ALS Research Update from New York Genome Center Scientific Director and CEO – Dr. Tom Maniatis

From donations raised through the ALS Ice Bucket Challenge, The ALS Association, in partnership with the Greater New York Chapter, made a $2.5 million commitment to the Center for Genomics of Neurodegenerative Disease (CGND) at the New York Genome Center (NYGC). This commitment, combined with a matching gift from the Tow Foundation, was one of the driving forces supporting the NYGC’s ALS research program in 2014. Three years later, the NYGC’s CGND has made enormous headway in the ALS genetics space and has become one of the major leaders in the field. Their accomplishments are broad in that they have sequenced and analyzed hundreds of ALS DNA samples, while pairing this information with patient clinical history and more. We are pleased to note that Tom Maniatis, PhD, one of the NYGC’s original founders and renowned ALS researcher, was recently appointed Scientific Director and Chief Executive Officer of the NYGC.

For part II of our NYGC progress update, today we sat down with Dr. Maniatis to learn how ALS Association donations impacted the NYGC over the years and his vision for the Center’s future.

Thank you Dr. Maniatis, for taking the time to sit down with us today and congratulations on your new position as Scientific Director and CEO of the NYGC. I know you have a long history with The ALS Association. Can you tell us about that and how you got involved in ALS research?

Over 20 years ago, my sister was diagnosed with ALS. Soon after her diagnosis, I was approached by Robert Abendroth, one of the original founders of The ALS Association, about the possibility of chairing a committee whose objective was to attract scientists doing basic research, like myself, into ALS research. At the time, ALS research was dominated by clinicians, which is important, but there was an element of basic cutting-edge research that was missing from The ALS Association research program. I came onboard and chaired the committee with Robert. Together, we brought in basic research scientists, and ideas emerged, programs were generated, and funds were provided. Things really started moving. However, it became clear that in order for this program to become successful, it required a full-time scientific research administrator. That was when Dr. Lucie Bruijn was recruited to help run The ALS Association research program. I worked closely with her over many years to develop and expand The ALS Association’s research committee and programs. The earliest advance was to focus on ALS genetics, which clearly influenced my decisions about helping to establish the NYGC later.

How did ALS research get established at the NYGC?

When I first came to New York in 2010, I had already worked on trying to understand the interactions between astrocytes (i.e. neuron support cells) and neurons, which was funded by The ALS Association. We were working on mouse stem cell differentiation into motor neurons and then later human stem cells. We also studied how gene mutations affected transcription and gene expression. This is an area where I worked much of my life. At that time, the genomic methods were just being developed. It became clear the infrastructure needed for this type of work did not yet exist in New York, so there was relatively little activity in genomics. I reached out to the scientific leadership in New York and was pleased that everyone had the same concern and a common desire to establish a robust genome center in New York City. Our institutional founding members, comprised of the top academic leaders, came together in 2011. The institutional founding members of the genome center provided startup financial support and an agreement to serve on the NYGC Board of Directors. That is how we got started. It was a consequence, in a very direct way, of my interest in ALS.

How has ALS Association funding support impacted the NYGC?

The ALS Association contribution of $2.5 million and the matching grant from Leonard Tow and the Tow Foundation made it possible for the NYGC to create the infrastructure to establish a unique global ALS Consortium. This landmark initiative is defined by data sharing, having common Internal Review Board procedures, including patient consent forms, and an agreement to collaborate in generating and analyzing ALS genomic data. Lucie recently commented on how unusual it was to see something this vibrant and internationally connected come together so quickly. That was really our goal.

Do you have a message for our donors that made this support to the NYGC possible?

I believe that the approach we are taking is fundamentally important for ALS research, as it provides the infrastructure for ultimately developing effective treatments for ALS. We got this important initiative off the ground, but it, of course, requires continued funding. The more patients we can sequence, the more information we are going to have. The cost for each patient for whole genome sequencing is significant. Supporting the framework and infrastructure that allows us to continue this is very important. We must continue to raise funds to keep this initiative going. There is always a threat of not being able to fund it, and as a result, lose the momentum in this program. So, that is the message – to emphasize the importance of the continuity of financial support for the NYGC’s work in ALS research. The ALS Association’s investment in this research will help fulfill our joint mission to better understand the mechanisms of this devastating disease and discover new therapies and therapeutics to improve the lives of ALS patients.

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Sequencers at the New York Genome Center

What do you see as the future of the NYGC?

