The VanBrocklin’s are moving forward after Sequencing

As we pass the six-month mark as partners in the iHope program, it has already been so rewarding for us at Rare Genomics to see underserved families receive Whole Genome Sequencing in an effort to gain results and treatments for the conditions of their loved ones. We first shared the VanBrocklin story and video when they received their positive Whole Genome Sequencing results early this year.

I had the opportunity to interview the Van Brocklin family for the video at their home in Racine, Wisconsin, and came away very inspired. After visiting with Jami and Jonathan for just an afternoon, I was taken aback by all of the roadblocks that they have had to overcome in their search for answers for their children, Jasmine and Ronin. Now looking back months after receiving the sequencing results, we can see what a difference they have made.

The cost of copays, prescriptions and therapies for the VanBrocklin’s were well over $5,000 a year; in fact in 2016, they actually hit the threshold ceiling for medical tax deductions. With undiagnosed children, it was very difficult for the Van Brocklin’s to find any answers.  From a financial point of view, most insurance providers do not cover procedures like Whole Genome Sequencing, making it very difficult to acquire the comprehensive testing that is the key to unlocking these genetic secrets. From a parenting perspective, imagine having children with a disease that is unknown. It is impossible to start fighting a disease that you can’t even put a finger on.

Fortunately, both Van Brocklin children were able to take advantage of the iHope program and received results for their diseases. With Jasmine’s confirmed diagnosis for Ichthyosis Vulgaris, she has been referred by the Children’s Hospital of Wisconsin to their new pediatric genetic dermatologist.  This specialist possesses a much more thorough understanding of her condition. In Ronin’s case, with confirmed genetic testing findings of 16p11.2 microduplication he was able to obtain an official diagnosis of Autism. This diagnosis gives the Van Brocklin’s the option of specialized therapy, and also relieved concerns that his symptoms may have been due to a more significant health concern.

Our partners at Illumina, through the iHope program, have done a tremendous job working with us to provide underserved families with Whole Genome Sequencing testing and it has been a privilege of mine to be a small part of it.  If you are looking to be a part of the program, or if you have a family member that may qualify for the iHope program, please do not hesitate to join us in our search for answers.

Richard Bonds

Tenth Annual Rare Disease Day

The last day of February is a day to create awareness and let patients and affected with rare diseases be heard. This year, February 28th marks the tenth year of Rare Disease Day.

Rare Genomics (RG) participated last year, and we will again this year be a part of a day where rare diseases get the attention they deserve. This day patients worldwide stand together and make their voices heard, and RG wants to be a part of this.

What is Rare Disease Day?
Rare Disease Day seeks to raise awareness amongst both the general public and decision-makers about rare diseases and how living with these impacts patients’ lives.

Many different organizations participate in Rare Disease Day events. Rare Disease Day started in 2008 as a European phenomenon - but today it has expanded into be a worldwide phenomenon. Hundreds of patient organizations work to raise awareness for the rare disease community in their countries all year around, but on the last day of February they get extensive public and political attention.

The last day of February was chosen as Rare Disease Day since February 29th is the rarest day and only occurs every fourth year.

The official poster for Rare Disease Day 2017

Join us for Rare Disease Day
Rare Disease Day is an opportunity for RG to draw attention and awareness to rare diseases. The awareness is important in order to hopefully diagnose and cure many more patients with rare diseases in the future.

Please join us and participate in Rare Disease Day! Your donation to RG will help patients living with a rare disease. By donating to RG and being part of the tenth Rare Disease Day you contribute to a brighter future for the patients - a future without rare diseases.

Read more about Rare Disease Day and RG's participation here and donate by clicking the button below. Thank you!

Paper on Orphan Drug Development in China Published

Alice Cheng and Zhi Xie of the Rare Genomics Institute have published a open-access paper, "Challenges in orphan drug development and regulatory policy" in the Orphanet Journal of Rare Diseases.

Orphan drugs are pharmaceutical treatments developed to treat specific rare diseases. They aren't profitable for pharmaceutical companies to produce due to their extremely specific nature. Regulatory policies on orphan drug development are well-defined in the United States and European countries, but rare disease policies in China are still fluctuating. Pharmaceutical companies in China are de-incentivisted to pursue drug development for rare diseases due to a lack of clear definition and regulatory approval process. As a result, many rare disease patients in China pay out of pocket for international treatments.

Many grassroots movements have begun to support rare disease patients and facilitate research for the development of orphan drugs. The Chinese FDA has recently set new regulatory guidelines for drugs being developed in China, including an expedited review process for lifesaving treatments.

Cheng and Xie's paper compares orphan drug development and regulatory policy in China and the US. They find that due to political, economic, and cultural differences, China cannot simply base its policies on the American model. China's public healthcare system has the opportunity to take advantage of available data to create aggregated databases for diseases and genomic information, assisting epidemiology research.

The authors advocate for the five suggestions proposed by the National People's Congress and Chinese People's Political Consultative Conference of 2009:

  1. Establish a definition for rare diseases.
  2. Develop an orphan drug reimbursement system.
  3. Propose a clear and simple approval pathway for imported orphan drugs.
  4. Promte rare disease research through policy.
  5. Develop government-supported programs for rare disease patients.

