Breaking News
February 21, 2018 - Postnatal depression impacts mother-child relationships for longer time frame
February 21, 2018 - Study describes new protection mechanisms to fight neurodegeneration in Parkinson’s and Alzheimer’s
February 21, 2018 - Tiny ‘brains on chips’ reveal mechanisms underlying brain’s wrinkling process
February 21, 2018 - Bedfont Scientific makes FDA 510(k) submission for clearance of ToxCO monitor
February 21, 2018 - ‘Grey’s Anatomy’ Traumas Lack Realism
February 21, 2018 - Sleep quality improves with help of incontinence drug
February 21, 2018 - Scientists uncover genetic cause behind typhoid’s antibiotic resistance
February 21, 2018 - Study reveals a significant link between heavy alcohol use and dementia
February 21, 2018 - French scientists develop new wearable laser that eradicates skin conditions
February 21, 2018 - People with major depressive disorder have reduced arginine levels, study shows
February 21, 2018 - National Health Spending at $3.5 Trillion in 2017, CMS Says
February 21, 2018 - Substantial inequalities in cesarean births persist in many countries
February 21, 2018 - Early childhood immune signature predicts risk of developing asthma later on
February 21, 2018 - Stanford researchers explore how gut bacteria respond to common changes in habitat
February 21, 2018 - Household Products May Pollute the Air as Much as Your Car Does: Study
February 21, 2018 - Combo Bests Targeted Agent in mRCC
February 21, 2018 - Researchers discover brain pathway that dissociates opioid addiction from analgesia
February 21, 2018 - Scientists uncover how newly discovered gene helps grow blood vessels
February 21, 2018 - Brain’s quality control process holds clues to obesity’s roots
February 21, 2018 - Researchers to study whether menstrual cups can help prevent vaginal infections
February 21, 2018 - MS patients who feel stigmatized more likely to suffer from depression
February 21, 2018 - Vitamin D supplementation during pregnancy could protect against childhood obesity
February 21, 2018 - Lower-Quality Medical Tx Might Have Skewed Key PCI vs CABG Trials
February 21, 2018 - Love and fear are visible across the brain instead of being restricted to any brain region
February 21, 2018 - Researchers discover potential new antimalarial treatment targets
February 21, 2018 - Adults with congenital heart disease have increased risk for dementia, study finds
February 21, 2018 - Clinical trial studying type 1 diabetes reaches full enrollment
February 21, 2018 - Father’s stress affects the brain development of offspring, mice study shows
February 21, 2018 - ESRD Death Declines in Vasculitis Patients
February 21, 2018 - Taking ibuprofen for long periods found to alter human testicular physiology
February 21, 2018 - Google AI device could predict a person’s risk of a heart attack
February 20, 2018 - FDA Approves Domestic Source for Tc-99m Isotopes
February 20, 2018 - Sanofi rejects refund demand faces Philippine suit over dengue vaccine (Update)
February 20, 2018 - Researchers discover that activation of specific enzyme may help suppress tumor metastasis
February 20, 2018 - Blood or marrow transplantation survivors have higher risk of cognitive impairment
February 20, 2018 - Booze Beats Pot at Being Unhealthy: Oregon Poll
February 20, 2018 - Morning Break: ’20 Years Late’; Drugs in the Dirt; Catching Flu in the Dorm
February 20, 2018 - Another piece to the puzzle in naked mole rats’ long, cancer-free life
February 20, 2018 - Scientists identify four viruses that can produce insulin-like hormones
February 20, 2018 - New e-Health solution developed to prevent cardiovascular disease, dementia in senior citizens
February 20, 2018 - New genetic risk score could help guide screening decisions for prostate cancer
February 20, 2018 - Study finds higher risk of stroke among blacks with atrial fibrillation than whites
February 20, 2018 - Physical activity could be used as strategy for diabetes prevention
February 20, 2018 - Researchers develop sensing method for early detection of cancer and diabetes
February 20, 2018 - New wearable electronics could be game-changer for stroke rehabilitation
February 20, 2018 - Immune history influences person’s response to flu vaccine
February 20, 2018 - Research findings could help develop new drugs to prevent, treat dry eye disease
February 20, 2018 - Serenity Now! Learn to Have Patience with Patients
February 20, 2018 - Computer simulation addresses the problem of blood clotting
February 20, 2018 - Women with type 1 diabetes not protected against coronary artery disease
February 20, 2018 - Persistent bloating can be a sign of ovarian cancer, warns charity
February 20, 2018 - Trump administration proposes rule to loosen curbs on short-term health plans
February 20, 2018 - Key protein involved in epigenetic regulation of gene expression guides skin cell renewal
February 20, 2018 - Heart attack symptoms often missed in women
February 20, 2018 - Diagnosis of celiac disease takes 3.5 years for patients who do not report GI symptoms
February 20, 2018 - Study reveals functional dynamics of ion channels
February 20, 2018 - Study explores link between mortality risk and combustible tobacco use
February 20, 2018 - ‘She Trusted Me, and I’d Turned Her Away’
February 20, 2018 - AbbVie and Voyager Therapeutics collaborate to develop new treatments for tauopathies
February 20, 2018 - Fast food makes the immune system more aggressive in the long term
February 20, 2018 - Therapeutic target for glaucoma could have treatment ramifications for Alzheimer’s and Parkinson’s
February 20, 2018 - Overcoming Negative Reviews | Medpage Today
February 20, 2018 - MyD88—villain of allergies and asthma
February 20, 2018 - Food scientists develop rapid screening technique to detect pesticide residue in vegetables
February 20, 2018 - Lab-grown cerebellar cells may help explain how ASD develops at molecular level
February 20, 2018 - Scientists explore connection between bad sleep habits and stiff blood vessels
February 20, 2018 - New Treatment Apalutamide (Erleada) Approved for Prostate Cancer That Resists Hormone Therapy
February 20, 2018 - Do You Really Need My Signature on That?
February 20, 2018 - HIV-1 genetic diversity is higher in vaginal tract than in blood during early infection
February 20, 2018 - Diabetes does not increase work-loss years due to early retirement
February 20, 2018 - Researchers aim to find out how PTSD affects decisions of police
February 20, 2018 - UH Cleveland Medical Center explores novel treatments for uterine fibroids
February 20, 2018 - Flu Vax Efficacy 25% Against Predominant H3N2 Strain So Far
February 20, 2018 - HIV screening most optimal at 25 years of age if no risk factors
February 20, 2018 - Loyola Medicine primary care physician offers advice to minimize risk of flu
February 20, 2018 - Safe sleep recommendations for parents that may help reduce child’s risk of SUID
February 20, 2018 - Why Do So Few Docs Have Buprenorphine Waivers?
February 20, 2018 - Low levels of alcohol good for the brain
February 20, 2018 - Experimental treatment improves invisible symptoms of a man with spinal cord injury
February 20, 2018 - Myriad’s EndoPredict offers better prediction of breast cancer recurrence, analysis shows
Moffitt study identifies new drug target that may reduce GVHD risk

