefits to society could be expansive. With so much potential to help improve the health of society, the NIH is dedicated to coming to new solutions at a quick rate. All programs that received grants will be required to share and utilize the research occurring at other funded programs. The NIH is hoping to eliminate the private nature of research through enforcing the sharing of ideas, as scientists are often constrained by the institutions they work for. It is their hope that by having communication between the programs, positive results will arise faster.

I think this is great because scientists inherently want to work with each other but have real world concerns especially with money, Segal said.

The research results, when groundbreaking, can provide incredible monetary gains and credibility to the institutions that made the discovery. Ultimately, scientists collaborating with one another will serve society as people are able to benefit earlier from this innovative research.

We want the public to know that we are working in their best interest, Segal said.

The NIH grant is competitive and still the third research program to join the consortium at UC Davis. Innovation has never been more prevalent than in this field at UC Davis. With three different programs researching gene editing, UC Davis stands out as a hotspot for this field of research.

Written by: Alma Meckler-Pacheco science@theaggie.org

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UC Davis leads in innovative gene editing research with NIH grants - The Aggie

During the process ofin vitrofertilization (IVF), it is not unusual for embryos to undergo preimplantation genetic diagnosis (PGD) identify specific inherited disease-causing mutations for single-gene disorders, like cystic fibrosis. Recently, new developments in genetics have given the ability to assign individuals "polygenic scores," which can somewhat explain the variability seen in complex human traits. This concept, applied to IVF embryos, has raised the prospect of "designer babies." However, there has been no research published to indicate the potential success of polygenic embryo selection.

"The notion that you could accurately choose your child's height or select for a higher IQ, like in the movie 'Gattaca,' has never been tested," said Dr. Lencz, professor in the Institute of Behavioral Science at the Feinstein Institutes and co-corresponding author of the Cell paper. "Through our research, we can confidently say that trait predictions for embryos based on polygenic scores are not very accurate."

Dr. Lencz and the team analyzed embryo selection for height and IQ in the context of a hypothetical IVF cycle. Investigators used three sources of data to evaluate the efficacy of trait selection, including a mathematically-derived genetic model, simulated embryo genomes, and a real dataset of nuclear families with large numbers of offspring (10 on average) who are now fully-grown adults with available genetic and trait (height) data.

The results concluded that screening for such traits using polygenic scores would leave a large margin for error. For example, children with the highest polygenic score for height were only the tallest in a quarter of families analyzed.

"Dr. Lencz's study adds important data highlighting the unreliability of trait selection by current methods of embryo genetic screening," saidKevin J. Tracey, MD,president and CEO of the Feinstein Institutes.

The ethical and legal debate surrounding polygenic embryo selection is already underway, but, until now, without a solid scientific foundation. The research team hopes that this work will promote an open and evidence-based discussion of these aspects among the public and policymakers.

Previously, an overview of this research was presented at the American Society for Human Genetics Annual Meeting in October by Dr. Lencz's co-lead, Dr. Shai Carmi of the Hebrew University of Jerusalem.

About the Feinstein Institutes The Feinstein Institutes for Medical Researchis the research arm of Northwell Health, the largest health care provider and private employer in New York. Home to 50 research labs, 2,500 clinical research studies and 4,000 researchers and staff, the Feinstein Institutes is raising the standard of medical innovation through its five institutes of behavioral science, bioelectronic medicine, cancer, health innovations and outcomes, and molecular medicine. We're making breakthroughs in genetics, oncology, brain research, mental health, autoimmunity, and bioelectronic medicine a new field of science that has the potential to revolutionize medicine. For more information about how we're producing knowledge to cure disease, visit feinstein.northwell.edu.

SOURCE The Feinstein Institutes for Medical Research

http://www.feinstein.northwell.edu

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New research casts doubt on near reality of 'designer babies' - PRNewswire

Autoimmune diseases are immune system disorders where the bodys immune system attacks its own tissues. Examples of common autoimmune diseases include rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, type 1 diabetes, multiple sclerosis (MS) and others.

A peculiarity of autoimmune diseases is that they have many genes in common, but they develop differently. For example, why does a patient with an autoimmune disease become a type 1 diabetic rather than have rheumatoid arthritis?

Decio L. Eizirik, a researcher at Universit Libre de Bruxelles Centre for Diabetes Research in Belgium, who is also a senior research fellow at the Indiana Biosciences Research Institute, recently published research in the journal Nature Genetics that found significant insight into this question. Eizirik took time to speak with BioSpace about the research and how a researcher in Belgium came to collaborate with researchers in Indiana, Spain, the UK and the U.S. National Institutes of Health.