Read the full paper from the Orphanet Journal of Rare Diseases.

Leading the Way: Marching Onward

At the Rare Genomics Institute, we understand that enacting change cannot happen unilaterally and that solving medical mysteries does not come without teamwork. We stand proudly at the forefront of the utilization of genomic sequencing for the purpose of identifying, treating and hopefully curing rare diseases. At the same time, we realize there are many other people outside of our organization who are just as fundamental to the fight against rare diseases as we are. The team at RG is inspired by those who dedicate their lives to helping others affected by rare disease. Here is one of their stories:

Research is the backbone of scientific discovery. Researchers do not often hone their craft in the spotlight: theirs is a task best suited at the lab bench, away from the public eye. It was, therefore, striking to come across a geneticist who works with the public on a daily basis as a pediatrician in my proverbial backyard at Columbia University. In December of 2016, I sat down with Dr. Wendy Chung to discuss her unique practice.

Dr. Chung holds both a PhD in genetics from Rockefeller University and an MD from Cornell University. The confluence of those pieces of education is not coincidental; “The year that I started my MD/PhD program was the year the Human Genome Project officially started. It became very clear to me that there was going to be a very unique opportunity in terms of being able to harness [that] power.”

Her interest in genetics in tow, Dr. Chung tailored her research and subsequent medical practice toward those who need genetic research most: children with rare diseases.

“A lot of individuals with rare disorders don't live to grow up,” Dr. Chung continued, “[However], it’s just been miraculous to me to be able to see how much things have evolved and changed in a very positive way: What I see now is that getting a diagnosis is much easier than it used to be. Now our energy needs to be focused on developing treatments. What drives me now is to figure out how we can get beyond the diagnosis and get to [those] treatments.”

Setting a Course:

The route that Dr. Chung’s lab takes toward diagnosis and treatment is somewhat irregular. Gene editing has been mentioned on the Rare Genomics Institute’s website before.

However, Dr. Chung edits the genes of model organisms (mostly mice) in order to test the reactions of those organisms to treatments before utilizing suggested treatments on humans. Dr. Chung’s practice is unique in that she and her team participate on both the research and practical implementation sides of the fence. She is actively both testing treatments and treating patients.

Dr. Chung stated, “We do everything we can in terms of clinical care and then we continue to march onward. If we don't find anything we can do clinically we cross over the fence into research mode and do everything we can on the research side. We can return information from the research study to [patients] and hopefully get them to a diagnosis faster and more effectively.”

Dr. Chung continued, “Because Columbia is a research institute, when we identify new conditions, we do our very best to help families connect to each other and to share information amongst clinicians. [We then] make that information freely available and accessible so that we can all learn together and try to understand mechanisms for why these conditions exist.” Dr. Chung detailed some of the limitations of more orthodox research methods, “If you're talking about cells in vitro, it’s a fine model for very basic molecules in terms of how they interact in a cell. But even if you make an organoid in terms of neurons in a dish, you can’t get that to function like a brain does. Maybe if you're lucky you'll get something that looks like a seizure from an electrical point of view, but often times you can’t get anything that approaches the right behavioral difference.”

Researchers at Columbia come to similar crossroads in Dr. Chung’s lab. “When it comes to mice or any other model organism,” stated Dr. Chung, “the mice may look basically fine, but the people, who have this same condition, they are clearly not fine.”

The two halves of Dr. Chung’s practice are united due to this complication. Though rodents inflicted with the same rare conditions as human patients may appear to function normally, Dr. Chung notes that mice do not read or write; they are not responsible for higher-order thinking challenges like those of a human. Therefore, sometimes, modeling is insufficient in both diagnosis and in research for treatment techniques for patients.

Next Steps:

The goal of Dr. Chung’s practice is, of course, not simply diagnosis but treatment. There are limitations to this goal, however. Research timelines often stymie a patient’s journey from diagnosis to treatment. Dr. Chung elaborates, “Treatment isn't something that comes a week after you get the diagnosis. It often takes several years to do that, but we're working with families to take that next step.”

Time is not the only limiting factor in the treatment of a patient living with a rare disease. Costs can be overwhelming for families. Accessibility is extremely important to the rare disease patient community and Dr. Chung’s team certainly recognizes the fact. Dr. Chung notes, “We take all types of insurance, whether it’s Medicaid or private insurance. We try to have enough capacity to try to deal with all of the different types of patients that would come in, whether they're kids or adults.”

“On the other hand,” Dr. Chung continued, “we also try to be realistic. If there are some individuals where, if we don’t think that there's a high enough probability that we're going to find something or help them even if we don't find an answer, we don't have them come halfway around the country.”

Working Together:

Dr. Chung’s patient population is wide-ranging in the geographic sense, and admission therein requires that only 3-5 patients are seen each week. Typical patients of the DISCOVER (Diagnosis Initiative: Seeking Care and Opportunities with Vision for Exploration and Research) Program “tend to be many of the same types of folks that you guys are working with at the Rare Genomics Institute” states Dr. Chung, “[these] kids may have neuro-developmental disorders or congenital anomalies or very rare or very early onset presentations of conditions that increase the probability that [their conditions may be] something hereditary.”

