Rare and Orphan Diseases at Target Health Inc.

 

One of Target Health’s expertise is in the area of rare and orphan diseases. Our expertise is not just in obtaining Orphan Drug Designations in multiple areas, but also the regulatory strategy to optimize the path to the market. For one program, we worked with our client to propose to FDA to go directly from Phase 1 in normal volunteers to a pivotal trial with 30 patients with just 2 doses of the drug and no placebo arm. The drug was approved and the company saved at least 2 years by not having to do a phase 2 study. In additional, the NDA was a rolling submission, so that when the last patient visit occurred in September, the final NDA was submitted in December, just 3 months later. Of course, the planning of the submission started a year in advance which made for a smooth transition. A recent Orphan Drug Designation was approved for a rare epilepsy in children and a Fast Track Designation cleared for a metabolic disease.

 

For more information about Target Health contact Warren Pearlson (212-681-2100 ext. 165). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel. The Target Health software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website.

 

Joyce Hays, Founder and Editor in Chief of On Target

Jules Mitchel, Editor

 

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Cell Signaling

Notch-mediated juxtacrine signal between adjacent cells.

 

Graphic credit: Fred the Oysteri. The source code of this SVG is valid. This vector graphics image was created with Adobe Illustrator. – Graphic: National Institute of Health. U.S. http://ccr.cancer.gov/staff/images/1372_Fortini_178.gif, Public Domain, https://commons.wikimedia.org/w/index.php?curid=36238400

 

In 1999 Dr. Gunter Blobel of the Rockefeller University in New York received the Nobel Laureate in Medicine or Physiology for his discovery of this protein signal system of “ZIP codes.“

 

ZIP code, protein is an informal name for a molecular cell biology system of signals or “address tags“ that guide the movement of a protein within a cell. In more technical terms, protein ZIP codes** are molecular signals that direct the 1) ___ from the endoplasmic reticulum, where it is assembled, to the cytoplasm of the cell and into other cellular compartments such as the nucleus of the cell. Mutations in this molecular system of protein “ZIP codes“ have been found to cause several human genetic (hereditary) disorders, including cystic fibrosis and hyperoxaluria (a disorder that causes a special type of stone to form in the urine beginning in childhood). It is well-known that the body’s immune response depends on proper direction of cells through the bloodstream and into the tissues that need them. But exactly how this cell trafficking occurred was unknown. Studies have shown that just as ZIP codes direct mail to particular communities, special molecules that sit on cell surfaces guide the cells through the bloodstream to their tissue destinations. However, before it can slip into the target tissue, a cell exiting the bloodstream must first adhere to the vessel wall. Blood cells contain more than 100 adhesion molecules, yet only a handful of these form bonds that can admit the cell into the surrounding tissue. These so-called Goldilocks molecules possess very specific chemical and mechanical properties that enable the formation of bonds of a particular strength and duration. Adhesion cannot be too tight, or the cells will bind to the vessel 2) ___ and never let go. It also can’t be too weak, or the blood cell will just pass on by. To study this phenomenon, computer simulations we used to explore the adhesion between a blood-borne cell and a surface akin to a vessel wall. Interestingly, this technique could one day be used to design 3) ___ with tailored mechanical properties.

 

Cell signaling is part of any communication process that governs basic activities of cells and coordinates all cell actions. The ability of cells to perceive and correctly respond to their microenvironment is the basis of development, tissue repair, and immunity, as well as normal tissue homeostasis. Errors in signaling interactions and cellular information processing are responsible for diseases such as cancer, autoimmunity, and diabetes. By understanding cell 4) ___, diseases may be treated more effectively and, theoretically, artificial tissues may be created. Traditional work in biology has focused on studying individual parts of cell signaling pathways. Systems biology research helps us to understand the underlying structure of cell signaling networks and how changes in these networks may affect the transmission and flow of information (signal transduction). Such 5) ___ are complex systems in their organization and may exhibit a number of emergent properties including bi-stability and ultrasensitivity. Cell signaling has been most extensively studied in the context of human diseases and signaling between cells of a single organism. However, cell signaling may also occur between the cells of two different organisms. In many mammals, early embryo cells exchange signals with cells of the uterus. In the human gastrointestinal tract, bacteria exchange signals with each other and with human epithelial and immune system cells.