Several autoimmune diseases, such as type 1 diabetes, rheumatoid arthritis, multiple sclerosis, etc., have as much as 30 to 50% of their candidates genes in common, said Eizirik, raising the question on why in some individuals the immune system attacks, for instance, the insulin-producing beta cells, causing type 1 diabetes, while in others it targets joint tissues, leading to rheumatoid arthritis. Most of the research in the field has focused on the role for these candidate genes on the immune system, but our work indicated that many of these candidates genes affect the function and survival of pancreatic beta cells, leading to a misguided dialogue between them and the immune system that culminates in diabetes.

The early stages of type 1 diabetes, for example, show local autoimmune inflammation and progressive loss of the pancreatic beta cells that produce insulin. How these genetic transcription factors, or cytokines, interact with the beta-cell regulatory environment, and the changes that occur, suggest a key role in how the immune system gets triggered to attack the beta cells.

The research was conducted by Eizirik, Lorenzo Pasquali from the Institucio Catalana de Recerca I Estudis Avancats (ICREA) in Barcelona, Spain, and colleagues from Oxford, UK; Pisa, Italy, and the NIH. For about 20 years, Eizirik has run a diabetes-focused laboratory in Brussels. In August 2019, he launched a new laboratory at the IBRI, where, he said, three top scientists and assistants, Donalyn Scheuner, senior staff scientist at IBRI, Bill Carter, research analyst at IBRI, and Annie Rocio Pineros Alvarez, postdoctoral fellow in medicine at Indiana University, are already working. These two laboratories are working closely togetherfor instance, we have weekly meetings by videoconference, and besides my regular visits to the IBRI, scientists are moving between our European and USA labs on a temporary or permanent basis.

The IBIR was created by the State of Indiana and the states leading life science companies, academic research universities and medical school, as well as philanthropic organizations. The focus is on metabolic disease, including diabetes, cardiovascular disease obesity and poor nutrition. Its laboratories and offices are housed in about 20,000 square feet of space in Indian University School of Medicines Biotechnology Research and Training Center in Indianapolis. It expects to move into a new 68,000-square-feet site in mid-2020.

Eizirik said, The IBRI offers a unique opportunity to translate our basic research findings to the clinic, and we are working closely together with colleagues at Indiana University, particularly Carmella Evans-Molina, director of the Indiana Diabetes Research Center (IDRC) and the IDRC Islet and Physiology Core, to confirm our basic research findings in patients samples, and to eventually bring them to the clinic.

The specific research study looked at the binding of tissue-specific transcription factors. Transcription factors are basically proteins whose job it is to turn genes on or off by binding to DNA. So, for example, there are specific transcription factors whose job it is to regulate insulin production in pancreatic beta cells. In the case of this research, Eizirik and his team studied tissue-specific transcription factors that open the chromatin. Chromatin is a complex of DNA and protein found in the nucleus of the cell. It allows long DNA molecules to be packaged, typically in the form of chromosomes.

For gene transcription to occur, Eizirik said, chromatin must open and provide access to transcription factors. This allows binding of pro-inflammatory transcription factors induced in the beta cells by local inflammation.

For certain people who are genetically predisposed to type 1 diabetes, this leads to the generation of signals by the beta cells, Eizirik said, that contribute to attract and activate immune cells, rendering beta cells a potential target to the immune system.

Eizirik said, These observations have clarified the role for pancreatic beta cells in type 1 diabetes and provided an explanation for the reasons behind the immune system targeting beta cells.

The amplifying loop mechanism observed potentially explains other autoimmune diseases. Eizirik notes, Binding of tissue-specific transcription factors, within an inflammatory context and in genetically predisposed individuals, could generate signals that would attract and activate immune cells against specific target tissues.

Testing the theory in other autoimmune diseases will be required to verify it, but potentially could open up new therapies or preventive treatments for type 1 diabetes and other autoimmune diseases.

Type 1 diabetes has a strong genetic component, Eizirik said. At least 50% of the disease risk is due to genetic causesand understanding the role for candidate genes in the disease may point to novel therapies. For instance, up to now, nearly all therapeutic approaches to prevent type 1 diabetes have targeted the immune system, with little success. Our findings suggest that we must also take steps to directly boost beta cell survival.

