Category Archives: New York Stem Cells

Scientists and doctors have made tremendous advances in moving regenerative medicine into the mainstream as a treatment for many diseases and disorders. Regenerative medicine takes advantage of our natural ability to heal ourselves by using the healthy adult stem cells found throughout the body. Laboratory and clinical research has shown that it is possible to use adult stem cells to restore lost, damaged or aging cells to effectively regenerate tissue and provide some patients with an alternative to surgery. Regenerative therapies are showing promise in orthopedic medicine, wound care, nerve restoration, and a variety of cardiovascular, neuromuscular, and autoimmune conditions.

Adult stem cells were discovered over 40 years ago when researchers found that cells derived from bone marrow had the ability to form various tissues. Adult stem cells are early stage cells that, under the right conditions, are capable of developing into other types of cells and hold the potential to regenerate damaged tissue.

AUTOLOGOUS ADULT STEM CELLS (ASCS) are being used to treat many types of chronic pain and degeneration. Currently doctors are treating shoulder, knee, hip, and spine degeneration, in addition to soft tissue (muscle, tendon, ligament) and other bone related injuries.

The first step is to determine if you are a good candidate for an adult stem cell procedure. Your physician will want a history of your injury and a physical examination along with any x-rays, and an MRI. While stem cell therapy maybe appropriate for certain conditions, it is not applicable for every condition. However, it is has proven to be a viable option for several individuals suffering from pain. Good candidates for adult stem cell treatment usually are:

Every patient is different, the success of the stem cell therapy is dependent on the severity of your condition and your bodys response to stem cell therapy.

Overview of the Procedure

An adult stem cell procedure harnesses and amplifies the bodys natural mechanism for healing and anti-inflammation. Once you have been identified as a good candidate for the procedure, a member of our team will review the procedure with you and answer any questions that you may have. A brief overview of the procedure is below:

Once the procedure is complete, our staff will allow you to rest and will create a customized personal rehabilitation program for recovery. We will either ask you to come back for a few post-operative appointments or follow up with you by phone, email, or mail so we can track you healing progress.

Potential Applications

Frequently Asked Questions (FAQs)

Q: What are adult stem cells?

A: Adult stem cells are unspecialized or undifferentiated cells, capable of two processes: self-renewal and differentiation. They are vital to maintaining tissues in the body such as internal organs, skin, and blood.

Q: What is Regenerative Medicine?

A: Regenerative Medicine is a new and advancing scientific field focused on the repair and regeneration of damaged tissue utilizing stem cells.

Q: What is the difference between adult stem cells and embryonic stem cells?

A: Adult stem cells are found in mature adult tissues including bone marrow and fat, while embryonic stem cells (ESCs) are not found in the adult human body. ESCs are obtained from donated in vitro fertilizations, which raises many ethical concerns. Because ESCs are not autologous, there is a possibility of immune rejection. Adult stem cells do not raise ethical issues nor pose any risks for immune rejection.

Q: Does Dr. Youm use embryonic stem cells in clinical procedures?

A: No, Dr. Youms approach to cell therapy relies only on autologous adult stem cells isolated from the patient during surgery. He does not participate in embryonic stem cell research or use embryonic stem cells in clinical applications.

Q: Are there ethical issues associated with harvesting adult stem cells?

A: No, adult stem cells do not raise ethical questions as they are harvested from the patients body.

Q: Are there cancer-causing risks associated with adult stem cell treatments?

A: No. Where embryonic stem cells have been shown to form teratomas (germ cell tumors), there is no data that suggests adult stem cells have the same potential to promote the development of tumors.

Q: Where do adult stem cells come from?

A: In adults, stem cells are present within various tissues and organ systems, the most common being bone marrow and adipose or fat tissues. Other sources include the liver, epidermis, retina, skeletal muscle, intestine, brain, placenta, umbilical cord and dental pulp.

Q: How does Dr. Youm obtain adult stem cells for use in cell treatment?

A: Dr. Youm currently has a system that uses adult stem cells from bone marrow and these stem cells are obtained through aspiration during your procedure.

Q: How are adult stem cells used in surgical procedures?

A: Adult stem cells are used to treat patients with damaged tissues due to age or deterioration. During a procedure, stem cells are isolated from the patient, concentrated and delivered back to the site of injury to assist in the healing process.