 

During mating of the yeast Saccharomyces cerevisiae, some cells send a peptide signal (mating factor pheromones) into their environment. The mating factor peptide may bind to a cell surface receptor on other 6)___ cells and induce them to prepare for mating. Cell signaling can be classified to be mechanical and biochemical based on the type of the signal. Mechanical signals are the forces exerted on the cell and the forces produced by the cell. These forces can both be sensed and responded by the cells. Biochemical signals are the biochemical molecules such as proteins, lipids, ions and gases. These signals can be categorized based on the distance between signaling and responder cells. Signaling within, between, and among cells is subdivided into the following classifications:

 

Intracrine signals are produced by the target cell that stay within the target cell.

Autocrine signals are produced by the target cell, are secreted, and affect the target cell itself via receptors. Sometimes autocrine cells can target cells close by if they are the same type of cell as the emitting cell. An example of this are immune cells.

Juxtacrine signals target adjacent (touching) cells. These signals are transmitted along cell membranes via protein or lipid components integral to the membrane and are capable of affecting either the emitting cell or cells immediately adjacent.

Paracrine signals target cells in the vicinity of the emitting cell. Neurotransmitters represent an example.

Endocrine signals target distant cells. Endocrine cells produce hormones that travel through the blood to reach all parts of the body.

 

Cells communicate with each other via direct contact (juxtacrine signaling), over short distances (paracrine signaling), or over large distances and/or scales (endocrine signaling). Some cell-cell communication requires direct cell-cell contact. Some cells can form gap junctions that connect their cytoplasm to the cytoplasm of adjacent cells. In cardiac muscle, gap junctions between adjacent cells allows for action potential propagation from the cardiac pacemaker region of the heart to spread and coordinately cause contraction of the 7) ___. The notch signaling mechanism is an example of juxtacrine signaling (also known as contact-dependent signaling) in which two adjacent cells must make physical contact in order to communicate. This requirement for direct contact allows for very precise control of cell differentiation during embryonic development.

 

In the worm Caenorhabditis elegans, two cells of the developing gonad each have an equal chance of terminally differentiating or becoming a uterine precursor cell that continues to divide. The choice of which cell continues to divide is controlled by competition of cell surface signals. One cell will happen to produce more of a cell surface protein that activates the Notch receptor on the adjacent cell. This activates a feedback loop or system that reduces Notch expression in the cell that will differentiate and that increases Notch on the surface of the cell that continues as a stem cell.

 

Hormones are produced by endocrine cells and they travel through the blood to reach all parts of the body. Specificity of signaling can be controlled if only some cells can respond to a particular hormone. Paracrine signals such as retinoic acid target only cells in the vicinity of the emitting cell. Neurotransmitters represent another example of a paracrine signal. Some signaling molecules can function as both a hormone and a neurotransmitter. For example, epinephrine and norepinephrine can function as hormones when released from the adrenal gland and are transported to the heart by way of the blood stream. Norepinephrine can also be produced by neurons to function as a neurotransmitter within the brain. Estrogen can be released by the ovary and function as a 8) ___ or act locally via paracrine or autocrine signaling. Active species of oxygen and nitric oxide can also act as cellular messengers. This process is dubbed redox signaling.

 

In a multicellular organism, signaling between cells occurs either through release into the extracellular space, divided in paracrine signaling (over short distances) and endocrine signaling (over long distances), or by direct contact, known as juxtacrine signaling. Autocrine signaling is a special case of paracrine signaling where the secreting cell has the ability to respond to the secreted signaling molecule. Synaptic signaling is a special case of paracrine signaling (for chemical synapses) or juxtacrine signaling (for electrical synapses) between neurons and target cells. Signaling molecules interact with a target cell as a ligand to cell surface receptors, and/or by entering into the cell through its membrane or endocytosis for intracrine signaling. This generally results in the activation of second messengers, leading to various physiological effects. Neurotransmitters are signaling molecules of the nervous system, also including neuropeptides and neuromodulators. Neurotransmitters like the catecholamines are also secreted by the endocrine system into the systemic circulation. Cytokines are signaling molecules of the immune system, with a primary paracrine or juxtacrine role, though they can during significant immune responses have a strong presence in the circulation, with systemic effect (altering iron metabolism or body temperature). Growth factors can be considered as cytokines or a different class.

