Gastroenterology
Increasing stress levels,
unhealthy diets, and a growing senior population are some of the
reasons behind the widespread prevalence of gastrointestinal
disorders. According to a 2013 survey, 74 percent of Americans
live with some sort of gastrointestinal discomfort, which, in
many cases, can be the symptoms of more serious, underlying
conditions.
Diseases of the digestive
system are the domain of gastroenterology, an increasingly
dynamic field for medical innovation. The present article will
review recent trends in gastroenterology and discuss how R&D
tax credits can help support those investing in this promising
field of research.
The R&D Tax Credit
Enacted in 1981, the Federal Research and Development (R&D)
Tax Credit allows a credit of up to 13 percent of eligible
spending for new and improved products and processes. Qualified
research must meet the following four criteria:
New or improved products, processes,
or software
Technological in nature
Elimination of uncertainty
Process of experimentation
Eligible costs include
employee wages, cost of supplies, cost of testing, contract
research expenses, and costs associated with developing a
patent. On December 18, 2015 President Obama signed the
bill making the R&D Tax Credit permanent. Beginning in
2016, the R&D credit can be used to offset Alternative
Minimum tax and startup businesses can utilize the credit
against payroll taxes.
Gastroenterology: An Overview
Gastroenterology is the branch of medicine dedicated to the
digestive system and the disorders affecting the
gastrointestinal tract (stomach and intestines) as well as
accessory organs of digestion. Digestive disorders are among the
most pressing public health issues worldwide. Affecting millions
of people, diseases of the digestive system put a major burden
on national healthcare budgets and cause significant decreases
in patients’ quality of life.
According to the most
recent data by the National Institutes of Health, 60 to 70
million people suffer from of digestive diseases in the U.S. In
2010, 48.3 million ambulatory care visits and 21.7 million
hospitalizations were attributed to digestive ailments. A
2012 study estimated the annual spending on gastrointestinal
diseases in the U.S. at $142 billion, both in direct and
indirect costs.
Disease-Specific Innovation
Many of the ongoing innovation efforts in the field of
gastroenterology focus on specific diseases. The following
paragraphs present an overview of recent advancements.
I. Irritable Bowel Syndrome (IBS)
An estimated 12 percent of
Americans suffer from IBS, a chronic condition that affects the
large intestine (colon). There is currently no specific
diagnostic test for IBS. However, a recent study in the
Netherlands has found that, when measured together, a
combination of 16 different chemicals in the breath can
accurately identify 89.4 percent of IBS patients. This is a
major step towards the development of innovative, noninvasive
tools for diagnosing and monitoring IBS.
In 2015, the U.S. Food and
Drug Administration (FDA) approved two new drugs for IBS
treatment - Viberzi, made by Allergan PLC, and Xifaxan, by
Valeant Pharmaceuticals International Inc. According to Credence
Research, these new products will boost the IBS drugs market,
which is expected to grow at a compound annual growth rate of
13.89 percent between 2016 and 2022, reaching $1,115.06 million
by the end of that period.
Besides medications, the
dietary approach to treating IBS is also expanding. The
University of Michigan, University of Chicago, and Stanford
University have all adopted the so-called “Low Fodmap” diet as
an option for patients. The innovative diet limits the ingestion
of certain kinds of sugars and other food ingredients that are
hard to digest. A study at Baylor College of Medicine in Houston
verified a reduction in abdominal pain for those following the
Low Fodmap diet as compared to those in a traditional American
diet.
Despite the positive
results in patients embracing the new diet, further research is
necessary to assess how the proposed dietary changes affect the
microbe population in the gut. Preliminary studies have pointed
to a possible reduction in the abundance bacteria, which could
lead to long-term health implications.
II. Gastroesophageal Reflux Disease
(GERD)
GERD is a chronic disorder
that affects the muscle between the esophagus and the stomach,
causing heartburn and indigestion. Some cases of GERD are linked
to hiatal hernia, which occurs when an opening in the diaphragm
allows part of the stomach to move up into the chest thus
facilitating reflux.
St. Louis, Missouri-based
startup EndoStim has created an innovative electrical
stimulation therapy for GERD management. Using a minimally
invasive device, which is implanted laparoscopically, the
treatment delivers low-energy neurostimulation to the lower
esophageal sphincter. Recently announced results from a one-year
multicenter trial have confirmed that EndoStim’s therapy can
significantly improve esophageal acid exposure and overall
quality of life in GERD patients that are only partially
responsive to traditional treatments. The treatment was also
found safe and well tolerated.