Q: Are there different types of adult stem cells?

A: Yes, there are many types of adult stem cells found in the body, which have variable differentiation potentials. The adult stem cells that aid in the repair of damages tissue are multipotent, mesenchymal stem cells. These are located in bone marrow and adipose (fat) tissue.

Q: Are the harvested adult stem cells expanded in a laboratory setting prior to delivery back to the patient?

A: No, Dr. Youm does not use in vitro expansion. The cells are harvested, processed in the operating room and delivered back to the patient at point of care.

Q: How do stem cells know what type of tissue to develop into?

A: The differentiation of stem cells is dependent on many factors, including cell signaling and micro-environmental signals. Based on these cues, stem cells are able to develop into healthy tissue needed to repair damaged tissue. For example, multipotent stem cells delivered to damaged bone will develop into bone cells to aid in tissue repair. The exact mechanism of lineage-specific differentiation is unknown at this point.

Q: Will my body reject the stem cells?

A: No, adult stem cells are autologous and non-immunogenic.

Q: Is stem cell therapy safe?

A: Yes, and ask your doctor what clinical studies have been done to show that stem cells are safe and effective.

Q: Where are stem cells currently being used?

A: Stem cells are currently being used in both laboratory and clinical settings. Laboratories are using human and animal derived stem cells to conduct in vitro studies as well as in vivo studies with small and large animals. Autologous adult stem cells are currently being used in hospitals and clinics during surgery to aid in the repair of damaged tissues.

Q: How long will the stem cells last?

A: It will depend on your injury, the area that is treated and your response to the therapy.

Q: What is the recovery like after a stem cell procedure?

A: If you have a joint injection, you typically can go back to work. It is advised to limit load bearing activities for at least 2 weeks. If you had disc injections, you should take it easy for a few days. Non-steriodal, anti-inflammatory medications (NSAIDS) should be withheld for 72 hours pre-procedure and one week after the procedure.

Q: What is the difference between autologous and allogeneic cells?

A: Autologous cells are taken from the same patient, typically at point-of-care. Allogeneic cells are taken from another patient and are often manipulated before they are given to another patient.

Q: Why use adult stem cell therapy rather than pharmaceuticals or genetic treatments?

A: Adult stem cells are from the body and generate natural proteins and therapeutic biochemicals, decrease inflammation, are anti-bacterial, and recruit other cells to heal the injured site. Pharmaceutical treatments only provide drugs with minimally effective dosages that may cause unwanted side effects. Over dosage can be dangerously toxic or even carcinogenic. Genetic therapy is still unproven and serious concerns exist about it causing cancer due to genetically manipulated cells.

Q: What is the difference between autologous and allogeneic cells?

A: Autologous cells are taken from the same patient, typically at point-of-care. Allogeneic cells are taken from another patient and are often manipulated.

Q: How much will it cost?

A: Most insurance will not cover stem cell procedures. Ask your doctor for payment options

The use of Stem cells in Hip Therapies

The use of Stem cells in Knee Therapies

The use of Stem cells in Shoulder Therapies

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Stem Cell Therapy New York City | Regenerative Medicine ...

New York State Stem Cell Science Consortia

Center for Stem Cell Biology investigators are leading a multidisciplinary effort to develop a cell based therapy for the treatment of Parkinsons disease.

The Center for Stem Cell Biology (CSCB) was established in 2010 to serve as a hub for existing stem cell efforts at Memorial Sloan Kettering Cancer Center. The center also supports targeted recruitment of stem cell faculty and provides resources for stem cell research such as core facilities and trainings programs.

Memorial Sloan Kettering has been a leader in various aspects of stem cell research for many years. It has been at the forefront of realizing the potential of hematopoietic stem cells in the treatment of hematopoietic malignancies, the use of umbilical cord blood as a source of stem cells suitable for transplantation, and the isolation of human mesenchymal stem cells. In recent years research has expanded to new areas such as neural stem cells, embryonic stem cells, and induced pluripotent stem cells. The CSCB will link these existing stem cell research efforts and build the resources critical for new developments in the future.