Many of Dr. Chung’s patients are designated “N-of-1” or the very first patients to experience certain conditions. Dr. Chung clarified, “Although it’s not always the case, it’s not unusual for us to be an N-of-1 situation for a while. [These situations] don’t stay N-of-1 for very long, but they often start out that way.”

The uniqueness of her patient’s conditions often leads to frustrations in treatment. Dr. Chung notes that in terms of ultra-rare diseases, the challenges of both time and money weigh heavily on the patient population, “ultra-rare diseases are individually so rare that it is hard to be able to get the resources and the talented scientists to be able to dedicate all their energies for conditions that affect one in two million people, for example.”

Emphatically reinforcing why her organization is important in the many fights against rare conditions, Dr. Chung stated, “Unless every rare disease is blessed with a family who has gazillions of dollars they don't know what to do with, you can get stuck.”

But Dr. Chung’s team needn’t help families get un-stuck alone, “This is very much a partnership. Families really have to take up the cause and push things forward, especially when it comes to the ultra-rare disorders. If they don't, it's not like a lot of people are going to run to their assistance.”

Moving forward from diagnosis is a communal effort: it is up to all of us. Whether you’ve been inspired by the work of artists or you know someone living with a rare disease yourself, the work of doctors and researchers to help patients living with rare conditions cannot be completed without your help. Please consider suppporting ongoing rare disease research efforts. Let's march onward together.

CRISPR and Gene Therapy: An Overview of the Breakthrough Gene-Editing Tool

CRISPR has been in the news lately—for good reason. At Sichuan University, the first human patient is being treated with immune cells edited via CRISPR.

CRISPR has made effective gene therapy a realistic possibility for the near future. But how?

The structure of Cas9, from the National Institutes of Health (NIH).

The structure of Cas9, from the National Institutes of Health (NIH).

Targeting DNA with CRISPR

CRISPR is short for Clustered Regularly Interspaced Short Palindromic Repeats. The long name describes what it is: DNA segments from prokaryotes (single-cell organisms) with a series of short, repetitive base sequences punctuated by spacer DNA that originated from plasmids or phages (infectious agents). Palindromic repeats aren’t like palindromes in language; instead, they are a particular sequence of DNA that, when transcribed, can form a three-dimensional “hairpin” loop in RNA.

CRISPR DNA segments are part of a prokaryotic immune system, the CRISPR/Cas system. When plasmids and phages attack a prokaryote, inserting foreign DNA, this system resists. CRISPR associated proteins (Cas) use the foreign origins of CRISPR’s spacer DNA to identify the newly inserted sequences. Cas then copies these sequences and places them into an RNA molecule. Cas and this RNA molecule comb through the cell to find foreign DNA from plasmids or phages. When a match occurs, the portion of the RNA molecule copied from the spacer DNA locks on, allowing a Cas enzyme—Cas9, an endonuclease—to slice the foreign DNA. Now damaged from broken phosphodiester bonds, the plasmid’s or phage’s DNA can’t replicate within the cell.

The specific CRISPR/Cas system used in biotechnology is engineered from the CRISPR/Cas system in the bacteria that causes strep throat, Streptococcus pyogenes. When people talk about CRISPR, they’re referring to the whole CRISPR/Cas system, not just CRISPR as the DNA segments.

Using CRISPR to Cure

CRISPR can be used in gene therapy to treat diseases with a genetic component. Gene therapy uses genes themselves as a means to prevent or treat diseases. This can be done at a cellular level by inserting healthy genes, making a harmful gene inactive, or replacing a harmful gene with a healthy gene. Gene therapy uses a process called genome editing, which refers to any method that uses an endonuclease (molecular scissors) to cut DNA at a specific location in order to insert, remove, or replace a gene. Cas9’s ability to slice foreign DNA at targeted points makes CRISPR an effective tool for gene editing, and therefore, gene therapy.

When treating disease, scientists program CRISPR to detect a specific sequence that makes up a harmful gene. When that sequence is found, the DNA strand is unzipped and the harmful gene removed. In some cases, the DNA can repair itself. In others, scientists insert a healthy gene into the gap left by CRISPR. Gene therapy that occurs in somatic cells (body cells) facilitates treatment, as the gene’s intended function is restored.

Looking Forward

CRISPR isn’t foolproof, though; sometimes, Cas9 can cut DNA at the wrong place. However, CRISPR’s efficiency and overall accuracy allow it to overshadow earlier gene editing tools, like TALENs (transcription activator-like effector nucleases) and ZFN (zinc finger nuclease). Because of its programmable nature, it only takes a few days to engineer CRISPR to detect a specific sequence of DNA. With CRISPR, both copies of a gene—and both copies of multiple genes—can be edited at the same time.

Despite these qualities that make CRISPR the most efficient gene editing tool yet, both technical and ethical issues compound research. A significant technical hurdle is how CRISPR is delivered into individual cells. CRISPR must have direct access to a cell’s DNA to make repairs.

And even though CRISPR has already been used successfully in crops, mice, and mosquitoes, ethical questions arise when genetic engineering is applied to humans. This type of gene editing still poses risk: the crux of the decision to use gene therapy relies on weighing the risks of a genetic disease versus the risks of its potential cure. Even if ongoing research trials are successful, it will take years for CRISPR-enabled gene therapy to become a fixture of the clinician’s office.

