Breaking News
December 16, 2017 - Research uncovers mechanism implicated in defective function of tumor-associated dendritic cells
December 16, 2017 - OncoBreak: Stubborn Racial Disparities; Paid Medical Leave & Chemo; DIY Gene Tests
December 16, 2017 - Critical link between obesity and diabetes has been identified
December 16, 2017 - Transfusion dependence reduces access to high-quality end-of-life care for leukemia patients
December 16, 2017 - Porvair and Suzhou Tianlong Bio to develop epigenetic analysis technologies
December 16, 2017 - FDA Approves Ixifi (infliximab-qbtx), a Biosimilar to Remicade
December 16, 2017 - Morning Break: Trump to Get Check-Up; Cancerous Transplant; Death Knell for MIPS?
December 16, 2017 - First transcatheter implant for diastolic heart failure successful
December 16, 2017 - ‘Sushi-like’ nanodiscs provide structural snapshots of misfolding proteins
December 16, 2017 - Inherited gene variation may be to blame for poor survival of patients with early-onset breast cancer
December 16, 2017 - Sign-up deadline is Friday, but some people may get extra time
December 16, 2017 - Higher Booze Taxes Might Pay Off for Public Health
December 16, 2017 - Regular Activity in Midlife Spares Joints in Women
December 16, 2017 - Rain May Not Cause Achy Joints After All: MedlinePlus Health News
December 16, 2017 - MedDiet adherence doesn’t affect acute heart failure mortality
December 16, 2017 - HKBU experts develop new generation of smart anti-cancer drug molecules
December 16, 2017 - Chronic Kidney Disease Audit finds wide variations in coding of CKD patients in primary care
December 16, 2017 - Scientists use nanoparticles to fight Mucoviscidosis
December 16, 2017 - Increasing physical activity decreases risk of death from lymphoma
December 16, 2017 - Fear compromises the health, well-being of immigrant families, survey finds
December 16, 2017 - Rejected antibiotic candidate could be worth a second look, research finds
December 16, 2017 - Is Nation on the Right Track to Combat Opioid Crisis?
December 16, 2017 - Arthritis No Longer Just a Disease of the Old: MedlinePlus Health News
December 16, 2017 - Family members without inherited mutation have increased risk of melanoma
December 16, 2017 - Active surveillance proposed as first-line approach to manage patients with low-risk PMC of the thyroid
December 16, 2017 - Patients’ life values affect their attendance at medical treatment for pelvic-floor dysfunction
December 16, 2017 - Experts consider hazards of antibiotic resistances to be high
December 16, 2017 - Study finds erectile dysfunction as risk factor for early cardiovascular disease
December 16, 2017 - Amber-tinted glasses may reduce insomnia severity
December 16, 2017 - Arthritis Drug Seen Lowering GvHD Risk
December 16, 2017 - Atoh1, a potential Achilles’ heel of Sonic Hedgehog medulloblastoma
December 15, 2017 - Cornell engineers develop new method to measure vital signs using radio waves
December 15, 2017 - Rutgers studies highlight need for salon clients, workers to protect themselves from health risks
December 15, 2017 - FDA Approves Nucala (mepolizumab) for Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss Syndrome)
December 15, 2017 - Morning Break: CVS Buying Aetna; Uterus Transplant Baby; Your Brain on Drugs, Redux
December 15, 2017 - Social phobia linked to autism and schizophrenia
December 15, 2017 - Timestrip technology helping to prevent missed vaccinations
December 15, 2017 - Researchers win NIH grants for Alzheimer’s research on Amish resilience and rapid onset
December 15, 2017 - Mitochondrial error-correction mechanism essential for energy production of cells
December 15, 2017 - New report reveals steep rise in lung disease admissions to emergency departments during winter