 

Signaling molecules can belong to several chemical classes: lipids, phospholipids, amino acids, monoamines, proteins, glycoproteins, or gases. Signaling molecules binding surface receptors are generally large and hydrophilic (e.g. TRH, vasopressin, acetylcholine), while those entering the cell are generally small and hydrophobic (e.g. glucocorticoids, thyroid hormones, cholecalciferol, retinoic acid), but important exceptions to both are numerous, and a same molecule can act both via surface receptor or in an intracrine manner to different effects. In intracrine signaling, once inside the 9) ___, a signaling molecule can bind to intracellular receptors, other elements, or stimulate enzyme activity (e.g. gasses). Hydrogen sulfide is produced in small amounts by some cells of the human body and has a number of biological signaling functions. Only two other such gases are currently known to act as signaling molecules in the human body: nitric oxide and carbon monoxide.

 

Cells receive information from their neighbors through a class of proteins known as receptors. Notch is a cell surface protein that functions as a 10) ___. Animals have a small set of genes that code for signaling proteins that interact specifically with Notch receptors and stimulate a response in cells that express Notch on their surface. Molecules that activate (or, in some cases, inhibit) receptors can be classified as hormones, neurotransmitters, cytokines, and growth factors, in general called receptor ligands. Ligand receptor interactions such as that of the Notch receptor interaction, are known to be the main interactions responsible for cell signaling mechanisms and communication.

 

** For the benefit of readers, not familiar with the United States mail system, the term “ZIP code“ refers to address codes of the U.S. Postal Service used to sort mail into geographic regions.

Sources: Scientific American; Wikipedia

 

ANSWERS: 1) protein; 2) wall; 3) bonds; 4) signaling; 5) networks; 6) yeast; 7) heart; 8) hormone; 9) cell; 10) receptor

 

Gunter Blobel MD, PhD (1936 – 2018) Redefined Cell Biology

Gunter Blobel: Died a few days ago, on 18 February 2018 (aged 81): From Wikimedia Commons, the free media repository

 

Gunter Blobel (May 21, 1936 – February 18, 2018 was a Silesian German and American biologist and 1999 Nobel Prize laureate in Physiology for the discovery that proteins have intrinsic signals that govern their transport and localization in the cell. Blobel was born in Waltersdorf in the Prussian Province of Lower Silesia, now a part of Poland. In January 1945 his family fled from native Silesia from the advancing Red Army. After the war Blobel grew up and attended gymnasium in the Saxon town of Freiberg. He graduated at the University of Tubingen in 1960 with MD and received his Ph.D. from the University of Wisconsin-Madison in 1967. Blobel joined the Rockefeller University faculty 51 years ago where he was the John D. Rockefeller Jr. Professor. He was also a Howard Hughes Medical Institute Investigator since 1986.

 

Blobel was awarded the 1999 Nobel Prize in Physiology or Medicine for the discovery of signal peptides. Signal peptides form an integral part of protein targeting, a mechanism for cells to direct newly synthesized protein molecules to their proper location by means of an “address tag“ (i.e. a signal peptide) within the molecule. Proteins that are manufactured within cells must be transported to the sites where they are needed. Blobel discovered a system of intrinsic signals that explain how cells are able to accurately distribute billions of such proteins within a cell each day. Along with his colleagues, Blobel learned that sequences in proteins were responsible for directing traffic, matching up these “zip codes“ with transport machinery in the cell that facilitate targeting to the proper cellular membranes. This connection results in the proteins either passing through the membranes or becoming embedded within them. His observations were central to uniting the fields of molecular biology, which deals primarily with proteins and nucleic acids, and cell biology, which is focused on the structures inside cells, called organelles. In addition, he found that the same system plays a role across all eukaryotes, ranging from yeast to humans.

 

Blobel became well known for his direct and active support for the rebuilding of Dresden in Germany, becoming, in 1994, the founder and president of the nonprofit “Friends of Dresden, Inc.“ He donated all of the Nobel award money to the restoration of Dresden, in particular for the rebuilding of the Frauenkirche (completed in 2005) and the building of a new synagogue. In Leipzig he pursued a rebuilding of the Paulinerkirche, the university church of the University of Leipzig, which had been blown up by the communist regime of East Germany in 1968, arguing “this is a shrine of German cultural history, connected to the most important names in German cultural history.“ In addition to his research at the Rockefeller University in New York City from 1968 to 2018, Blobel lived in Manhattan’s Upper East Side with his wife, Laura Maioglio (owner of Barbetta Restaurant in Manhattan). He was on the board of directors for Nestle and the Board of Scientific Governors at The Scripps Research Institute. Furthermore, he was Co-Founder and Chairman of the Scientific Advisory Board for Chromocell Corporation. He sat on the Selection Committee for Life Science and Medicine which chooses winners of the Shaw Prize.