Overall, CRISPR is an accurate and powerful tool revolutionizing how gene editing and gene therapy are approached. As more research is completed, the full potential of this method can be revealed.

Rare Genomics Institute participates in #GivingTuesday again

 

Rare Genomics Institute was a part of the international movement #GivingTuesday last year, and now it is time to attend the international day of giving again. It is a day that brings nonprofits, donors, businesses and communities together celebrating generosity and the impact of giving back.

We are looking forward to participate again this year and fundraise resources, so we can continue and improve our important work on fighting rare diseases.

Last year, thanks to the support of all our amazing volunteers, we managed to raise almost $20,000 dollars between #GivingTuesday and the Year-End Campaign. We are excited about participating again this year, and we are confident that together and with all your help we will be able to meet 2016’s fundraising goal of $25,000 dollars.

The Year-End Campaign is divided in two parts. The first parts is from November 12 until November 29 (#GivingTuesday) and the second part from December 1 until December 31. We count on and hope for your help and the help of your friends and families this year.

Join Rare Genomics Institute’s participation in #GivingTuesday and celebrate generosity worldwide. Together we stand stronger and can make a huge impact. Thank you in advance and have a lovely November!

Leading the Way: Beyond the Diagnosis

Leading the Way: Beyond the Diagnosis

The Rare Disease United Foundation launched the Beyond the Diagnosis exhibit just two years ago. The idea was that portraits of those living with rare diseases could allow people to become more engaged with the rare disease patient community; that there is more to a person living with a rare disease than the diagnosis itself.

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Shooting for the Moon in Honor of Mesothelioma Awareness Day

As Mesothelioma Awareness Day approaches, it's the perfect time to raise awareness about this rare form of cancer and the amazing potential for progress now in sight thanks to the Cancer Moonshot project. Established in 2004, Mesothelioma Awareness Day (September 26th) exists to bring funding and attention to mesothelioma, a rare yet aggressive and deadly form of cancer. So, how much can the Cancer Moonshot do to bring an end to Mesothelioma?

Mesothelioma

Mesothelioma is a rare form of cancer, with only about 2,000 to 3,000 new cases annually in the US. In cases of malignant mesothelioma, cancer cells form in the thin layer of tissue lining the abdomen, chest wall, or lungs, or, less commonly, in the testicles or heart. Long-term asbestos exposure is the primary cause of malignant mesothelioma in adults. This exposure puts not just the person who was originally exposed at risk, but also that person's family members. This kind of malignant mesothelioma typically takes 10 to 40 years to develop after exposure.

Pediatric mesothelioma is different in that it can spontaneously generate and does not necessarily have a link to asbestos exposure. In fact, most cases of pediatric mesothelioma seem to have no apparent cause, making prevention difficult. It is also exceedingly rare, as most cases of mesothelioma are in older adults.

The Cancer Moonshot and Data Siloing

In January of 2016, President Barack Obama announced the Cancer Moonshot project during his State of the Union address. The goal of the initiative is to double the amount of research progress in the fight against cancer by putting more money, cooperation, and focus on the most promising areas; by making more therapies available to more people; and by ensuring that the siloing of cancer research data comes to an end. The initiative is led by Vice President Joe Biden who directs the Cancer Moonshot Task Force; they are advised by the National Cancer Advisory Board (NCAB) and its working group, the Blue Ribbon Panel dedicated specifically to the Cancer Moonshot.

The issues that the Cancer Moonshot have identified are perhaps not surprising to anyone who is passionate about rare diseases generally or a specific rare disease such as mesothelioma. Nevertheless, they are notable and deserve our close attention.

First, the issue of siloing of data, research results, and scientific knowledge generally is a tremendous problem for all sufferers of rare diseases—people who make up about ten percent of the US population. While cancer immunotherapy, combination therapies, and genomics hold incredible promise for patients, siloing means a lack of access and progress.

As of the time the Cancer Moonshot was announced, only about 5 percent of American cancer patients participated in clinical trials for new treatments. Most of them don't have access to their own results and data. Furthermore, most oncologists simply don't have access to the latest advances in treatment research and technology.

Historically, the raw scientific data collected by researchers throughout the course of studies becomes the property of the institutions that the researchers work for. The end result is mountains of data locked away in each individual research institution, but no central repository from which truly groundbreaking conclusions and progress may spring. The need to detect biological and genetic patterns that could reveal the mechanisms that enable cancer to manifest and grow makes sharing and collaboration essential.

The Cancer Moonshot initiative has now identified one of its key goals: the creation of a National Cancer Data Ecosystem. This would be a free “one-stop shop” for research data on cancer available to patients and researchers alike. Patients could upload their own data and in turn receive information about their particular variety of cancer.

Collaboration is also going to be critical for making new treatments like immunotherapy more effective. Currently, only 20 percent of patients get the full benefit of immunotherapy treatments. Researchers hope that by pooling all existing knowledge about immunotherapy treatments and practices more effective forms of immunotherapy might be developed.

This kind of information sharing should also benefit genomics treatment projects such as the Collaborative Cancer Cloud. This project aims to create tailored gene therapies for each patient, and to do that it needs to access huge amounts of data on genetic mutations, cancer surveillance, and treatment effectiveness.