Moffitt study identifies new drug target that may reduce GVHD risk

image_pdfDownload PDFimage_print

Stem cell transplants can cure patients with high-risk leukemia or lymphoma. Graft-versus-host disease (GVHD) is a potentially life-threatening side effect that occurs when the donor’s immune cells attack the recipient’s normal tissues. Moffitt Cancer Center researchers are trying to identify new drug targets to reduce the risk of GVHD. Their new study, published last week in the Proceedings of the National Academy of Sciences, shows a drug that targets the protein JAK2 may reduce the risk of GVHD.

The goal of stem cell transplants is to replenish the bone marrow and eliminate residual cancer using the donor’s immune cells. However, in some cases the donor’s white blood cells mount an immune response against the recipient’s normal tissues. It is estimated that GVHD affects up to half of all stem cell recipients. The symptoms of GVHD can vary from mild to severe and include skin inflammation and rash, liver inflammation, jaundice, gastrointestinal problems, pain, and fatigue. Despite modern immune suppressive medications, death is possible when severe GVHD occurs.

The goal of GVHD treatment is to block the donor immune cells from targeting the body’s normal cells, while at the same time maintaining the ability of the donor cells to target cancer cells for destruction. GVHD is commonly treated with drugs that suppress the immune system, such as glucocorticoids, but the scientific community is trying to find better alternatives with less side effects.

“An effort to identify selective immune suppression whereby GVHD is reduced and the antitumor activity of the graft is preserved is key to improving the success of blood and marrow transplantation,” said Brian C. Betts, M.D, lead study author and associate member of the Blood and Marrow Transplant and Cellular Immunotherapy Department at Moffitt.

The protein JAK2 is believed to be involved in the development of GVHD. In collaboration with researchers from the Medical University of South Carolina, the Moffitt research team wanted to confirm the link and assess if blocking JAK2 could reduce the occurrence of GVHD. They performed experiments with mice that were genetically engineered to be missing the JAK2 gene. They discovered that JAK2 regulates several of the immune cell mechanisms that lead to GVHD. They also showed that donor cells missing the JAK2 gene induced GVHD less than normal donor cells, and the genetically modified cells were still able to target tumor cells for destruction.

These observations suggest drugs that target JAK2 may prevent GVHD and still allow the donor cells to target cancer cells. The researchers confirmed this by transplanting normal stem cells into recipient mice and treating the mice with the drug pacritinib that inhibits JAK2. They discovered that pacritinib reduced the number of immune cells responsible for GVHD and the number of mice that died from GVHD. Importantly, pacritinib did not inhibit the ability of the transplanted stem cells from targeting cancer cells for destruction. The Moffitt research team also discovered that pacritinib could protect mice from tissue graft rejection, suggesting this approach could be used to prevent kidney or liver transplant rejection.

These results suggest that pacritinib may be a potential drug option to prevent GVHD in stem cell recipients. Betts and his Moffitt colleague, Joseph Pidala, M.D., Ph.D., are investigating a phase 1/2 acute GVHD prevention trial combining pacritinib with standard immune suppression after stem cell transplant.

Source:

https://www.moffitt.org/newsroom/press-release-archive/2018/moffitt-researchers-identify-new-target-to-reduce-risk-of-graft-versus-host-disease/

Tagged with:

About author

Related Articles