 

Excellent video about the work of Dr. Gunter Blobel

 

Hospitals Testing Therapies to Prevent 2 Common Bacterial Infections

 

The World Health Organization recently included P. aeruginosa and S. aureus on a list of antibiotic-resistant bacteria that pose the greatest risk to human health. People in healthcare settings with weakened immune systems, especially those on breathing machines or with catheters, face an increased risk of becoming seriously ill from these infections. The Centers for Disease Control and Prevention has also clearly indicated that Staphylococcus bacteria are a leading cause of healthcare-associated infections, such as pneumonia, bacteremia, and heart valve and bone infections. In 2011, methicillin-resistant S. aureus (MRSA) caused more than 80,000 serious infections and 11,285 related deaths in the United States, according to the CDC. P. aeruginosa can cause bloodstream infections and pneumonia that can be fatal. Approximately 51,000 healthcare-associated P. aeruginosa infections occur each year in the United States, and about 6,700 of these are drug-resistant, leading to more than 400 deaths annually, according to CDC estimates based on a 2011 survey.

 

The mission of the Antibacterial Resistance Leadership Group (ARLG), is to prioritize, design and execute clinical research that will reduce the public health threat of antibacterial resistance. The ALRG has combined with a large international consortium of international trials supported by MedImmune, the global biologics research and development arm of AstraZeneca, and the Brussels-based Innovative Medicines Initiative Joint Undertaking and the Combatting Antimicrobial Resistance in Europe (COMBACTE) consortium, to enroll 30 adult patients from 15 intensive care units in the US.

 

One trial, called EVADE, is evaluating the safety of the investigational medicine MEDI3902 (developed by MedImmune) and its ability to prevent pneumonia caused by Pseudomonas aeruginosa. The other trial, called SAATELLITE, is testing the safety of another investigational MedImmune medicine, suvratoxumab (previously known as MEDI4893), and its ability to prevent disease caused by Staphylococcus aureus. Both trials are randomized, placebo-controlled, and double-blind, meaning neither the participants nor the investigators will know who receives a placebo.

 

MEDI3902 and suvratoxumab are both monoclonal antibodies being investigated as preventive therapies. The medicines are not antibiotics but can be administered alongside standard antibiotic therapy. Monoclonal antibodies have been developed for use against diseases such as cancer, Ebola and respiratory syncytial virus, but rarely have been used to target bacterial pathogens.

 

All participants in both the EVADE and SAATELLITE trials will be on mechanical ventilation in the intensive care unit at the time of enrollment. Trial investigators will provide information about the purpose and possible risks and benefits of the study so that patients can ask questions before they agree to participate. If a patient is unconscious or otherwise unable to consent during the screening process, a legally authorized representative can provide initial consent. Participants in the EVADE trial must be colonized with P. aeruginosa bacteria in the lower respiratory tract but display no signs of pneumonia. They will be randomly assigned to receive either one intravenous (IV) infusion of MEDI3902 or placebo. Investigators will check for incident pneumonia caused by P. aeruginosa for 21 days, and will monitor participants for 49 days total. Similarly, participants in the SAATELLITE trial must be colonized with S. aureus in the lower respiratory tract but free of S. aureus-related disease. They will be randomly assigned to receive either one IV infusion of suvratoxumab or a placebo. Investigators will evaluate the incidence of S. aureus-related pneumonia for 30 days, and monitor participants for 190 days total. Participants in both the EVADE and SAATELLITE trials will be regularly evaluated for any treatment-related safety issues.

 

Graduates of Early Childhood Program Show Greater Educational Gains in Adulthood

 

The Child-Parent Centers (CPC) program in Chicago, IL, provides intensive instruction in reading and math, combined with frequent educational field trips, from pre-kindergarten through third grade. The program also provides parents with job and parenting skills training, educational classes and social services. In addition, the program encouraged parents to volunteer in classrooms, assist with field trips and participate in parenting support groups.