III. Crohn’s Disease Crohn’s disease
is a chronic condition that causes inflammation of the bowel
tissue, often leading to abdominal pain, severe diarrhea,
fatigue, weight loss, and malnutrition. In some cases, Crohn’s
disease can have life-threatening complications.
A recent study by
researchers at Harvard Medical School revealed that children
with Crohn’s disease have differences in brain structure when
compared to their healthy counterparts. These differences were
found to correlate positively with steroid use and the severity
of inflammation. Gastroenterology & Endoscopy News reported,
in June 2016, that “[when] compared with controls, patients with
Crohn’s disease had thinner cortices in posterior brain regions,
reduced subcortical volume and lower white matter density, as
well as poorer memory and cognition.”
For now, there are still
various unanswered questions regarding how steroid use and
underlying pathways in Crohn’s disease may change the brain on a
cellular and molecular level. Since participants were measured
only once, further studies will be necessary to assess how the
disease might change the brain over time. This important line of
research may help shed light on the psychological dysfunctions
that often affect pediatric patients with Crohn’s disease.
In May 2016,
pharmaceutical company AbbVie announced that a recently licensed
drug candidate was successful in a phase-two trial of Crohn’s
disease. The drug, called risankizumab, is part of a novel group
of biologic products that target interleukins, small proteins
that associate with inflammation. After 12 weeks of treatment,
24 to 37 percent of participants were symptom-free and in
remission, while only 15 percent of those in the placebo group
were in the same conditions. The treated group also presented
fewer adverse events. These results are considered promising,
particularly for patients who have failed to respond to other
treatments.
IV. Ulcerative Colitis (UC)
UC is a type of autoimmune
disease characterized by an over activation of immune cells in
the lining of the gut, which causes inflammation and leads to
chronic, painful bowel movements and long-lasting ulcers in the
digestive tract. Symptoms usually develop over time leading to
debilitating and, in some cases, even life-threatening
complications.
A new study presented at
the Digestive Disease Week 2016 demonstrates that fecal
microbiota transplantation can help patients suffering from UC.
In a multi-centered trial, researchers from the University of
New South Wales, Australia found that 44 percent of patients who
were resistant to conventional UC therapies reported their
symptoms gone after the transplantation. 27 percent had healing
or substantial improvements in their digestive tracts verified
through endoscopic examination.
By recognizing the role of
gut microbiota in health and disease, researchers aim to use the
transplantation as a means to treat the underlying causes of UC,
as opposed to targeting its symptoms, as most of the available
therapies do.
Headquartered in Horsham,
Pennsylvania, Janssen Biotech has recently published a study
according to which monocle antibody Simponi (golimumab), which
has been traditionally recommended for treating moderate to
severe rheumatoid arthritis, active psoriatic arthritis, and
active ankylosing spondylitis, is also effective as therapy for
UC. According to interim results, presented in March 2016,
Simponi induced clinical response in more than two-thirds of
patients participating in the so-called GO-COLITIS trial. This
innovative use of the drug has led to “significant improvements
in generic quality of life (QoL) and disease-specific QoL,
including bowel symptoms, emotional function, systemic symptoms
and social function,” as reported by the participants.
Immunotherapy, an emerging
line of treatment that regulates immune responses, is also a
promising alternative for UC. Researchers at University of
California San Diego School of Medicine have recently
demonstrated that Ozanimod, an experimental immunotherapy drug,
may be effective in treating the condition. The new drug
prevents white blood cells from leaving the lymph nodes and
reaching the gut, where they cause inflammation. Preliminary
results of the ongoing clinical trial have shown that the
innovative treatment can induce remission, reduce rectal
bleeding, and heal the mucosal lining of the intestine. Contrary
to conventional inflammatory bowel disease drugs, Ozanimod does
not suppress the immune system to the point of making patients
more vulnerable to infection or cancer, which is considered a
major advancement.
V. Stomach Cancer
According to the latest
data by the World Health Organization, stomach cancer is the
third leading cause of cancer deaths worldwide. The
American Cancer Society estimates that over 26 thousand new
stomach cancer diagnoses and more than 10 thousand stomach
cancer deaths will occur in 2016 in the U.S.
Recent advancements in
cancer immunotherapy are a source of renewed hope in the face of
such devastating condition. Designed to harness the body’s own
immune system to combat disease, immunotherapy is arguably the
most promising and rapidly evolving alternative for treating
cancer.