He compared targeting the immune system only in type 1 diabetes to trying to fly a plane with only one wing. Our present and previous data suggest that we need two wings: first, to re-educate the immune system to stop its attack on the beta cells, and second, to increase the beta cell resistance to the immune attack, and to find means to restore the lost beta cell mass. Unfortunately, to achieve these goals in both type 1 diabetes and other autoimmune diseases is not easy, and we must redouble our efforts.

The next stages of the research will be to study the function of two novel candidate genes for type 1 diabetes that were discovered in the research. They both act at the beta cell level. He expects to conduct that research with Pasquali. The second stage is to evaluate the impact of other immune mediators that act earlier in the disease course at the beta cell level. And the third stage is to test their hypothesis regarding the role for the target tissue in other autoimmune diseases.

In addition to that ambitious agenda, Eizirik and his group are establishing an Inducible Pluripotential Cell Core at the IBRI.

Eizirik said, This will allow us to de-differentiate, for instance, skin cells from patients into pluripotential cells, and then to differentiate them into pancreatic beta cells. This will allow us to study the impact of the novel candidate genes we are discovering on beta cell function and survival, again in collaboration with Lorenzo Pasquali and Carmella Evans-Molina. This will also provide an excellent model to test new drugs to protect the beta cells in early type 1 diabetes.

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Researchers Working to Understand Why Some Patients with Autoimmune Diseases Develop Diabetes Instead of Arthritis - BioSpace

DUBLIN--(BUSINESS WIRE)--The "Global Cancer Biomarkers Market Analysis 2019" report has been added to ResearchAndMarkets.com's offering.

The Global Cancer Biomarkers market is expected to reach $37.99 billion by 2026 growing at a CAGR of 14.2% from 2018 to 2026.

Factors such as rise in technological advancements and increase in Incidence of Cancer diseases are driving the market growth. Though, high capital investment and technical issues related to sample collection and storage are projected to inhibit the growth of the market. Moreover, emerging economies and personalized medicine may provide ample opportunities for the market growth.

By biomarker type, protein biomarkers segment acquired significant growth in the market is mainly attributed to the tremendous capability of protein biomarkers in cancer detection, diagnostics, prognostics, and clinical & therapeutic applications; and minimal cost of the protein biomarker tests as contrasted with genetic biomarker tests. The rising focus of pharmaceutical organizations towards the discovery of protein biomarkers is additionally expected to fuel the development of this market during the forecast period.

The key vendors mentioned are Qiagen N.V., Thermo Fisher Scientific, GE Healthcare, Roche Diagnostics, Abbott Laboratories, Illumina, Danaher Corporation, Agilent Technologies, Sysmex Corporation, Merck & Co., Quest Diagnostics, Becton, Dickinson and Company, Hologic, Myriad Genetics, Bio-Rad Laboratories and Biomrieux S.A.