To achieve these goals the CSCB will bring together scientists across various programs with a broad range of expertise in the following areas: cancer pathogenesis, cell biology, chemical biology, computational biology, developmental biology, and pharmacology. These partnerships will facilitate research projects that transcend traditional departmental boundaries to explore the full potential of stem cells, ranging from basic developmental studies to the use of human stem cells in drug discovery. Another core mission of the CSCB is the training of investigators in stem cell technologies such as induced pluripotency, directed differentiation, genetic modification, and prospective purification of stem cells. Finally, the CSCB links stem cell efforts at Memorial Sloan Kettering with the Tri-Institutional Stem Cell Initiative, a collaborative program of Memorial Sloan Kettering, The Rockefeller University, and Weill Cornell Medical College, as well as with other national and international stem cell organizations.

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Center for Stem Cell Biology | Memorial Sloan Kettering ...

When you sneeze, you leak urine. When you exercise, you leak urine. Man or woman, urinary incontinence is not something people discuss openly. Can we talk about it?

You wont read that many daily headlines about urologic disorders, certainly not when compared to issues like weight loss or heart disease, for example. Yet disorders of the urinary system are complicatedand common.

Are You Bothered by Bladder Pain or Leakage?

Its a fact. Millions of American women and men suffer from some form of urinary incontinence (UI). Women experience urine leakage more frequently, and there are a lot of reasons both genders lose bladder control now and then.

Urine leakage starts with the muscles and nerves that control the bladder. Located in the lower abdomen between the pelvic bones, the bladder is a muscular organ, roughly triangular in size, which expands and contracts to hold and release urine.

With a capacity to stretch from two to six inches in size, the bladder can hold between 16 and 24 ounces of fluid, about the size of a large soft drink. At a quarter full, messages are sent through the nervous system to signal you of the need to urinate and empty the bladder.

Within the bladder, a sphincter acts as a door to keep urine from leaking. When bladder muscles contract, they push out fluid as the sphincter relaxes to allow urine to pass. When bladder muscles contract prematurely, or the sphincter relaxes too oftenurine leakage can occur.

There Are Many Triggers of Urinary Incontinence

The bad news is that there many triggers for urinary leakage. The good news, is that many of these triggers are diet-related. This means if you avoid certain foods, you have a better chance of avoiding urine leakage.

Working to stimulate or irritate your bladder, steer clear of food and drinks with:

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New York Stem Cell Treatment Center

Dr. Norman Rowe is an expert plastic surgeon and is highly skilled in stem cell rejuvenation procedures. Stem cells are special cells in the body that can become any cell the body needs. The placement of these stem cells is what determines the kind of cell that they will become. For example, a stem cell placed in a bone becomes a bone cell and a stem cell placed in cartilage becomes cartilage. Dr. Rowe harvests stem cells from the fat under your skin through a light liposuction procedure and then, after processing, injects those stem cells into the skin of your face so the body can produce new, younger skin that is free of blemishes and age marks.

At your appointment, Dr. Rowe will first discuss the stem cell rejuvenation procedure with to be sure you are clear on the details. Through a bit of liposuction, Dr. Rowe will harvest stem cells from a fatty area of your body and then process them in his in-house lab, separating the fat cells from the stem cells. Dr. Rowe will then inject the stem cells into the areas of the face that you would like to look more youthful and rejuvenated. The whole procedure takes less than one hour to perform and there is very little downtime afterwards.

Stem cell rejuvenation is exceptionally effective for patients with deep lines and hollows in the face due to age. The stem cells will become the scaffolding of the skin and create a more youthful and full appearance to hollowed areas. There is also no risk of your body rejecting the injections, because they are your own stem cells. About one month after your stem cell rejuvenation procedure, youll see Dr. Rowe for a follow up appointment and by that time the injected stem cells should steadily be filling in the hollows and fine lines in your face. Results from stem cell rejuvenation can last for five years or more, which is much longer than dermal filler injections.

Dr. Rowe and his highly trained staff invite you to schedule a consultation appointment to learn more about Stem Cell Rejuvenation. A younger, more refreshed face is just a phone call away: 212-628-7300. You can also send us a message or request for a consultation or appointment using ouronline contact form.