In a study presented on
June 5 at the annual meeting of the American Society of Clinical
Oncology, German drug maker Ganymed Pharmaceutical reported the
success of an experimental immunotherapy treatment in helping
increase the life expectancy of stomach cancer patients.
Using an antibody called IMAB362, the therapy trains the immune
system to identify a specific protein found on the surface of
gastric tumors and to recognize them as a threat.
In addition to developing
new treatment options, it is crucial to understand why treatment
responses vary so widely among patients and thus improve the
ability to identify the best approach to each individual case.
In an effort to advance this personalized view of gastric
cancer, researchers at the Institute of Cancer Research in
London recently discovered that the measurements of copies of a
single gene circulating in the bloodstream are good predictors
of a patient’s likelihood to respond to treatment. The FGFR2
gene is a protein that allows for cancerous cells to grow. In a
clinical trial, high levels of FGFR2 correlated with a greater
efficacy of FGFR inhibitor AZ4547.
VI. Colorectal Cancer
Cancers that start in the
colon or rectum are the third most common type of cancer
affecting both men and women in the U.S. According to The
National Institutes of Health there were over 1.17 million
people living with colorectal cancer in the country in 2013.
More than 134 thousand new diagnoses are expected to occur in
2016.
A collaboration between
researchers at the Gibbs Cancer Center & Research Institute
in Spartanburg, South Carolina and the Moffitt Cancer Center in
Tampa, Florida has revealed the prognostic role of Adenomatous
Polyposis Coli (APC) in colorectal cancers. Due to its
tumor-suppressing role, APC has long been referred to as the
“gatekeeper” in the offset of colon cancer. APC mutation is
verified in more than 70 percent of cases.
DNA sequencing from one of
the world’s largest colon cancer database has showed that, in
addition to the participation in the development of cancer, APC
can have a prognostic effect and serve as a predictor of
long-term outcomes. For instance, the study revealed that tumors
with no APC mutation along with those containing two mutated
genes are the ones to produce the worst outcomes. The research
also demonstrated the prognostic capabilities of the locations,
types, and numbers of mutations within the APC gene.
Researchers believe that
APC sequencing can be the basis of a new, personalized approach
to colon cancer, in which medical decisions are tailored to each
patient’s needs. The ongoing collaboration aims to
continue to analyze DNA sequencing from APC and other genes in
an effort to establish new clinical applications, such as the
prediction of drug responses.
Genetic analysis is also
at the basis of a new study at the University of Colorado Cancer
Center. The initiative aims to address the increasing prevalence
of colorectal cancer in patients under 50, which has increased
by 11.4 percent between 2004 and 2013 – in contrast, cases in
patients over 50 decreased by 2.5 percent during the same
period.
According to the study,
the remarkably aggressive nature of young-onset cases may be
explained by alterations in genes involved in the so-called WNT
signaling pathway, which is responsible for driving growth,
survival, and proliferation of cancer stem cells. These
mutations are more frequently found in patients under 50 and can
thus be linked to the aggressiveness of colorectal cancer among
this population. Researchers at the University of Colorado
Cancer Center, who have also been working on clinical trials
testing WNT inhibitors, intend to use these recent findings to
identify the best treatment options for younger patients.
VII. Liver Cancer
Lawrenceville, New
Jersey-based oncology company Celsion Corporation recently
announced a potentially curative treatment for primary liver
cancer. The new therapy is based on Celsion’s proprietary
ThermoDox, a heat-activated encapsulation of cancer drug
doxorubicin. Designed to be used in combination with
hyperthermic treatments, such as radiofrequency thermal ablation
(RFA), microwave hyperthermia, and high- intensity focused
ultrasound (HIFU), ThermoDox is delivered by intravenous
infusion. When exposed to a certain temperature, it changes in
structure and creates openings through which the drug is
delivered directly into the targeted tumor.
In an article published on
June 21, Celsion presented the results of a comprehensive
clinical evaluation according to which ThermoDox, when used in
combination with RFA standardized to a minimum dwell time of 45
minutes, may increase the overall survival (OS) of primary liver
cancer patients. In its latest study, the company verified an
average 58 percent improvement in OS for patients treat with
ThermoDox plus standardized RFA as compared to those exposed to
RFA alone, which translates into a 25.4-month survival benefit.
In order to test and
confirm these results, Celsion has launched the OPTIMA study,
which is expected to involve 550 patients at up to 75 different
locations in North America, Europe, and Asia.