December 15, 2017 - Study finds social stigma as barrier to successful treatment of children with HIV in Ethiopia
December 15, 2017 - Health Tip: Keep Gift-Giving Stress Under Wraps
December 15, 2017 - Long Stoppage of Bisphosphonates Tied to More Fractures
December 15, 2017 - Triglycerides Test: MedlinePlus Lab Test Information
December 15, 2017 - Study shows interventions, though few, can be effective for students with high-functioning autism
December 15, 2017 - Higher blood sugar during first trimester of pregnancy increases child’s risk of congenital heart defect
December 15, 2017 - Study tests accuracy of laboratory-developed cancer tests and FDA-approved companion diagnostics
December 15, 2017 - Extracellular vesicles can be used to effectively delay progression of kidney damage
December 15, 2017 - Targeted lung cancer treatments may benefit smokers and non-smokers alike
December 15, 2017 - Sugary-drink warning labels may help decrease obesity and overweight prevalence
December 15, 2017 - Coarse particulate matter exposure linked to increased asthma risk in children
December 15, 2017 - OCT Angio Gains Ground: Ophthalmology Times
December 15, 2017 - Flu Can Have Dangerous Domino Effect on Older Adults: MedlinePlus Health News
December 15, 2017 - A daily cup of hot tea may lower glaucoma risk
December 15, 2017 - New blood test accurately forecasts advanced heart failure patients’ survival after surgery
December 15, 2017 - Study finds improvements in survivals rates of individuals with kidney failure
December 15, 2017 - Rare gene mutation gives rise to low sensitivity to pain
December 15, 2017 - Older Women Do Well with New Breast Cancer Drugs
December 15, 2017 - Joint damage in healthy military recruits may mimic spondyloarthropathies
December 15, 2017 - Researchers examine link between tumor mutational burden and response to immune checkpoint therapy
December 15, 2017 - Nanotextured surfaces kill bacteria without harming mammalian cells
December 15, 2017 - Ketamine more effective than common sedative in reducing suicidal thoughts
December 15, 2017 - Scientists engineer light-emitting plant
December 15, 2017 - Medicare fails to recover hundreds of millions of dollars in lab overcharges
December 15, 2017 - IPM begins first clinical trial of vaginal rings to prevent HIV in women
December 15, 2017 - Telemedicine for addiction treatment? Picture remains fuzzy
December 15, 2017 - Genetic variations may help identify people at high-risk for chronic pain after surgery
December 15, 2017 - Intersect ENT Announces FDA Approval of Sinuva (mometasone furoate) Sinus Implant, a New In-Office Treatment Option for Recurrent Nasal Polyps
December 15, 2017 - Learning the Lessons of FluMist
December 15, 2017 - Study shows brain structures make some people resilient to Alzheimer’s disease
December 15, 2017 - UQ researchers create new and improved version of ‘love hormone’
December 15, 2017 - Anti-stress compounds provide new treatment approach for diabetes and obesity
December 15, 2017 - Survey finds extremely high rate of mortality from sepsis in ICUs
December 15, 2017 - Study provides insights into molecular mechanisms regulating cellular fate of SCCs
December 15, 2017 - Researchers identify previously unknown functions of natural killer cells in the womb
December 15, 2017 - Tech at Bedtime May Mean Heavier Kids
December 15, 2017 - Meta-Analysis: Hearing Loss Linked to Dementia in Elderly
December 15, 2017 - Second Phase 3 study results for LMTX published
December 15, 2017 - Researchers team up to identify vulnerabilities of lethal parasite
December 15, 2017 - Experts call for more action on gambling-related research and treatment
Potential new autism drug shows promise in mice