Key Questions Answered in this Report

Key Topics Covered

1 Market Synopsis

2 Research Outline

2.1 Research Snapshot

2.2 Research Methodology

2.3 Research Sources

2.3.1 Primary Research Sources

2.3.2 Secondary Research Sources

3 Market Dynamics

3.1 Drivers

3.2 Restraints

4 Market Environment

4.1 Bargaining power of suppliers

4.2 Bargaining power of buyers

4.3 Threat of substitutes

4.4 Threat of new entrants

4.5 Competitive rivalry

5 Global Cancer Biomarkers Market, By Category

5.1 Introduction

5.2 Cancer Biomakers of Disease

5.3 Cancer Biomakers of Exposure

6 Global Cancer Biomarkers Market, By Method

6.1 Introduction

6.2 Assay Development

6.3 Biomarkers and Testing

6.4 Sample Preparation

7 Global Cancer Biomarkers Market, By Biomarker Type

7.1 Introduction

7.2 Cancer Antigen 15-3 (CA 15-3)

7.3 Cancer Antigen 27-29 (CA27-29)

7.4 Carbohydrate Antigen 19-9 (CA 19-9)

7.5 Carcinoembryonic antigen (CEA)

7.6 Epigenetic Biomarkers

7.7 Genetic Biomarkers

7.8 Glass Transition Temperature (Tg)

7.9 Glyco-biomarkers

7.10 Glycomic Biomakers

7.11 Glycoprotein Biomarkers

7.12 Human Chorionic Gonadotropin (Hcg)

7.13 Human Epidermal Growth Factor Receptor 2 (HER2)

7.14 Human Epididymis Protein 4 (HE4)

7.15 Metabolic Biomakers

7.16 Microsatellite Instability (MSI) / Measles, Mumps and Rubella (MMR)

7.17 Protein Biomarkers

7.18 Proteomic Biomarkers

7.19 Risk of Ovarian Malignancy Algorithm (ROMA)

7.20 Tumor Mutational Burden (TMB)

7.21 Tumor-Infiltrating Lymphocytes (TILs)

8 Global Cancer Biomarkers Market, By Cancer Type

8.1 Introduction

8.2 Bladder Cancer

8.3 Blood Cancer

8.4 Breast Cancer

8.5 Cervical Cancer

8.6 Colorectal Cancer (CRC)

8.7 Kidney Cancer

8.8 Leukemia

8.9 Liver Cancer

8.10 Lung Cancer

8.11 Melanoma

8.12 Non-Hodgkin's Lymphoma

8.13 Ovarian Cancer

8.14 Prostate Cancer

8.15 Stomach Cancer

8.16 Thyroid Cancer

9 Global Cancer Biomarkers Market, By Technology

9.1 Introduction

9.2 Bioinformatics

9.3 Cytogenetics-based Tests

9.4 Imaging Technologies

9.5 Immunoassays

9.6 IVD Multivariate Index Assays

9.7 Omic technologies

10 Global Cancer Biomarkers Market, By Test Type

10.1 Introduction

10.2 Alpha-Fetoprotein (AFP) Tests

10.3 Anaplastic Lymphoma Receptor Tyrosine Kinase Gene (ALK) Tests

10.4 BReast CAncer gene (BRCA) Tests

10.5 Cancer Antigen (CA) Tests

10.6 Carcinoembryonic Antigen (CEA) Tests

10.7 Circulating Tumor Cell (CTC) Tests

10.8 Companion Diagnostic Tests (CDx)

10.9 Estimated Glomerular Filtration Rate (EGFR) Mutation Tests

10.10 Human Epidermal Growth Factor Receptor 2 (HER2) Tests

10.11 Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) Mutation Tests

10.12 Laboratory Developed Tests (LDTs)

10.13 Prostate-specific Antigen (PSA) Tests

11 Global Cancer Biomarkers Market, By Analytical Technique

11.1 Introduction

11.2 Immunohistochemistry (IHC)

11.3 Next Generation Sequencing (NGS)

11.4 Polymerase Chain Reaction (PCR)

12 Global Cancer Biomarkers Market, By Product

12.1 Introduction

Excerpt from:
Global Cancer Biomarkers Market, Forecast to 2026 - Emerging Economies & Personalized Medicine to Provide Ample Industry Opportunities -...

Mila Makovec has high pigtails in her dark hair and a cloth doll tucked under her arm as she wakes up in a hospital bed, where shes just been injected with a one-of-a-kind drug intended to save her life.

The drug works for only one person in the world this 9-year-old girl from Boulder.

In a spectacular example of what the future might hold for precision medicine, the drug was made only for her in a quest to save Mila from a neurological disease that is destroying her brain. Her DNA is in the formula. The 22-letter genome sequence in the drugs recipe matches the one in Milas cells that is broken.

It is the first time the FDA has approved a drug for a single person.

The drug appropriately called milasen might not have come soon enough to save Mila, as it can only slow the process of degeneration, not replace the brain cells that have already died.

But this story is no longer just about Mila; it never actually was.

This is not just for my daughter anymore, said Julia Vitarello, who took to social media to fundraise and find a researcher and drug manufacturer who would help her. This is for something much bigger.

Milas case catapulted specialized drug development at least a decade into the future, her doctors say, opening a new path for other children with rare genetic diseases that have no cure.

Childrens Hospital Colorado, where Mila was diagnosed three years ago and now receives her treatment, and Boston Childrens, where her drug was designed, are leading the way in creating a model in which academic researchers could help perhaps a handful of children each year by crafting one-of-a-kind medicines. Next year, Childrens Colorado will begin whole-genome sequencing with a new machine called a Novaseq, a major step in the process of finding mutations in DNA.

The whole concept raises ethical questions for sure: How safe is it to initiate a clinical trial for a single child? Who makes sure the children who could benefit most not just those whose families have money or the ability to raise money get the specialized treatment?

Vitarello, who created Milas Miracle Foundation and raised $3 million while trying to save her daughter, wants to establish funding for children who need drugs tailored to their own cellular biology. She suggests an admissions process where the researchers deciding whether to help a child do not know that childs name, face or ability to pay.

There are going to be parents who are going to do anything for their kid, Vitarello said. They are going to come with money. Thats totally fine, no judgment. I would do the same thing. But in an ideal world, there would be patients coming through a funnel with no names or faces or money attached. Whoever is at the table makes the best decision.