Microbiome Research
The
immense community of microbes residing in and on the human body
is known as the microbiome, or microbiota. The
microbes in our bodies perform crucial tasks, such as 1)
contributing to metabolic functions; 2) protecting against
pathogens; and 3) educating the immune system. Gut bacteria are
interesting examples of the symbiotic, mutually beneficial
relationship between host and microbiome. They are integral to
the digestion process due to their ability to generate nutrients
from materials that would be otherwise indigestible.
Research has shown,
however, that the role of gut microbiome goes far beyond the
digestive processes. In fact, changes in the gut microbiota have
been linked to a wide range of health conditions, including
diabetes, autism, autoimmune diseases, and a variety of
disorders affecting the digestive system, such as irritable
bowel syndrome, inflammatory bowel disease, and Clostridium
difficile infection. Recent findings regarding the role of the
microbiome in human health have opened the way to a fast-paced
race to develop new treatments and diagnostic tools based on
microbes.
Located in Cambridge,
Massachusetts, Seres Therapeutics aims to pioneer the world of
“revolutionary microbiome-based therapeutics.” According to the
MIT Technology Review, Seres has two experimental drugs
currently in clinical trials - one for ulcerative colitis and
the other for Clostridium difficile. Sophisticated genetic
analysis of microbes and human cells in the gut has allowed the
company to identify “keystone organisms” that help restore the
healthy microbiome after disruptions caused by each of the
diseases. These organisms are at the basis of the innovative
medications.
In a recently announced
partnership, Massachusetts General Hospital of the Harvard
Medical School and Seres will work together in the development
of microbiome-based therapeutics for obesity and related
metabolic disorders.
Three-year-old startup
Synlogic is also engaged in creating innovative treatments based
on the microbiome. Also located in Cambridge, Massachusetts, the
company uses bacteria native to the human gut to develop
genetically engineered organisms that, once introduced to the
patient’s body, perform therapeutic functions, such as “removing
unwanted substances the body is retaining as the result of a
metabolic disorder”. The combination of synthetic biology and
microbiome research promises to shed light on groundbreaking new
avenues of treatment for a variety of diseases.
Information Technology
Health information technology can transform the practice of
gastroenterology. Big data analytics, mobile health
applications, and wearable technologies are three particularly
promising areas that can help refine treatments and enhance
patient engagement. Examples of innovative mobile
applications include MyGiHealth, designed by academic teams at
Cedars-Sinai Medical Center, the University of Michigan and the
University of California, Los Angeles. The app uses
evidence-based tools to allow patients to assess, track, and
compare symptoms to benchmarks. It also offers “education
prescriptions”, which are customized educational information
based on each user’s symptoms.
Founded in 2014 and
headquartered in Phoenix, Arizona, Smart Clinic is also an
example of mobile application designed to enhance patient
compliance and to facilitate communication with healthcare
providers. In addition to providing secure messaging between
doctors and patients, Smart Clinic educates patients about their
treatments and remotely sends preparation instructions for a
variety of endoscopic procedures.
When it comes to wearable
technology, biosensors promise to revolutionize patient
monitoring. Cleared by the FDA in 2015, Abstats is a system of
sensors and signal processing analytics invented at UCLA to
provide data-driven, cost-effective insight into the best
protocols for patients recovering from gastrointestinal surgery.
The solution includes a pair of sensors placed on the abdomen,
which continuously detect and analyze the vibrational waves
produced by intestinal muscular motion. The collected data helps
doctors determine the pace of digestive recovery and take
well-informed post-surgical decisions. Prior to the use of
sensors, doctors had to rely on stethoscope or simply on the
patient’s reports of discomfort, which can be remarkably
inaccurate.
Imaging Technology
Technological advancements in gastroenterology also include
innovation in medical devices, particularly imaging technology
that helps detect and monitor a variety of gastrointestinal
disorders. Recent developments include high-definition
white-light endoscopy, which allows for a detailed view of the
colonic mucosa, full-spectrum endoscopy, which provides wider
views of the colon lumen, along with virtual chromoendoscopy
systems that enhance visibility by using specific light
wavelengths.
Based in San Jose,
California, Avantis Medical Systems has been at the forefront of
digital imaging innovation. The company has recently launched
the Third Eye Panoramic, which can be attached to any standard
colonoscope to provide two additional video cameras, generating
a 330 degrees panoramic view.
Conclusion
From
the development of new therapies to the use of advanced
information and imaging technology, innovative efforts can
significantly improve the lives of those suffering from
gastrointestinal disorders. R&D tax credits are available to
help support and stimulate companies engaged in gastroenterology
research.