There are three main areas that we are currently focusing on: ALS, cancer genetics, and autism. There is actually some symmetry in these three research programs. The one you know about is in ALS, which is a consortium-based effort to collect genomic data of ALS patients, along with their clinical data. The goal is to harmonize this information in a way that one can explore the nature of the effects of ALS mutations. Dr. Hemali Phatnani leads this program. Her NYGC laboratory and the Center for Genomics of Neurodegenerative Disease, reflect our primary objective – to have consortium based aggregation of clinical and genomic data. We use this data to better understand ALS disease pathways utilizing cutting-edge genomic technology and disease models. That is our major effort at the NYGC.

There is also a symmetric effort going on at the NYGC in cancer genetics. Here we are working with Drs. Harold Varmus, Charles Sawyers, and all of the institutional members of the NYGC, with the goal of establishing a large-scale, shared database of genomic and clinical cancer data. The NYGC excels at generating data and one of our real strengths has been in genome sequencing. I think we are recognized as one of the major players in the whole genome sequencing. Because of our unique expertise, we were awarded a prestigious Center for Common Disease Genomics grant from the National Institutes of Health. Obtaining this award was significant, considering we were only in operation for two years at the time.

This grant supports our research program in autism. Because of the cooperation with the Simons Foundation and two of the top geneticists in autism – Drs. Evan Eichler and Michael Wigler – this is a major program at the NYGC. We are also in discussion with various neurologists in the city about establishing a similar program in other neurodegenerative diseases. Our overall objective is to be an intellectual and data center for these major disease areas and enable the New York scientific community to use genomic approaches to study disease pathways, which we obviously feel is required to develop drugs to treat these diseases.

Thank you for taking the time to sit down with us today to share the NYGC story and your vision for its future. We look forward to hearing the many more great successes targeting ALS coming out of the NYGC!

Read part I of our interview on October 6, 2017 featuring NYGC CGND Director, Dr. Hemali Phatnani.

For more information about the New York Genome Center, click here and here.

Article originally written by the ALSA National Office

A Patient Advocate and Doctor’s Perspective on Clinical Trials: Update on the Retigabine Phase II Trial

Last week, Dr. Brian Wainger of Massachusetts General Hospital and Stephen Winthrop, Chairman of The ALS Association Board of Trustees, gave their unique clinical trial perspectives during the Northeast ALS Consortium (NEALS) webinar titled, “Retigabine Clinical Trial Update & Discussion with ALS Patient Advocate Stephen Winthrop.” For many years, The ALS Association has proudly partnered with NEALS to run ALS centered webinars to disseminate the most up-to-date information to the ALS community. Today’s post discusses the actively enrolling Retigabine clinical trial, which The ALS Association funds, as well as an honest perspective on what it is like to participate in ALS clinical trials.

 

Patient advocate and a championed NEALS Research Ambassador, Stephen Winthrop (pictured LEFT), joined the discussion to give his thoughtful perspective of clinical trial participation. Stephen was diagnosed with ALS almost four years ago and has been involved in over 12 ALS clinical trials – both observational (does not test a drug) and interventional (tests a drug), including the Retigabine study. The decision to participate in a clinical trial is a complicated question with arguments for and against. Stephen provides honest insights on the pluses and minuses of clinical trial involvement, while giving real life examples of some of his experiences.

“The quality and the experience will vary depending on the test and the individuals you are working with. It is a big question of fit,” Stephen explains.

He goes on to state, “The only way we are going to beat this awful disease is by finding a cure and one small way I can do that is by participating in clinical trials. Yes, it involves a needle stick and yes it takes a little time out of your day, but it is worth it. You are helping.”

Dr. Wainger (pictured RIGHT), one of the Principle Investigators of the Retigabine phase II clinical trial, gave a brief trial overview and update. The Retigabine trial is a double-blinded, placebo-controlled study to test the drug as a potential treatment for people living with ALS. The trial is actively recruiting at 12 sites in the U.S. The primary goals are to measure the effects of Retigabine on upper and lower motor neurons (i.e. the cells that die in ALS) physiology in people with ALS and evaluate safety outcomes.

During the first part of the webinar, Dr. Wainger explains the trial clinical rationale and goes over the study in detail including the goals, inclusion/exclusion criteria, the study timeline and what the study requires from its participants. The goal is to enroll at least 30 more ALS patients into the trial as soon as possible.

Watch the webinar here for all the detailed information.

The trial focuses on hyperexcitability of motor neurons. It was previously shown that people living with ALS have motor neurons (both upper and lower) that fire too many signals, meaning they are hyperexcitable. Too much firing leads to motor neuron damage. Retigabine is designed to reduce the over firing of motor neurons.