 

According to an article published online in JAMA Pediatrics (29 January 2018), students who participated CPC program from preschool to third grade were more likely to achieve an academic degree beyond high school, compared to a similar group that received other intervention services as children. The study followed the 30-year progress of 989 children who attended the CPC program in inner-city Chicago as preschoolers. The study compared the educational outcomes of graduates from 20 CPC schools to those of 550 children from low-income families who attended 5 other early randomly selected schools in the Chicago area with childhood intervention programs. The study collected information on the children from administrative records, schools and families, from birth through 35 years of age.

 

Results showed that on average, graduates of the CPC program — whether they took part in preschool only or attended until second or third grade — completed more years of education than those who participated in other early intervention programs. Among those receiving an intervention in preschool, children in the CPC group were more likely as adults to achieve an associate’s degree or higher (15.7% vs. 10.7%), including a bachelor’s degree (11% vs. 7.8%) and master’s degree (4.2% vs. 1.5%). CPC graduates who attended the program through second or third grade had even higher educational gains than their counterparts: associate’s degree or higher (18.5% vs. 12.5%), including a bachelor’s degree (14.3% vs. 8.2%) and master’s degree (5.9% vs. 2.3%).

 

According to the authors, their study is the first to follow participants past age 25, a time in life when many people attain advanced degrees. Their previous research has shown that CPC graduates have gone on to have higher incomes, lower rates of serious crime and incarceration and lower rates of depression, compared to those who participated in other early interventions. The authors added that successful early childhood programs can also improve adult health. They noted that adults with less education are more likely to adopt unhealthy habits like smoking and to experience high blood pressure, obesity and mental health problems.

 

FDA Clears First Blood Test to Aid in the Evaluation of Concussion in Adults

 

According to the U.S. Centers for Disease Control and Prevention, in 2013 there were approximately 2.8 million TBI-related emergency department visits, hospitalizations and deaths in the U.S. Of these cases, TBI contributed to the deaths of nearly 50,000 people. TBI is caused by a bump, blow or jolt to the head or a penetrating head injury that disrupts the brain’s normal functioning. Its severity may range from mild to severe, with 75% of TBIs that occur each year being assessed as mTBIs or concussions. A majority of patients with concussion symptoms have a negative CT scan. Potential effects of TBI can include impaired thinking or memory, movement, sensation or emotional functioning. Most patients with a suspected head injury are examined using a neurological scale, called the 15-point Glasgow Coma Scale, followed by a computed tomography or CT scan of the head to detect brain tissue damage, or intracranial lesions that may require treatment. However, a majority of patients evaluated for mTBI/concussion do not have detectable intracranial lesions after having a CT scan. Availability of a blood test for concussion would help health care professionals determine the need for a CT scan in patients suspected of having mTBI and help prevent unnecessary neuroimaging and associated radiation exposure to patients.

 

The FDA has cleared for marketing the first blood test in adults to evaluate mild traumatic brain injury (mTBI), commonly referred to as concussions. The FDA reviewed and authorized for marketing the Banyan Brain Trauma Indicator in fewer than 6 months as part of its Breakthrough Devices Program. The Brain Trauma Indicator works by measuring levels of proteins, known as UCH-L1 and GFAP, that are released from the brain into blood and measured within 12 hours of head injury. Levels of these blood proteins after mTBI/concussion can help predict which patients may have intracranial lesions visible by CT scan and which won’t. Being able to predict if patients have a low probability of intracranial lesions can help health care professionals in their management of patients and the decision to perform a CT scan. Test results can be available within 3 to 4 hours.

 

The FDA evaluated data from a multi-center, prospective clinical study of 1,947 individual blood samples from adults with suspected mTBI/concussion and reviewed the product’s performance by comparing mTBI/concussion blood tests results with CT scan results. The Brain Trauma Indicator was able to predict the presence of intracranial lesions on a CT scan 97.5% of the time and those who did not have intracranial lesions on a CT scan 99.6% of the time. These findings indicate that the test can reliably predict the absence of intracranial lesions and that health care professionals can incorporate this tool into the standard of care for patients to rule out the need for a CT scan in at least one-third of patients who are suspected of having mTBI.