New Treatments Arising from Moonshot Research

In September 2016, the Blue Ribbon Panel reported back to the Vice President with recommendations for the rest of the Cancer Moonshot initiative. The report contains ten suggestions which will form the “research blueprint” for the rest of the project.

Cancer Immunotherapy in Focus

Ideally, the body's natural immune system works to prevent cancer by detecting and destroying cells that are abnormal. However, cancer cells can sometimes avoid being detected and destroyed by the body's immune system. They have several ways of avoiding the defenses of the human immune system:

  • Some cancer cells make it harder for the immune system to see them by reducing the expression of tumor antigens on their surface;
  • Some cancer cells inactivate immune cells by expressing proteins on their surface; and
  • Some cancer cells can both promote their own proliferation and survival and suppress immune response by inducing surrounding cells to release immune suppressing substances.

Knowing these tactics employed by cancer cells, researchers have pursued the field of cancer immunology, which has emerged over the past few years. The new techniques for treating cancer created in this field, called immunotherapies, all have the common goal of increasing the strength of immune responses to tumors. Immunotherapies can do this in several ways, but most methods boil down to countering specific cancer cells that suppress immune responses, providing man-made immune components, or stimulating smarter or stronger immune system responses generally.

So far immunotherapy is more effective against some kinds of cancer than others; for those varieties, immunotherapy alone may be enough treatment. For cancers that are less responsive to immunotherapy, at least so far, immunotherapy can still boost the effectiveness of other treatments when used in combination with them.

Several broader research questions related to cancer immunotherapy remain, and these too will be pursued as part of the Cancer Moonshot initiative:

  • Why is immunotherapy effective in certain patients with one type of cancer but not in others who have the same type of cancer?
  • How can we expand the use of immunotherapy to more varieties of cancer?
  • How can we increase the effectiveness of immunotherapy by combining it with other treatments like chemotherapy, targeted therapy, and radiation therapy?

Kinds of Cancer Immunotherapy

Once you understand the many kinds of cancer immunotherapies already under development, it is easy to see why the Cancer Moonshot experts find this area so promising. Here are the kinds of cancer immunotherapy that exist today.

Adoptive Cell Transfer

In adoptive cell transfer, an experimental form of immunotherapy, some patients with very advanced cancers have been completed cured. These patients primarily suffered from blood cancers. ACT works when T cells from inside the tumor of a patient, called tumor-infiltrating lymphocytes (TILs), are collected. Those TILs are then tested to see which show the greatest recognition of the patient's tumor cells. Those selected are then grown into large populations in the laboratory and activated by cytokines, immune system signaling proteins. Finally, the treated TILs are infused into the bloodstream of the patient.

This works because the most successful T cells are multiplied and put back to work. With greatly increased numbers they can then shrink or even kill off the tumors.

A similar method is called CAR T-cell therapy. This works by collecting T cells from the blood and then genetically modifying them to express CAR, a chimeric antigen T cell receptor protein. Then, as in the other ACT technique the modified cells are grown into large populations and reintroduced into the patient. Once inside the patient, these new CAR T cells attach to the surface of the cancer cells and attack them.

Monoclonal Antibodies to Treat Cancer

The immune system can attack invading substances like cancer cells by manufacturing many antibodies, proteins that sticks to antigens, specific proteins carried by enemy cells. Once so “marked” by the antibodies the entire immune system can get involved and fight the cells that contain that antigen.

Monoclonal antibodies (mAbs) are antibodies designed to target a particular antigen like those found on cancer cells. Scientists can make these mAbs in large numbers in labs, and these can be used to treat some cancers. In fact, more than one dozen mAbs have been approved to treat various cancers by the US Food and Drug Administration (FDA).

Naked monoclonal antibodies are the most common kind of mAbs used to treat cancers. These work without any radioactive material or drug attached to them.

Conjugated monoclonal antibodies, also called labeled, loaded, or tagged antibodies, are joined to either a radioactive particle or a chemotherapy drug so that the mAbs can be used to locate cancer cells and take the treatments directly to them. This helps lessen the damage caused by these treatments to healthy cells.

Radiolabeled antibodies are joined to small radioactive particles. These are used in radioimmunotherapy (RIT). Chemolabeled antibodies, also called antibody-drug conjugates (ADCs), are mAbs that carry drugs, usually chemotherapy drugs. Both of these are types of conjugated monoclonal antibodies.

Bispecific monoclonal antibodies are drugs that contain two different mAbs; this allows them to attach to two different proteins simultaneously.

Some therapeutic antibodies bind to cancer cells and cause apoptosis or cell death. In other cases, the binding antibody is recognized by specific immune cells or proteins, which then cause the cancer cells to die by cytotoxicity.

Immune Checkpoint Modulators

Obviously, to work properly the immune system must be able to distinguish between normal, healthy cells and “invader” cells. It needs “checkpoints” to do this. Checkpoints are molecules on some immune cells that must be activated or inactivated in order to prompt an immune response. Cancer cells can sometimes avoid or use these checkpoints to avoid detection or attack; this is why treatments that target checkpoints are promising.

There are two kinds of cytokines, proteins that normally modulate or regulate the activity of the immune system, that are being used to enhance the human immune response to cancer: interferons and interleukins. Some of these proteins activate white blood cells like dendritic cells and natural killer cells.