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Stem Cell Rejuvenation New York - Norman Rowe MD

Parkinsons disease (PD) is the second most common neurodegenerative disorder and is estimated to affect more than four million patients worldwide a number predicted to more than double by 2030. A fundamental characteristic of PD is progressive, severe, and irreversible loss of specific dopamine-producing neurons (DA neurons) in the midbrain that ultimately may result in disabling motor dysfunction. Multiple therapies have been developed for PD, but none can replace the lost cells. Cell transplantation has been considered a promising therapy, but in spite of extensive efforts to develop it in laboratories across the world, this approach has faced multiple challenges, including the absence of an appropriate cell source that can match the lost cells in function and safety.

In 2011, our team made a major discovery that enables the derivation of nearly unlimited numbers of authentic, engraftable midbrain DA neurons from human embryonic stem cells (hESCs). In recent publications, we have demonstrated that these cells can survive in three independent PD models and can reverse motor deficits of the disease.

In addition, the cells have an excellent safety profile with no evidence of tumor or excessive growth in any of the animals tested.

The investigators anticipate that by the end of the project period in 2017, our team will be ready to submit an Investigational New Drug (IND) application to the US Food and Drug Administration for a clinical trial in Parkinsons patients. The team consists of scientists, neurologists, surgeons, industry leaders, ethicists, trial experts, and patient advocates who are dedicated to the achievement of this goal. The project further harnesses the expertise and strength present within Memorial Sloan Kettering at the Center for Cell Engineering (CCE) and the Center for Stem Cell Biology (CSCB) to deliver a first-in-man embryonic stem cell therapy for PD.

Investigators from Memorial Sloan Kettering, along with colleagues from Weill Cornell Medical College, Northwestern University, and Rush University Medical Center, have received a contract from New York State Stem Cell Science (NYSTEM) for almost $15 million over four years to develop a stem-cell-based therapy for Parkinsons disease. NYSTEM works to further the agenda of the Empire State Stem Cell Board, whose mission is to foster a strong stem cell research community in New York State.

NYSTEM aims to accelerate the growth of scientific knowledge about stem cell biology and promote the development of therapies and diagnostic methods to alleviate disease and improve human health. The NYSTEM contract has enabled the creation of a multidisciplinary consortium with the overarching goal of developing an optimized, clinical-grade source of human DA neurons for cell therapy in PD by 2017.

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New York State Stem Cell Science Consortia | Memorial ...

Inside the microscopic world of the mouse hair follicle, Yale Cancer Center researchers have discovered big clues about how stem cells regenerate and die. These findings, published April 6 in the journal Nature, could lead to a better understanding of how the stem cell pool is maintained or altered in tissues throughout the body.

Stem cells are undifferentiated cells that replenish themselves and, based on their tissue location, can become specialized cells such as blood or skin cells. The hair follicle is an ideal site for exploring stem cell behavior because it has distinct and predictable oscillations in the number and behavior of stem cells, said the studys lead author, Kailin R. Mesa, a third-year doctoral student in the lab of Valentina Greco, associate professor of genetics, cell biology, and dermatology.

Using live microscopic imaging to track stem cell behavior in the skin of living mice, researchers observed that the stem cell niche, or surrounding area, plays a critical role in whether stem cells grow or die.

Prior to this, it wasnt clear whether stem cell regulation was intrinsic or extrinsic, and now we know it is external in that the niche instructs the stem cells, Mesa said. In terms of cancer, we can next explore how we might perturb or change the niche in hopes of affecting the growth of cancer stem cells.

Also, researchers were surprised to find that the stem cells within the pool fed on other dying stem cells. This reveals a mechanism for removing dead cells, a process previously observed in mammary glands but never in the skin.

This study was supported by the Yale Dermatology Spore, National Institutes of Health, American Cancer Society, and New York Stem Cell Foundation.

Citation: Nature

(Photo via Shutterstock)

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Research in the News: Tiny hair follicle offers big clues about the life and death of stem cells

A particular molecular pathway permits stem cells in pediatric bone cancers to grow rapidly and aggressively, according to researchers at NYU Langone Medical Center and its Laura and Isaac Perlmutter Cancer Center.

In normal cell growth, the Hippo pathway, which controls organ size in animals, works as a dam, regulating cell proliferation. What the researchers found is that the transcription factor of a DNA binding protein called sex determining region Y box 2, or Sox2 for short, which normally maintains cell self-renewal, actually releases the floodgates in the Hippo pathway in osteosarcomas and other cancers, permitting the growth of highly aggressive, tumor-forming stem cells.