To physiologically test motor neuron hyperexcitability in trial participants in real time, the investigators use techniques called transcranial magnetic stimulation (TMS) and nerve conduction studies. These specialized tests are a way to measure the connections between motor neurons and muscles. TMS works by stimulating the motor cortex (part of the brain that controls muscle movement) with a magnet and records the response of the muscles in the hand. Nerve conduction studies evaluate the ability of motor neurons to conduct signals to muscles. An important secondary outcome of this study is to determine the potential for the use of these techniques for future ALS trials.

Stephen explains, “What they were trying to do using TMS, which looks like a ping pong paddle held above my head, was to try to make my right thumb to twitch by increasing the magnetic field. No pain was involved to see if my thumb twitched or did not twitch.”

One unique aspect of the Retigabine clinical trial to highlight is that each trial participant will donate a blood sample to be made into induced pluripotent stem cells (iPSCs). These iPSCs are then made into motor neurons in a dish, which reflect the exact genetic makeup of the person they were derived from.

The effects of Retigabine on patient derived motor neurons will also be tracked and compared to the impact of the drug on the patient. This is the first ALS clinical trial to attempt this type of comparison, which has potential as a prognostic and diagnostic tool. Patient derived iPSCs could even possibly predict how a subgroup of ALS patients respond to a drug, which would improve clinical trial design and recruitment.

Stephen adds, “There are so many aspects of this study that is adding to the knowledge base that Brian and his colleagues around the country and around the world are using that plant seeds for clinical successes in the future.”

“One of the things I have said about participating in a clinical trial is that when you are in a room with someone with ALS, do not forget about the human dimension of what you are looking at here. Don’t forget to say to a potential participant, ‘I am sorry that you have been struck by this awful disease,’ and just let that pause. Don’t forget to say, ‘Thank you or thanks for your small part.’”

“In my own experience, those seemingly routine personal touches go a long way, because in the end I do think their decision to participate is fueled in part by just a little whisper of a hope that this will maybe help me. The bigger piece is that you, as a participant, are part of an army of people – I truly believe – will bring an end to this disease.”

We are thankful to Stephen for giving his honest perspectives and we value his dedication to the fight against ALS. With passionate, committed physicians, researchers, clinic staff, allied professionals and especially clinical trial participants – both living with ALS and healthy – all working together in clinical trials, we are many steps closer to a cure.

Watch the full webinar here.

For more information about the Retigabine trial visit the NEALS trial siteand clinicaltrials.gov #NCT02450552.

Senate Passes 21st Century Cures Act, December 7th

Senate Passes 21st Century Cures Act

Yesterday, the Senate passed the 21st Century Cures Act, sending the groundbreaking legislation to President Obama’s desk for a signature. The new law will provide billions of dollars to help accelerate the discovery, development, and delivery of promising new treatments by funding research and streamlining the drug review process. Importantly, the bill also will help preserve access to complex rehab technologies (CRT) power wheelchair accessories.

The 21st Century Cures Act is groundbreaking legislation that has taken over two years of negotiations. Thank you to all of the ALS Advocates who wrote letters, made phone calls and spoke to legislators about the legislation. Because of your hard work, ALS Association priorities were included in the final legislation. Continue reading Senate Passes 21st Century Cures Act, December 7th

The ALS Association and Prize4Life Announce Five Finalists for $400K Assistive Technology Challenge

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November 22, 2016
The ALS Association and Prize4Life announced today the five finalists for the ALS Assistive Technology Challenge, a $400,000 award for the development of flexible, accessible technology to help people with ALS communicate with ease. The winner of the challenge will be selected in Dublin, Ireland, on Monday, Dec. 5 at the International Symposium of ALS/MND.

“Each one of the five finalist groups took a unique approach for tackling the challenges facing people living with ALS. We are very excited about these innovative and groundbreaking technologies and are confident that any one of them has the potential to make a significant impact on the quality of live of people living with ALS and their families and caregivers,” said Maya Bronfeld, Ph.D., Prize4Life Scientific Officer. Continue reading The ALS Association and Prize4Life Announce Five Finalists for $400K Assistive Technology Challenge

ALS Gene C9orf72 Study Published in Journal “Neuron”

Pictured above: Dr. Gao’s laboratory team

A new disease pathway for C9orf72-related ALS was revealed in journal Neuron in a study led by principle investigator Dr. Fen-Biao Gao from the University of Massachusetts Medical School in Worcester, Mass. The research team found that the C9orf72 expansion leads to DNA damage, signifying another potential ALS therapeutic target. The ALS Association supported this encouraging study that also included current and past Milton Safenowitz Postdoctoral Fellows Dr. Dejun Yang (2015 recipient) and Dr. Helene Tran (2012 recipient).