The path forward is likely in the academic, nonprofit space, Vitraello said. She is initiating talks with the National Institutes of Health, the largest public funder of biomedical research, as well as research institutions, the FDA and the pharmaceutical industry. An estimated 1.3 million people with rare genetic diseases could potentially benefit from a treatment like Milas, she said.

There are 1.3 million kids that are dying that have no other treatment, no pharma company is going to help them, there is nothing that we can do, and now suddenly, weve opened up a pathway for that, she said Tuesday at the hospital in Aurora, as Mila rested following her injection. The only way to get it is to have more academic institutions treat more kids one, two, five, 10. Open it up.

The goal is that kids with flaws in their DNA could receive precision medicine sooner, halting neurological diseases before they steal the ability to walk, talk, eat or see.

Mila was a perfectly healthy child the first three years of her life. She was learning to ski, went hiking with her parents and had a vocabulary advanced beyond her years.

Her mom noticed the subtle changes before anyone the way she pulled books close to her face because she couldnt see, how her feet turned inward, that she began bumping into things and fell for no reason, how she stuttered sometimes but it wasnt like typical stuttering.

Vitarello brought her to 100 doctors and therapists from the East Coast to the West and in Canada, many of whom told her to calm down and that her daughter seemed fine. I had doctors tell me I was pretty much crazy. Very top level doctors told me to chill out, she said. Well, I wasnt going to chill out. I just kept going.

By age 7, Mila was having trouble walking and eating and was going blind. Her body was wracked with multiple seizures each day.

I spent three years trying to figure out what was wrong with her, Vitarello said. I basically gave up and brought her to the ER at Childrens Colorado.

Mila was admitted and her case assigned to Dr. Austin Larson, a geneticist whose main job at the hospital is to figure out whats wrong with patients who have an undiagnosed disease. An MRI found that the part of Milas brain that is responsible for balance, the cerebellum, was smaller than expected. But it was a genetic test that for the first time gave Vitarello a name for Milas illness: Batten disease, and a specific type of Batten that is so rare, just 25 people in the world are known to have it.

The disease occurs when both of a childs two CNL7 genes are mutated one mutation from each parent.

Larson was able to identify the defective gene from Milas father, but could not find one from her mother. At the time, Childrens Colorado along with most places didnt have the technology to search that deeply into Milas DNA through whole-genome sequencing, and Larson warned Milas family that it was likely impossible to find a clinical lab that could. She would need a researcher.

Vitarello turned to Facebook, begging for help for Mila but also so she could find out if her son, who was 2 at the time and completely healthy, had the same devastating disease that was taking away her daughter.

I was going to get nowhere with Mila unless I just opened up my story fully, to everyone, her mom said.

Dr. Larson had given her enough information and the right words to make a plea. A Boston physician saw her message and connected her with Dr. Timothy Yu, a neurogeneticist at Boston Childrens.

At the same time, the FDA had just approved a new drug called Spinraza, the first drug to treat a separate genetic condition called spinal muscular atrophy. The drug, injected into the fluid around the spinal cord, helped babies in clinical trials improve head control, sitting and standing.

The way Spinraza was designed was a game-changer for medicine and key in helping Mila. Yu and his team in Boston wondered if they could make a similar drug for the Colorado girl.

The Boston team spent days staring at screens of Milas DNA sequences until they discovered the other piece of the genetic puzzle in addition to the gene mutation from her father, Mila had inherited extra genetic material from her mother. The combination meant that, in the most basic terms, Mila had a sequence of broken DNA in her cells.

The drug created only for Mila contains little pieces of synthetic genetic material that search for a specific 22-letter sequence and cover it up so that her cells cannot read it. We are taking a Band-Aid and sticking it onto that part, said Dr. Scott Demarest, a pediatric neurologist at Childrens Colorado and a specialist in rare genetic epilepsies. That is literally what is happening. It is sticking to that spot so that the cell skips over that and goes to the next part that is correct.

The only difference between Spinraza and milasen is the genetic sequence inside the drugs send Band-Aids to different addresses.

After discovering the genetic flaw, Yu in Boston and Larson in Colorado called Milas mom together to give her the news. Her son did not have either of the recessive genes, and her daughter had both.

It was a huge mix of extreme happiness and, within the same second, just extreme falling-to-the-floor sadness for Mila, Vitarello recalled. My daughter had gotten both of the bad mutations and my son had gotten both of the good ones.