Results from the study are to be published in the journal Nature Communications online April 2.

"This study is one of the first to identify the mechanisms that underlie how an osteosarcoma cancer stem cell maintains its tumor-initiating properties," says senior study investigator Claudio Basilico, MD, the Jan T. Vilcek Professor of Molecular Pathogenesis at NYU Langone and a member of its Perlmutter Cancer Center.

In the study, the investigators used human and mouse osteosarcomas to pinpoint the molecular mechanisms that inhibit the tumor-suppressive Hippo pathway. The researchers concluded that Sox2 represses the functioning of the Hippo pathway, which, in turn, leads to an increase of the potent growth stimulator Yes Associated Protein, known as YAP, permitting cancer cell proliferation.

"Our research is an important step forward in developing novel targeted therapies for these highly aggressive cancers," says study co-investigator Alka Mansukhani, PhD, an associate professor at NYU Langone and also a member of the Perlmutter Cancer Center. "One possibility is to develop a small molecule that could knock out the Sox2 transcription factor and free the Hippo pathway to re-exert tumor suppression."

Mansukhani adds that the research suggests that drugs such as verteporfin, which interfere with cancer-promoting YAP function, might prove useful in Sox2-dependent tumors.

The study expands on previous work in Basilico's and Mansukhani's molecular oncology laboratories at NYU Langone and on earlier work by Upal Basu Roy, PhD, MPH, the lead study investigator, who found that Sox2 was an essential transcription factor for the maintenance of osteosarcoma stem cells.

The NYU group has shown that, i addition to playing a role in osteosarcoma, Sox2 operates in other tumors, such as glioblastomas, an aggressive type of brain cancer.

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Key mechanism identified in tumor-cell proliferation in pediatric bone cancers

NEW YORK, April 2, 2015 /PRNewswire-USNewswire/ --A particular molecular pathway permits stem cells in pediatric bone cancers to grow rapidly and aggressively, according to researchers at NYU Langone Medical Center and its Laura and Isaac Perlmutter Cancer Center.

In normal cell growth, the Hippo pathway, which controls organ size in animals, works as a dam, regulating cell proliferation. What the researchers found is that the transcription factor of a DNA binding protein called sex determining region Y box 2, or Sox2 for short, which normally maintains cell self-renewal, actually releases the floodgates in the Hippo pathway in osteosarcomas and other cancers, permitting the growth of highly aggressive, tumor-forming stem cells.

Results from the study are to be published in the journal Nature Communications online April 2.

"This study is one of the first to identify the mechanisms that underlie how an osteosarcoma cancer stem cell maintains its tumor-initiating properties," says senior study investigator Claudio Basilico, MD, the Jan T. Vilcek Professor of Molecular Pathogenesis at NYU Langone and a member of its Perlmutter Cancer Center.

In the study, the investigators used human and mouse osteosarcomas to pinpoint the molecular mechanisms that inhibit the tumor-suppressive Hippo pathway. The researchers concluded that Sox2 represses the functioning of the Hippo pathway, which, in turn, leads to an increase of the potent growth stimulator Yes Associated Protein, known as YAP, permitting cancer cell proliferation.

"Our research is an important step forward in developing novel targeted therapies for these highly aggressive cancers," says study co-investigator Alka Mansukhani, PhD, an associate professor at NYU Langone and also a member of the Perlmutter Cancer Center. "One possibility is to develop a small molecule that could knock out the Sox2 transcription factor and free the Hippo pathway to re-exert tumor suppression."

Mansukhani adds that the research suggests that drugs such as verteporfin, which interfere with cancer-promoting YAP function, might prove useful in Sox2-dependent tumors.

The study expands on previous work in Basilico's and Mansukhani's molecular oncology laboratories at NYU Langone and on earlier work by Upal Basu Roy, PhD, MPH, the lead study investigator, who found that Sox2 was an essential transcription factor for the maintenance of osteosarcoma stem cells.

The NYU group has shown that, i addition to playing a role in osteosarcoma, Sox2 operates in other tumors, such as glioblastomas, an aggressive type of brain cancer.

Besides Drs. Basilico, Mansukhani, and Basu Roy, study co-investigators, all from NYU Langone, include N. Sumru Bayin, PhD; Eugenia Han, MD; and Dimitris G. Placantonakis, MD, PhD.