Potential new autism drug shows promise in mice

image_pdfDownload PDFimage_print

Scientists have performed a successful test of a possible new drug in a mouse model of an autism disorder. The candidate drug, called NitroSynapsin, largely corrected electrical, behavioral and brain abnormalities in the mice.

NitroSynapsin is intended to restore an electrical signaling imbalance in the brain found in virtually all forms of autism spectrum disorder (ASD).

“This drug candidate is poised to go into clinical trials, and we think it might be effective against multiple forms of autism,” said senior investigator Stuart Lipton, M.D., Ph.D., Professor and Hannah and Eugene Step Chair at The Scripps Research Institute (TSRI), who is also a clinical neurologist caring for patients.

The research, published on today in the journal Nature Communications, was a collaboration involving scientists at the Scintillon Institute; the University of California, San Diego School of Medicine; Sanford Burnham Prebys Medical Discovery Institute and other institutions. Lipton’s fellow senior investigators on the project were Drs. Nobuki Nakanishi and Shichun Tu of the Scintillon Institute in San Diego.

ASD is brain development disorder that affects 1 in 68 children in the United States alone. Because ASD has been diagnosed more often in recent years, most Americans now living with autism diagnoses are children—roughly 2.4 percent of boys and 0.5 percent of girls.

Genetic Analysis Leads to Potential Treatment

The new study stemmed from a 1993 study in which Lipton and his laboratory, then at Harvard Medical School, identified a gene called MEF2C as a potentially important factor in brain development.

This breakthrough led Lipton and colleagues to the discovery that disrupting the mouse version of MEF2C in the brain, early in fetal development, causes mice to be born with severe, autism-like abnormalities. Since that discovery in mice in 2008, other researchers have reported many cases of children who have a very similar disorder, resulting from a mutation to one copy of MEF2C (human DNA normally contains two copies of every gene, one copy inherited from the father and one from the mother). The condition is now called MEF2C Haploinsufficiency Syndrome (MHS).

“This syndrome was discovered in people only because it was first discovered in mice—it’s a good example of why basic science is so important,” Lipton said.

MEF2C encodes a protein that works as a transcription factor, like a switch that turns on the expression of many genes. Although MHS accounts for only a small proportion of autism disorder cases, large-scale genomic studies in recent years have found that mutations underlying various autism disorders frequently involve genes whose activity is switched on by MEF2C.

“Because MEF2C is important in driving so many autism-linked genes, we’re hopeful that a treatment that works for this MEF2C-haploinsufficiency syndrome will also be effective against other forms of autism,” Lipton said, “and in fact we already have preliminary evidence for this.”

For the study, the researchers created a laboratory model of MHS by engineering mice to have—like human children with MHS—just one functioning copy of the mouse version of MEF2C, rather than the usual two copies. The mice showed impairments in spatial memory, abnormal anxiety and abnormal repetitive movements, plus other signs consistent with human MHS. Analyses of mouse brains revealed a host of problems, including an excess in key brain regions of excitatory signaling (which causes neurons to fire) over inhibitory signaling (which suppresses neuronal activity).

In short, these two important kinds of brain signals were out of balance. A similar excitatory/inhibitory (E/I) imbalance is seen in most forms of ASD and is thought to explain many of the core features of these disorders, including cognitive and behavioral problems and an increased chance of epileptic seizures.

The researchers treated the MHS-mice for three months with NitroSynapsin, an aminoadamantane nitrate compound related to the Alzheimer’s FDA-approved drug memantine, which was previously developed by Lipton’s group. NitroSynapsin is known to help reduce excess excitatory signaling in the brain, and the team found that the compound did reduce the E/I imbalance and also reduced abnormal behaviors in the mice and boosted their performance on cognitive/behavioral tests—in some cases restoring performance essentially to normal.

Lipton and colleagues are currently testing the drug in mouse models of other autism disorders, and they hope to move NitroSynapsin into clinical trials with a biotechnology partner.

The work also has support from parents of children with MHS. “We are all hanging on to the hope that one day our children will be able to speak, to understand and to live more independent lives,” said Michelle Dunlavy, who has a son with MHS.

In fact, Lipton’s group is also now using stem cell technology to create cell-based models of MHS with skin cells from children who have the syndrome—and NitroSynapsin appears to work in this ‘human context’ as well. Dunlavy and other parents of children with MHS recently organized an international, Facebook-based support group, which is coordinating to assist in Lipton’s research going forward.

In an amazing twist, the scientific team also found in Alzheimer’s disease models that the new NitroSynapsin compound improves synapse function, the specialized areas for communication between nerve cells. Thus, the ability of the drug to improve ‘network’ communication in the brain may eventually lead to its use in several neurological diseases.


Explore further:
Breakthrough research suggests potential treatment for autism, intellectual disability

More information:
Shichun Tu et al, NitroSynapsin therapy for a mouse MEF2C haploinsufficiency model of human autism, Nature Communications (2017). DOI: 10.1038/s41467-017-01563-8

Journal reference:
Nature Communications

Provided by:
The Scripps Research Institute

Tagged with:

About author

Related Articles