Next, Vitarello had to persuade a drugmaker to make a drug for one, and the FDA to allow doctors to inject it in her daughters spinal fluid.

The stars aligned, she says, still in disbelief.

Milas team made it happen by emphasizing that although this drug had the potential to work only on one person, the process could become a blueprint for other patients. Only the DNA sequence in the medicine would change.

They persuaded a drug manufacturer in California, TriLink Biotechnologies, to make Milas drug. And the FDA agreed to speed up the clinical trial process by allowing Yu to test the drug on rats at the same time Mila was receiving her first dose. The doctor had first tested it on Milas skin cells.

Milasen is technically now in clinical trial a trial of one patient involving two childrens hospitals.

The night before Milas first injection in January 2018, as Vitarello went for a run in subzero Boston, she told herself she was OK with whatever happened. Mila was out of time. Vitarello had seen the descriptions online and knew where Mila was headed.

My daughters trajectory of not treating her was so black and white, Vitarello said. Everyone always wonders what is going to happen to your life. When you have a rare disease, you can see exactly what is going to happen to your child ahead of time and its not a good thing.

I figured the worst-case scenario was not her dying, it was her being in pain, Vitarello said, recalling that she asked Yu to tell the FDA that she thought the drugs potential benefits outweighed the risk. I said, If my daughter dies on the spot, Im OK with that.

Instead, the injections that first year seemed to stop the diseases progression. Mila quit eating through a g-tube and started eating her moms pureed food again. She could hold up her head and her upper body, and her walking improved. Her seizures decreased from 30 a day to two or three.

Quality of life, those are huge, Vitarello said.

Now in the second year of treatment, some of Milas symptoms have declined, but not as steeply as other children with her disease. Milas team has upped her doses and started injecting them every two months instead of every three, but they have no precedent to follow.

They could find out years from now that they were giving Mila 1,000 times too little, her mother said.

I honestly dont know if it was in time for Mila, Vitarello said. She was really progressed when she received her treatment. There is still hope.

The key to saving more children from rare genetic diseases is diagnosing them earlier ideally at birth.

What if we found this three years sooner? Larson asked. I think about that a lot. What would it have taken to have found this the first time that (Vitarello) took Mila to a physician and said, I am concerned about the subtle difference in the way she walks?

The answer is it takes having a very broad test and being very good at interpreting that very broad swath of information.

Science is a ways off from being able to detect diseases as rare as Milas in newborns. But breakthroughs are coming for other genetic diseases.

Starting in January, spinal muscular atrophy will become one of 38 genetic diseases newborn babies are screened for via blood tests, said Raphe Schwartz, chief strategy officer for Childrens.

Childrens intends to take what it has learned through Milas case, partner with other institutions and use it to help more children, Schwartz said. What we learn reveals the roadmap for the future, he said. The future ones we do are more effective and less expensive over time.

There is a sense of urgency, but also caution.

We want to make sure we are doing it right, we are doing it safely, we are doing it for kids who are going to benefit the most, Demarest said. There are ethical challenges around it. We need to be very thoughtful and careful that we are doing this the right way, but were also doing it in a way that allows this to be a reality for kids as soon as possible and for as many as possible.

For now, Vitarello is grateful that Mila can receive her treatments in Colorado. Until September, they were traveling to Boston every other month for 10 days, but now they can leave home after breakfast on treatment days and return by dinner.

On Tuesday, Vitarello recited Goldilocks and the Three Bears and sang camp songs while Mila, bundled in blankets, received the 10-minute injection in her lower back, which Vitarello said doesnt seem to hurt Mila. They celebrated Milas 9th birthday last week, and her little brother, now 5, picked out a squishy toy and a sequined mermaid for her birthday presents.

Im faced with a huge amount of sadness around this, but at the same time, its making such a huge difference that it gives a lot of purpose to her life and it gives a lot of purpose to my life, Vitarello said. We are still fighting hard for Mila. But I can see this making a much bigger impact.

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This miracle drug was designed and manufactured for just one person a 9-year-old Boulder girl - The Colorado Sun

The Food and Drug Administration has halted a clinical trial of Novartis Zolgensma gene therapy due to a safety concern found in an animal study, the company said Wednesday.

The hold affects the Novartis (NVS) clinical trial known as STRONG, which was testing a higher dose of Zolgensma administered by spinal injection to older children with spinal muscular atrophy (SMA). It does not affect the already approved treatment of infants and children.