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Key Mechanism Identified In Pediatric Bone Cancers That Allows Proliferation Of Tumor-Forming Stem Cells

(February 19, 2015) - The New York Stem Cell Foundation (NYSCF) and the Stanley Center at the Broad Institute of MIT and Harvard are partnering to create a foundational stem cell resource to study psychiatric disorders through the production of induced pluripotent stem (iPS) cell lines from individuals with schizophrenia and other psychiatric disorders.

This new partnership aligns NYSCF's mission to accelerate cures for the major disease of our time through stem cell research with the Stanley Center's goal to reduce the burden of serious mental illness through research. NYSCF is generating stem cell lines from skin samples of patients provided by the Stanley Center, which recently reported on the genotyping of more than 10,000 patients with schizophrenia. Research conducted using the stem cell lines generated will closely couple with ongoing genetic studies on the underpinning of psychiatric disease at the Stanley Center.

"This is a great example of how two non-profit organizations can work together to advance a cause which, in the short term, will help us better understand a misunderstood and difficult condition. In the longer term, it will help provide important information and approaches for drug discovery," said Dr. Steven Hyman, Director of the Stanley Center for Psychiatric Research at the Broad Institute of MIT and Harvard.

Once the stem cell lines have been generated, scientists at the Stanley Center will utilize the stem cell lines to study psychiatric disease. Using novel protocols, they will turn the iPS cells into the adult brain cell types that are affected in schizophrenia.

"We are thrilled to partner with the Stanley Center to develop this important resource for studying schizophrenia and other mental disorders. This collaboration combines the stem cell expertise and technological capabilities of NYSCF with the resources, patient access, and clinical knowledge of the Stanley Center," said Susan L. Solomon, NYSCF CEO and Founder.

iPS cells are remarkable because they can generate an endless supply of the diverse cells that compose our bodies. This characteristic makes these cells a promising tool for studying psychiatric disease and eventually devising therapies. Early efforts have suggested that many brain cell types can be made from iPS cells in such a way that they carry the genetic risk factors that predispose people to psychiatric disease. Living cells like these have never before been available for study, as the only source of such material was from autopsy samples. Thus, stem cell biology offers a promising avenue for understanding how the brain malfunctions in people with psychiatric disorders.

This collaboration will attempt to determine which of the many brain cell types that are changed in individuals with psychiatric disease and to understand how they are changed. These avenues of investigation, along with studies of the genetic underpinning of psychiatric disease, may provide great insight into the causes and potentially new treatments for psychiatric disease through the identification of drugs that correct the changes identified.

The genetic contributors to brain dysfunction are complex and it is known that both protective and predisposing genetic causes shape the likelihood of developing an illness like schizophrenia. As a result, utilizing this resource, scientists will have the opportunity to study the phenotypic effects of predisposing sequence variants on a genetic background that scientists can feel confident would not suppress the sequence variants.

NYSCF will generate the stem cell lines using The NYSCF Global Stem Cell ArrayTM, an automated, robotic technology capable of producing large numbers of identical stem cell lines. The Array technology allows for the creation of this large number standardized stem cell lines, effectively creating a panel representing the diverse cellular phenotypes and genotypes within schizophrenia - a task that has previously not been possible in the field. Scientists are beginning to better understand how to control stem cells in order to reproducibly generate large quantities of the many diverse cell types from the brain.

"This is an opportunity to unite the remarkable progress that has been made in genetic studies of psychiatric diseases with emerging technologies from NYSCF. This collaboration will help illuminate how carrying a genotype which predisposes one to schizophrenia fundamentally changes neuronal function and behavior," said Kevin Eggan, Director of the Stem Cell Program of the Stanley Center.

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Stanley Center at the Broad Institute and NYSCF partner to study psychiatric diseases

IMAGE:Induced pluripotent stem cell-derived motor neurons from an ALS patient (left) compared with normal cells (right). The cells are being used to study the role of the genes TBK1 and... view more

NEW YORK, NY (February 19, 2015)--Using advanced DNA sequencing methods, researchers have identified a new gene that is associated with sporadic amyotrophic lateral sclerosis (ALS), or Lou Gehrig's disease. ALS is a devastating neurodegenerative disorder that results in the loss of all voluntary movement and is fatal in the majority of cases. The next-generation genetic sequencing of the exomes (protein-coding portions) of 2,874 ALS patients and 6,405 controls represents the largest number of ALS patients to have been sequenced in a single study to date.