Researchers are also working to develop more drugs that target checkpoint proteins on T cells such as PD-1 or PD-L1. These checkpoint proteins act as “off switches” for the immune system and are intended to protect healthy cells. However, these are also found on some cancer cells, a defense mechanism against attack.

Benefits of Immunotherapy

Cancer immunotherapy offers some clear benefits. First of all, it has the potential to fight many different types of cancer. Because it enables an effective response from the human immune system, effective immunotherapy would provide a universal cure for cancer. Immunotherapy is already effective against many varieties of cancer, including some that have resisted traditional treatments like chemotherapy and radiation (melanoma, for example).

Effective cancer immunotherapy is more likely to produce long-term cancer remission because it “trains” the immune system to fight and remember cancer cells. Longer lasting remissions could well be the result of the human “immunomemory.” Furthermore, many clinical studies on cancer immunotherapy have already demonstrated long-lasting beneficial results.

Cancer immunotherapy is less likely to produce as many terrible side effects as chemotherapy and radiation do. This is because it is more targeted and protective of healthy cells. Typical immunotherapy side effects resemble the symptoms of fighting off infection, such as fever, inflammation, and fatigue, although some immunotherapy carries with it more severe side effects mimicking symptoms of autoimmune disorders.

In all, the potential benefits of successful cancer immunotherapy are tremendous.

Conclusion

On the eve of the 12th Mesothelioma Awareness Day, the Cancer Moonshot has provided a new sense of hope and progress. With its focus on cancer immunotherapy and enhanced cooperation and access to information, the Cancer Moonshot reveals an intelligent approach that has an ambitious yet realistic goal. Mesothelioma awareness advocates hail the Cancer Moonshot as a commitment even to rare forms of cancer that are often overlooked, because the benefits are clearly going to be felt by our community.

From a rare disease perspective, the Cancer Moonshot model is particularly appealing. Will a success in this area provide a new paradigm for a more collaborative fight against rare diseases in the future?

Karla Lant is a freelance writer and editor who volunteers for the Rare Genomics Institute.

Rare Genomics is a finalist for the 2016 Drucker Prize!

The winning nonprofit organization, which receives a $100,000 grant, will be announced on September 30. The Rare Genomics Institute was selected from 50 semifinalists—out of 500 applicants—after completing mini-courses that covered innovation and nonprofit performance. Rare Genomics answered questions on our current organizational practices and how we could implement the new ideas that were presented through the mini-courses.

The Drucker Prize, formerly known as the Peter F. Drucker Award for Nonprofit Innovation, has been awarded since 1991. Winning organizations represent the Drucker Institute's definition of innovation: "change that creates a new dimension of performance." Nonprofits are judged on effectiveness, the difference their programs can create in the lives of people they serve, and their innovative impact.

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BeHEARD 2015 Winner Update: Progress on Rare Skin Disorders

Heather Etchevers, a research scientist at the French National Institutes of Health, is a two-time winner of the BeHEARD competition for support for her research on identifying mutations that lead to giant congenital melanocytic nevus (CMN), a pigmented birth defect of the skin that requires surgery to remove.

In 2013, Heather was selected to receive a supply of JumpStart TAQ ReadyMix, a PCR reagent, from Sigma Life Sciences, which led to her lab finding the mutation responsible for CMN in eight patients. Heather was also able to use leftover reagent supplies for ongoing research to identify the genetic cause behind a second rare disease, cutaneous arteriovenous malformations. Her lab was able to eliminate one of four likely genes as a potential cause, a result that was written up for journal publication. During 2015, Heather was awarded $10,000 worth of existing mouse models from The Jackson Laboratory’s live repository, from which she selected six defined lines.

Heather and her team, “…are looking forward to using a so-called reporter mouse strain to monitor the activation of a particular signaling pathway in individual cells. With the animal model and cellular tools we are developing at the moment, [we will] develop innovative approaches to curing the worst effects of CMN syndrome (cancer, neurological deterioration) and managing the ones with psychosocial impact, such as a strikingly different appearance, relentless itchiness or otherwise less than fully functional skin.”

"It's always a tremendous challenge to attract research funding for rare diseases - even more so when we are carrying out fundamental studies in mechanisms and causes", says Heather. "RGI BeHEARD did just that - the fact that an award was attached made our research more visible and attractive for other funders."

DNA Dash

Rare Genomics Institute Calgary Executive Vyoma Shah talks about her personal experience with RGI and the DNA Dash in an interview with Global News Calgary.

BeHEARD 2015 Winner Update: Progress on Opitz C Syndrome

Dr. Roser Urreizti is a postdoctoral fellow at CIBERER, Universitat de Barcelona (Spain). Roser’s work focuses on searching for the gene or genes responsible for Opitz C Syndrome, by means of whole exome sequencing and functional studies. One of the distinguishing features of C Syndrome is a condition in which the skull is a triangular shape, primarily due to premature closure of the cranial sutures. The disease is also characterized by mental retardation, loss of muscle tone, abnormalities of the sternum, facial palsy, webbed fingers and/or toes, contractures, short limbs, heart defects, failure of one or both testicles to move down into the scrotum, (cryptorchidism), abnormalities of the kidneys and lungs, deformity of the lower jaw, and seizures.