Novartis said its subsidiary AveXis informed regulators about findings from an animal study that showed dorsal root ganglia (DRG) mononuclear cell inflammation, sometimes accompanied by neuronal cell body degeneration or loss. The clinical significance of this adverse safety signal is not known, but it can be associated with sensory effects, the company added.

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Halting the STRONG clinical trial is a setback for Novartis effort to expand the use of Zolgensma to older patients with SMA. Biogens Spinraza treatment is already approved for older SMA patients. Roche (RHHBY) is expected to secure approval of its own SMA treatment next year.

Novartis said it has seen no reports of sensory effects in patients and is working with the FDA to resolve safety concerns and resume dosing of Zolgensma in the clinical trial.

The FDAs action on Wednesday follows a controversy involving manipulation of data used to support Zolgensmas approval. In an unusual rebuke, the agency said in August that AveXis knew that preclinical data had been falsified before the drug was approved in May, but did not inform the agency until later. The agency said that the drug should stay on the market, but the scandal sparked anger from lawmakers and a pledge from Novartiss CEO, Vas Narasimhan, to move more quickly on disclosing issues around data integrity.

Zolgensma carries a price tag of $2.1 million, making it the worlds most expensive medicine. Earlier this month, Novartis said the gene therapy had been used to treat 100 patients since its launch and brought in $160 million in the third quarter, beating analysts expectations.

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Novartis' Zolgensma gene therapy study halted on animal safety concerns - STAT

KENDALLVILLE Eighteen-month-old Omarion Jordan plays with his toys in his Kendallville home under the watchful eye of his mother, Kristin Simpson, and the family dog. He's wiggly and active, with no hint of the rare genetic disease that could have taken his life before age2.

Omarion has a rare genetic disorder called severe combined immunodeficiency syndrome, SCID for short and better known as the bubble boy disease made famous in a 1976 television movie starring John Travolta as well as an episode of the 1990s sitcom Seinfeld. The disease affecting 40 to 100 American newborns each year makes them extremely vulnerable to infections, which left untreated, kills most children before they turn two. Simpson said SCID is caused by a random gene mutation on the maternal side. She said she has no family history that would indicate it was present in family members.

Omarion was born normally, but began to have skin infection symptoms before he was 3-months-old, she said. Doctors thought he had an extreme case of eczema or cradle cap.

Simpson said everything changed when Omarion got his 3-month vaccinations.

He had a bad reaction. He had no immune system to react with the vaccine, she said. He was covered in a green, pus-like substance.

Simpson took Omarion to the emergency room twice, but was sent home. She then made an appointment with her pediatrician, not knowing then that it would be months before she saw her apartment again.

The pediatrician sent us right to the hospital, Simpson said. It was 11/2 weeks to clear the infection. I had to drop everything. I never came back (to the apartment) after that morning.

Doctors sent Omarion and his mother on a four-hour ambulance ride to Cincinnati Children's Hospital for tests. There, Simpson learned that the standard treatment for SCID was a bone marrow transplant. When a two-month search for a bone marrow match came up empty, doctors suggested another route.

There was a trial at St. Jude (Children's Hospital) for gene therapy and we were given the option, Simpson said. We were flown to St. Jude's on a private jet.

The experimental gene therapy used Omarion's own bone marrow, altered to correct the missing gene. The altered bone marrow is transplanted back into Omarion's body, carried by an HIV virus with all the harmful cells removed.

It's like a car, Simpson said. They take out the harmful elements and use the virus as a carrier for the altered gene.

Experimental gene therapy comes with both reward and risk. The treatment could be a breakthrough cure for Omarion and other children affected by the gene mutation.

The risks include developing leukemia, which has happened to some patients in the small trial group, other unknown side effects and the enormous financial cost. Treatment costs run into the millions of dollars.

Gene therapies, while breaking new ground in fighting tough-to-cure ailments, are a cutting edge field of medicine, but also an exceptionally expensive one. For example, a gene therapy drug called Zolgensma is the most expensive drug ever approved in the United States, according to a Bloomberg Businessweek story about Omarion and the rise of gene therapies. A one-time infusion costs $2.1 million.

Omarion's case has received national media attention, including the story from Bloomberg Businessweek, which published a story June 5 about the balance of rapidly progressing gene therapy and its high cost, and other outlets including NBC News, WebMD.com and CNN Health.

Simpson is grateful that St. Jude's Children Hospital, the world's leader in the treatment of childhood diseases, has picked up the entire tab for Omarion's treatment.