 

The Brain Trauma Indicator was reviewed under the FDA’s De Novo premarket review pathway, a regulatory pathway for some low- to moderate-risk devices that are novel and for which there is no prior legally marketed device.

 

The FDA is permitting marketing of the Brain Trauma Indicator to Banyan Biomarkers.

Veggies with Chicken & Brown Rice Mixed with Golden Raisins, Pine Nuts and Peanut Sauce

Just Out of the Oven ©Joyce Hays, Target Health Inc. 

 

Peanut sauce is a favorite thing to eat, with green vegetables, like broccoli, spinach and edamame, and it’s this particular peanut sauce that really makes this recipe different and delicious. Adding left-over chicken or turkey to this casserole, makes for a delicious one dish meal. However, if you want a strictly vegan recipe, a few substitutions can easily make it vegan. I’ve tried baking cubes of firm tofu brushed with olive oil, and using them instead of poultry, with good results. You can substitute chicken stock with vegetable broth.

 

Get all of your ingredients lined up on the counter. This kind of organization makes cooking much easier.

 

Lining up the ingredients ©Joyce Hays, Target Health Inc.

 

Ingredients for Peanut Sauce 

1/4 cup natural peanut butter (creamy variety)
2 Tbsp tamari soy sauce (use low-sodium variety)
3 garlic cloves, minced
1/8 tsp grated ginger root (optional)
1/3 cup warm chicken stock or broth

 

Ingredients for the Rest of the Dish

TOFU or POULTRY – One block of the firmest tofu, cut in cubes, stirred in baking dish with extra virgin olive oil and 2 garlic cloves, juiced — bake in 350 degree oven for 20 minutes or stir fry until golden brown. Set aside

 

BROWN RICE – Make the (organic) brown rice and set aside. To enhance the flavor of the rice, boil it in chicken stock instead of water. You can use saffron rice instead if you prefer.

 

BROCCOLI – Clean. Steam or stir fry in olive oil and 1-2 juiced garlic cloves, for 2-3 minutes. Break apart the florets to the size you want. Cut stems into small pieces and use. If you would rather serve the broccoli separately, and not in this casserole, go ahead.

 

14 oz frozen bag (thawed) of organic sodium-free edamame.

1 bunch fresh broccoli

1 cup golden raisins

1 cup pine nuts, toasted ahead of time. You could substitute cashews or peanuts.

2 Tablespoons extra virgin olive oil

2/3 cup cilantro, chopped

1 onion, chopped

3 garlic cloves, chopped

Pinch black pepper (grind to your taste)

Pinch cayenne powder (optional and to your taste)

1 teaspoon turmeric

1 teaspoon cardamom

1/4 teaspoon fresh ginger root, grated (or to your taste)

 

Directions

1. Make the Peanut sauce and set aside

2. Bake or stir-fry the tofu or chicken and set aside

3. Make organic brown rice and set aside. You could also use saffron rice.

 

Here I am sauteing ©Joyce Hays, Target Health Inc.

 

In fry pan, saute the onion and garlic in the olive oil, when onion is transparent, add the cilantro, Pinch black pepper, Pinch cayenne, turmeric, cardamom and grated ginger root, stir well and cook for a few more minutes. Add the thawed out edamame and stir well again. If you need more liquid, gradually add more chicken stock or vegetable broth, and stir.

 

In a large baking dish add the chicken or tofu, brown rice, onion/edamame mixture and stir well. Add all of the broccoli and stir again. Now, add the golden raisins and toasted pine nuts. Finally, pour all of the peanut sauce over all and stir it in well. Use a spatula to get every last bit of this delicious sauce.

 

Bake in 350 oven for 15 to 20 minutes. I raised the heat for the last 5 minutes for a more crispy top. Serve adding some of the cilantro on top for garnish

 

Mixing the Ingredients ©Joyce Hays, Target Health Inc.

 

About to sit down with a nice Cabernet. The veggie casserole with peanut sauce was a great success. We both loved it and came back for more. The edamame is a particularly good addition in this recipe. There was enough left over to be able to enjoy this meal again during the week. ©Joyce Hays, Target Health Inc.

 

Second helping, it was so good ©Joyce Hays, Target Health Inc.

 

 

Have a great week everyone!

From Our Table to Yours

Bon Appetit!