Though much is known about the genetic underpinnings of familial ALS, only a handful of genes have been definitively linked to sporadic ALS, which accounts for about 90 percent of all ALS cases. The newly associated gene, called TBK1, plays a key role at the intersection of two essential cellular pathways: inflammation (a reaction to injury or infection) and autophagy (a cellular process involved in the removal of damaged cellular components). The study, conducted by an international ALS consortium that includes scientists and clinicians from Columbia University Medical Center (CUMC), Biogen Idec, and HudsonAlpha Institute for Biotechnology, was published today in the online edition of Science.

"The identification of TBK1 is exciting for understanding ALS pathogenesis, especially since the inflammatory and autophagy pathways have been previously implicated in the disease," said Lucie Bruijn, PhD, Chief Scientist for The ALS Association. "The fact that TBK1 accounts for one percent of ALS adds significantly to our growing understanding of the genetic underpinnings of the disease. This study, which combines the efforts of over two dozen laboratories in six countries, also highlights the global and collaborative nature of ALS research today.

"This study shows us that large-scale genetic studies not only can work very well in ALS, but that they can help pinpoint key biological pathways relevant to ALS that then become the focus of targeted drug development efforts," said study co-leader David B. Goldstein, PhD, professor of genetics and development and director of the new Institute for Genomic Medicine at CUMC. "ALS is an incredibly diverse disease, caused by dozens of different genetic mutations, which we're only beginning to discover. The more of these mutations we identify, the better we can decipher--and influence--the pathways that lead to disease." The other co-leaders of the study are Richard M. Myers, PhD, president and scientific director of HudsonAlpha, and Tim Harris, PhD, DSc, Senior Vice President, Technology and Translational Sciences, Biogen Idec.

"These findings demonstrate the power of exome sequencing in the search for rare variants that predispose individuals to disease and in identifying potential points of intervention. We are following up by looking at the function of this pathway so that one day this research may benefit the patients living with ALS," said Dr. Harris. "The speed with which we were able to identify this pathway and begin our next phase of research shows the potential of novel, focused collaborations with the best academic scientists to advance our understanding of the molecular pathology of disease. This synergy is vital for both industry and the academic community, especially in the context of precision medicine and whole-genome sequencing."

"Industry and academia often do things together, but this is a perfect example of a large, complex project that required many parts, with equal contributions from Biogen Idec. Dr. Tim Harris, our collaborator there, and his team, as well as David Goldstein and his team, now at Columbia University, as well as our teams here at HudsonAlpha, said Dr. Myers. "I love this research model because it doesn't happen very frequently, and it really shows how industry, nonprofits, and academic laboratories can all work together for the betterment of humankind. The combination of those groups with a large number of the clinical collaborators who have been seeing patients with this disease for many years and providing clinical information, recruiting patients, as well as collecting DNA samples for us to do this study, were all critical to get this done."

Searching through the enormous database generated in the ALS study, Dr. Goldstein and his colleagues found several genes that appear to contribute to ALS, most notably TBK1 (TANK-Binding Kinase 1), which had not been detected in previous, smaller-scale studies. TBK1 mutations appeared in about 1 percent of the ALS patients--a large proportion in the context of a complex disease with multiple genetic components, according to Dr. Goldstein. The study also found that a gene called OPTN, previously thought to play a minor role in ALS, may actually be a major player in the disease.

"Remarkably, the TBK1 protein and optineurin, which is encoded by the OPTN gene, interact physically and functionally. Both proteins are required for the normal function of inflammatory and autophagy pathways, and now we have shown that mutations in either gene are associated with ALS," said Dr. Goldstein. "Thus there seems to be no question that aberrations in the pathways that require TBK1 and OPTN are important in some ALS patients."

The researchers are currently using patient-derived induced pluripotent embryonic stem cells (iPS cells) and mouse models with mutations in TBK1 or OPTN to study ALS disease mechanisms and to screen for drug candidates. Several compounds that affect TBK1 signaling have already been developed for use in cancer, where the gene is thought to play a role in tumor-cell survival.

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New ALS gene and signaling pathways identified