Breaking News
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 - 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
February 20, 2018 - Researchers identify fifteen genes that determine our facial features
February 20, 2018 - Morning Break: New Health IT Player; Luxturna No Bargain; Nuclear Freakout
February 20, 2018 - How does it compare? Hospice care at home, at assisted living facility, at nursing home
February 19, 2018 - Scientists develop water-soluble warped nanographene for bioimaging
February 19, 2018 - It’s Not Your Imagination: You’re Hungrier After Losing Weight
February 19, 2018 - Antihypertensive Use At Delivery Rising in Preeclampsia
February 19, 2018 - A centuries-old math equation used to solve a modern-day genetics challenge
February 19, 2018 - Liquid biopsies could be used as new predictive marker for metastatic TNBC
February 19, 2018 - Russian researchers develop new multi-layered biodegradable scaffolds
February 19, 2018 - Are ‘Vaccine Skeptics’ Responsible for Flu Deaths?
February 19, 2018 - Hidden genetic effects behind immune diseases may be missed, study suggests
February 19, 2018 - Emergency nurses experience regular verbal and physical abuse
February 19, 2018 - Study sheds light on biology that guides behavior across different stages of life
February 19, 2018 - Morning Break: Transgender Breast Feeding; Brazilian ‘Pro-Vaxxers’; Post-Stroke Exercise
Experimental molecular therapy restores insulation on peripheral nerves in mice

Experimental molecular therapy restores insulation on peripheral nerves in mice

image_pdfDownload PDFimage_print

When the body attacks its own healthy tissues in an autoimmune disease, peripheral nerve damage handicaps people and causes persistent neuropathic pain when insulation on healing nerves doesn’t fully regenerate.

Unfortunately, there are no effective ways to treat the condition. Now scientists at Cincinnati Children’s Hospital Medical Center describe in Nature Medicine an experimental molecular therapy that restores insulation on peripheral nerves in mice, improves limb function, and results in less observable discomfort.

Published Feb. 12, the study’s principal investigator is Q. Richard Lu, PhD, director of the Cincinnati Children’s Brain Tumor Center

To identify possible therapies, the international team of investigators performed small-molecule epigenetic screening for compounds that inhibit enzymes involved in epigenetic changes on chromosomes. These changes alter how gene activity in cells is regulated. The authors identified small molecular inhibitors already used to treat certain cancers and tested them in experimental treatments on mice with injured sciatic nerves.

The molecular compounds target the enzyme HDAC3 (histone deacetylase 3). Study data show that HDAC3 inhibits regenerating insulation on recovering peripheral nerves.

“Remarkably, temporary inhibition of HDAC3 robustly accelerated the formation of myelin that helps insulate peripheral nerves,” Lu says. “This promoted functional recovery in the animals after peripheral nerve injury.”

Restoring Signal Relays

The peripheral nervous system relays signals from the brain and spinal cord (the central nervous system) to limbs and organs. HDAC3 is an enzyme found in humans and mice. Its usual job in peripheral nerve formation is to act as a molecular brake on the production of the myelin coating by Schwann cells.

After peripheral nerve injury, HDAC3 initiates epigenetic changes to chromosomes and gene regulation that excessively restrict myelin regeneration. This results in nerve insulation that is too thin or not totally formed, blocking or slowing signals between the spinal cord, extremities and organs.

Timing is Crucial

Researchers carefully timed their targeted treatments when inhibiting HDAC3, treating the mouse models of nerve injury only during a critical phase of nerve regeneration. This resulted in the right amount of re-myelination to restore normal function in the animals.

Getting the timing right on transient treatment is critical, Lu says. Researchers show that blocking HDAC3 for too long allows myelin to overgrow and cause excessively thick insulation. This also can lead to functional problems in extremities, according to study data.

From Science to Medicine

Translating data in the current study to clinical application in human patients will require extensive additional research, Lu says. Now that the prospective therapy has been successfully tested in mice, researchers are exploring additional research in animal models that more closely mimic the repair of injured peripheral nerves in people. This includes looking specifically at some demyelinating diseases that affect the central nervous system, such as multiple sclerosis.

Lu said this work will allow scientists to replicate and verify their findings in mice and other laboratory models. They also will be able to test possible dosing levels. If results are positive, Lu said researchers could pursue possible Phase I clinical trials in patients having deficient myelin in their peripheral and central nervous systems.

Source:

https://www.cincinnatichildrens.org/news/release/2018/restoring-nerve-insulation

Tagged with:

About author

Related Articles