In the 2015 BeHEARD Competition, Roser was awarded whole exome sequencings from Euformatics, which allowed her team to confirm that they had found the genetic cause behind the disease.

“In the patients analyzed by the Euformatics platform, we have identified the disease-causing mutation,” says Roser. “We have already started functional studies for every one of the genes associated with the diseases. None of them had been previously associated with Opitz C syndrome. We hope we will be able to test therapeutic approaches (molecular chaperones) in one year in a near future. We have started a collaboration to test selected FDA approved drugs on a patient's cells in a search for therapies once the functional studies confirm the relation between the mutation and the disease.”

Three Tips for Crowdfunding for Medical Expenses

With the high cost of medical care in the U.S., an unexpected medical crisis or diagnosis can be disastrous for many Americans. When Americans were asked in an NBER study if they could come up with $2,000 to meet an unexpected expense within a 30 day time frame, nearly half said no. With the rise of the internet to conduct business virtually, crowdfunding through personal networks has become an important tool for people facing crushing medical bills. In fact, one study found that the rise in crowdfunding campaigns was directly correlated with a 3.9% reduction in medical bankruptcies in the U.S. in 2014. While crowdfunding may seem straightforward, there are many different steps you can take to maximize your donations. Here are three strategies that we teach as part of our Amplify Hope training program that may not be obvious to the novice crowdfunder.

Start with some money

Sure, if you had a ton of money lying around, you wouldn’t be crowdfunding in the first place. But seeing that others have donated sends a signal to potential donors that a campaign is legitimate and has a chance at success. In our Amplify Hope study question, “How important is it for you to fund crowdfunding projects that have already received substantial donations from others?” most donors (77.8%) responded that it was at least moderately important, indicating that social recognition and the performance of campaigns is a key factor in the decision to donate. Furthermore, respondents were asked “How important is it to fund projects that are close to meeting their fundraising goal?” and 85% responded moderately to very important.

This phenomenon is supported by other research as well: a 2013 study found that donors on Kickstarter were much more likely to support projects that were near their goals, viewing these projects as more likely to be successful, and that nearly all projects on Kickstarter that reached 50% of their fundraising goal were eventually fully funded.

At RG, we advise all of our crowdfunding patients to try and raise 20% of their goal prior to a campaigns “official” launch day, so that when their campaigns launch, it creates the impression that the campaign is already well on its way to success. This can be done through putting a portion of your own money in the campaign, or by contacting people who you already know are likely to donate (mom, dad, grandparents) and asking them to make their donation ahead of the official launch.

Post a video

A video may seem like a lot of effort, but not having one could hurt your campaign. A study found that not having a video decreased a campaign’s chance of success by 26%. In RG’s Amplify Hope study, all of our successful campaigns posted both a campaign video and several photos. While it’s up to you how much you are comfortable sharing, in RG’s experience, there is no such thing as providing too much information. New content, like videos, photos, and updates gives you an excuse to repost the link to your campaign to your entire network, and keeps donors, or those who may be considering donating, engaged with the campaign. Other research also backs this up, demonstrating that updates serve as “legitimizing signals” to potential donors that campaign managers are committed to the process and likely to use the money wisely, and that successful projects usually had a public or private update near their campaign’s target end date.

Use Facebook, but don’t forget more traditional outlets

Studies by multiple authors agree that having a large number of friends on online social networks is correlated with successful crowdfunding campaigns. In our study, most donors heard about our participants’ crowdfunding campaigns through social media (61%). Of those that responded that they learned about the campaign through social media, 89% of them found out through Facebook, which might lead you to conclude that Facebook is a good place to focus efforts.

However, our study also found that contribution amounts from donors who were approached via word-of- mouth, email, and phone were substantially higher than those from donors contacted through social media. Additionally, individuals in our study who had the best fundraising outcomes did not necessarily have the most actively shared posts or more visitors to their crowdfunding page (as the “click rates” have indicated). Rather, these organizers followed our training materials’ recommended guidelines, and initiated communication via phone calls and emails to their network. While social media can help you cast a wide net, a personal appeal through more traditional outlets can actually help you raise more money, and get the word out to people who are not social media users or who check infrequently and might miss your updates.

Leading the Way: Positive Exposure (Part Two)

At the Rare Genomics Institute, we understand that enacting change cannot happen unilaterally and that solving medical mysteries does not come without teamwork. We stand proudly at the forefront of the utilization of genomic sequencing for the purpose of identifying, treating and hopefully curing rare diseases. At the same time, we realize there are many other people outside of our organization who are just as fundamental to the fight against rare diseases as we are. The team at RG is inspired by those who dedicate their lives to helping others affected by rare disease. Here is one of their stories:

Last time we began to showcase a remarkable individual whose chosen path in life is to convince the world that all people are beautiful. Rick Guidotti creates positive imagery where others choose to ignore it: his photographs allow the viewer to realize that everyone, no matter their disability or condition, is beautiful.

Beautiful Light:

This does not come without its challenges. Before photographing those with Fragile X Syndrome (a genetic marker for Autism), Rick did not know that those with the disease prefer not to look into other people’s eyes. When attending an event with the hopes of photographing some children with Fragile X, Rick was surprised when many of the children ran away from him screaming.