Simpson said that at St. Jude, she and her mother were the only family members allowed inside Omarion's isolation room. Everyone else was fully masked and gowned. They were in the isolation room for months.

Omarion received his bone marrow transplant Dec. 20, 2018, and finally left the hospital in April. Omarion will have checkups every three months for the foreseeable future and an annual checkup for the rest of his life.

Today he's healthy, thanks to a cutting-edge gene therapy treatment, and a walking miracle.

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Gene therapy gives toddler second chance | Indiana | Journal Gazette - Fort Wayne Journal Gazette

Fighting Blindness Canadas secure, clinical patient registry is a database dedicated to connecting people living with retinal eye diseases to clinical trials and research.Paffy69 / PNG

Blind and partially sighted people no longer have to wait passively for a research breakthrough in hope of treatment options. In fact, people living with genetic eye conditions can now actively drive vision research forward by enrolling in a patient registry and getting their genes tested.

There are 2.2 billion people living with visual impairment globally. Some are living with inherited retinal diseases that are progressive and can lead to complete blindness. Up until recent years, blind and visually impaired people were told that no treatment is available. This is changing as genetic testing is paving the way for a surge of gene therapies.

My doctoral dissertation at the University of B.C. was on drug therapy for retinitis pigmentosa. This progressive, blinding eye condition is the most common type of inherited retinal disease.

In people affected by retinitis pigmentosa, the light sensing cells in their retina photoreceptors die early. Unlike skin cells that regenerate, the body does not make more photoreceptors once they are damaged.

As a vision scientist affected by retinitis pigmentosa, I am passionate about finding the truth about the disease. Why do photoreceptors die? How can we stop it? How can science and medicine help?

When I was 12 years old, I realized while at summer camp that my night vision was disappearing. In the last two decades, I lost my peripheral vision, contrast sensitivity and depth perception.

I worked in Dr. Orson Moritzs lab at the UBC department of ophthalmology and visual sciences, which focuses on research using tadpoles that contain known human mutations for retinitis pigmentosa to understand the disease.

I made an alarming discovery in our animal model: knowing the genetic cause of retinitis pigmentosa is vital for treatment with one class of drugs histone deacetylase inhibitors. These determine how genes are switched on or off.

A similar study in mice showed that the same drug reacted differently to variations in a single mutant gene that also causes retinitis pigmentosa.

Treating retinitis pigmentosa is like extinguishing fire. To stop a fire, you need to know whether its water-based or grease-based. If you try to use water to stop a grease fire, the damage gets worse.

Blind and visually impaired people can advocate for eye health by enrolling in a patient registry. Participation in a registry benefits researchers by offering more information about the disease.

In Canada, individuals can self-refer to Fighting Blindness Canadas secure, clinical patient registry. This database is dedicated to connecting people living with retinal eye diseases to clinical trials and research.

When a gene therapy trial arises, researchers draw participants from this database. Since gene therapy aims to correct an underlying genetic mistake in DNA that causes disease, knowing the genetic cause of a disease is a criteria for most gene therapy trials.

Globally, other registries include My Retina Tracker in the United States, Target 5000 in Ireland, MyEyeSite in the United Kingdom, the Australian Inherited Retinal Disease Registry and Japan Eye Genetics Consortium. In New Zealand, Dr. Andrea Vincent has established the Genetic Eye Disease Investigation Unit. There is even a Blue Cone Monochromacy Patient Registry for one rare eye condition.

In the last two decades, the number of gene therapy trials has blossomed. Currently, 250 genes on inherited retinal diseases have been identified. In 2017, the first gene therapy for inherited retinal disease Luxturna was approved by the United States Federal Drug Administration.

To date, there are trials for: retinitis pigmentosa; Usher syndrome, a condition that involves hearing and vision loss; achromatopsia, a disease that causes colour blindness; X-linked retinoschisis, a dystrophy that causes splitting of the retina and affects mostly in males; and age-related macular degeneration, the third-largest cause of vision loss worldwide, caused by the interplay between genetics and environment.

Enrolment in a patient registry and genetic testing advance the design of gene therapy trials. This in turn benefits blind and visually impaired people.

Research advancement is a concerted effort across the globe blind and partially sighted people should know they have the power to push it forward.

Ruanne Vent-Schmidt is a PhD candidate in cell and developmental biology at the University of B.C.This article originally appeared online at theconversation.com, an independent source of news and views, from the academic and research community.

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Ruanne Vent-Schmidt: The blind and visually impaired can help researchers by getting their genes tested - Vancouver Sun