Continue reading ALS Gene C9orf72 Study Published in Journal “Neuron”

ALS Gene C9orf72 Damages DNA Revealing a New Disease Pathway

The most commonly inherited gene in familial ALS, C9orf72, points to DNA damage causing oxidative stress, according to a new study funded by The ALS Association. The study was published in the journal Neuron and led by principle investigator Fen-Biao Gao, Ph.D. and first author Rodrigo Lopez-Gonzalez, Ph.D. from the Department of Neurology at University of Massachusetts Medical School in Worcester, Mass. Findings from this paper point to DNA damage as a disease pathway of C9orf72-related ALS.

Continue reading ALS Gene C9orf72 Damages DNA Revealing a New Disease Pathway

New Protein Target Emerges for C9orf72 the Most Common Genetic Form of ALS

research news banner 2015Targeting a single protein, called SUPT4H1, reduces the levels of the three toxic entities created by the C9orf72 gene expansion, the most common genetic cause of ALS, according to a study published in the journal Science. The finding suggests that SUPT4H1 may be a promising candidate for therapy development for people whose disease is caused by expansion of the C9orf72 gene. The study was supported by The ALS Association and led by senior investigators Leonard Petrucelli, Ph.D., of the Mayo Clinic in Jacksonville, Fla and Aaron Gitler, Ph.D., of Stanford University in Stanford, Calif., along with co-lead investigators Nicholas Kramer, Ph.D., Yari Carlomagno, Ph.D., Fen-Biao Gao, Ph.D., and Yong-Jie Zhang, Ph.D.

Continue reading New Protein Target Emerges for C9orf72 the Most Common Genetic Form of ALS

Hear ALS Association Chief Scientist Lucie Bruijn, PhD, MBA Speak About ALS Research

Towards therapies for ALS: How ALS Association funded research can impact progress

Tuesday, June 28, 2016 | 6:30 p.m. – 8:30 p.m.
The New York Genome Center,
101 Avenue of the Americas, (bet. Grand & Watts Streets), NYC

Register Here

Meet the speaker, networking and refreshments to follow.

Bio: Lucie Bruijn, PhD, joined The ALS Association in January 2001 and is currently the Chief Scientist. Prior to that Dr. Bruijn led a team at Bristol Myers Squibb developing in vitro and in vivo model systems for neurodegenerative disease. Read more.

Talk Abstract: Over the past several years thanks to increased investment and advances in technology, gene discovery for ALS has grown exponentially and with this the opportunities to develop therapies for this devastating disease. Read more.

The Evening Talks Series is sponsored by The Pyewacket Fund of the New York Community Trust.

New C9orf72 Mouse Models Show Neurodegeneration from Most Common Genetic Cause of ALS

research news banner 2015Two independent research studies both funded by The ALS Association, including principal investigator Laura Ranum, Ph.D., of the University of Florida in Gainesville and the other study led by Don Cleveland, Ph.D., of University of California San Diego in San Diego and Clotilde Lagier-Tourenne, M.D., Ph.D., of Massachusetts General Hospital in Boston, have developed new mouse models of the C9orf72 mutation that show neurodegeneration and motor and cognitive deficits reminiscent of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). In addition, one group showed that these effects could be ameliorated in mice by antisense therapy against the mutant gene.

“These studies represent significant progress in understanding the consequences of the C9orf72 gene mutation and in developing a therapy against it,” said Lucie Bruijn, Ph.D., M.B.A., Chief Scientist for The ALS Association.

Continue reading New C9orf72 Mouse Models Show Neurodegeneration from Most Common Genetic Cause of ALS

Innovative ALS Imaging Biomarkers Come Closer to Patients

research news banner 2015The Neurological Clinical Research Institute (NCRI) imaging team at MGH, led by Dr. Nazem Atassi, used PET imaging to successfully scan the first person living with ALS to measure inflammation in the brain, a promising first step in this imaging biomarker study. The ALS Association together with The ALS Finding A Cure (ALSFAC) Foundation, a program of the Leandro P. Rizzuto Foundation, funded investigators at Massachusetts General Hospital (MGH), Houston Methodist Hospital and GE Healthcare to develop biomarkers that would help with diagnosis of ALS and measuring the progression of the disease. The goal is to develop novel MRI and positron emission tomography (PET) imaging tools.

Continue reading Innovative ALS Imaging Biomarkers Come Closer to Patients