Looking into a camera was apparently a scary experience for these children. In an effort to remedy the situation, Rick began photographing a little girl’s doll and showing her the pictures. Giggling, she brought Rick all of her dolls to photograph. After running out of dolls, the girl showed Rick her friends at the event, and then her family. Eventually, Rick had photographed everyone in the room.

Rick’s technique in photographing his subjects (or as he refers to them, “Ambassadors”) should be noted:

(I) just turn the light on these amazing people that normally don't have a light shined on them and they're usually beaming. So many times it’s not just the person that’s beaming on the set, it’s their families that are off set that are beaming even brighter: their kids are finally being seen the way that they should be…People have so much to offer, no matter what their capacity happens to be, the joy is in there. That's what we need to see. There isn't anybody that should never be seen in that beautiful light. We should all be seen in that light. That's what Positive Exposure is about: to make sure that everybody, everybody has that opportunity.

Faces Redefining Medical Education:

Medical textbooks and training materials are in dire need of more humanized photos of people living with disease. Most imagery found in those materials is stark: it is designed to show the (often literally) naked and harsh reality of physical deformity. It ignores that those living with diseases are people, rather than objects. In designing photographs to show simply how a disease presents itself, the makers of medical texts often ignore the human element in their pictures.

Through Positive Exposure’s FRAME (Faces Redefining Medical Education) program, Rick is working with the medical community to re-craft ideas of what an appropriate image can be in a medical model.

Rick began his work on the FRAME project highlighting Marfan’s Syndrome, “I thought, as an artist, how can I present Marfan's Syndrome (with) all the information you need as a healthcare provider in training to identify Marfan's, but let’s add the most important, key ingredient which is missing in all these photographs: humanity.”

The reason for the FRAME project is simple, “Nobody, and this is across the board; nobody wants to be seen as a disease or diagnosis. We always want to be seen as a person, first and foremost. (We) also have an opportunity to see all of these great Ambassadors the way someone that loves them sees them: through the eyes of their mom or dad, through the eyes of their partners or their children or their siblings or their best friends.”

The FRAME project doesn’t end at still photographs, however. FRAME’s foundation is a series of short videos (around 10 minutes in length) that highlight the hallmarks of a disease or condition. The twist that makes these instructional videos more impactful than most: they’re told from the perspective of either someone living with (or a loved one of someone living with) a particular disease or condition.

The impact of these much more personal experiences cannot be overstated, “senior physicians have never even heard of some of these conditions before. But med students can get seven minutes where they can learn from Winnie, what these conditions are, and (they’re) going to remember it…They're going to be better healthcare providers because they saw these kids not in the clinical environment. They met these kids being kids. They met these kids not in crisis.”

Pearls Project:

Positive Exposure has taken the sentiment of the FRAME program one step further with a project simply titled, “Pearls.” It is clear that not only the medical community, but rather society at large, could benefit from a fuller understanding of each of its members. In collaboration with the Museum of Tolerance, Positive Exposure has facilitated an in-person/online hybrid educational opportunity for children and young adults so that people may begin to understand the differences among themselves.

In the program, Positive Exposure’s Ambassadors share their unique perspectives in life with others who may have questions. These Ambassadors speak about their differences, but they also facilitate more casual conversation: all in an effort to bring awareness to the community at large that our differences in a way make all of us the same.

Pearls has been particularly well-received, according to Rick, “People are just embracing (it) because (Ambassadors) are giving people an opportunity to not look away… (The) Pearls project and all of our other programs are creating opportunities to steady the gaze of the public long enough so they can see beauty in difference and then, of course, to see around that (difference).”

Moving Forward:

From April 5th through April 12th, the Art Director's Club in New York City hosted a Positive Exposure's Spring Gala. That event serves as a model for the organization's future publically. Rick is determined to feature both the FRAME and Pearls projects in future exhibitions, with an eventual eye at integrating each program into American educational programs.

It is important to not lose sight of the reason for the existence of Positive Exposure: the celebration of life and beauty, in all of its forms.

As I personally struggled to define beauty, Rick stated elegantly, “We all have our own ideas of what beauty is. In most of us though, unfortunately, it’s already been defined by somebody else's standard…Beauty is personal. Beauty is something we all should be empowered to see, and we should all be allowed the freedom to embrace our own ideas of what's beautiful.”

Hopefully through Positive Exposure, we can change how we see beauty: just imagine how much we could change.

The Might of the Mights: Parents Overcome Genetics to Save Son

The Might of the Mights: Parents Overcome Genetics to Save Son

Whole-exome sequencing and his parent’s unwavering tenacity finally led Bertrand Might, now almost 7, to a diagnosis—an extremely rare genetic disease (only 18 other diagnosed cases in the world) called N-glycanase deficiency, or NGLY1 for short.

It all began when Bertrand was around 1 month old and his parents Matt and Cristina noticed he was “jiggly” and was seemingly under duress most of the time. By 6 months, he had little to no motor control and Matt and Cristina knew something was very wrong with their son, describing their emotions as fear— visceral fear. “Parents naturally have high hopes for their children,” Matt says and “To have those hopes clawed away in slow motion is devastating.”

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