Breaking News
January 19, 2019 - 4.6 percent of Massachusetts residents have opioid use disorder
January 19, 2019 - New study suggests vital exhaustion as risk factor for dementia
January 19, 2019 - New antibiotic discovery heralds breakthrough in the fight against drug-resistant bacteria
January 19, 2019 - Ural Federal University scientists synthesize a group of multi-purpose fluorophores
January 19, 2019 - Researchers identify new therapeutic target in the fight against chronic liver diseases
January 19, 2019 - Preparation, characterization of Soyasapogenol B loaded onto functionalized MWCNTs
January 19, 2019 - FDA Approves Ontruzant (trastuzumab-dttb), a Biosimilar to Herceptin
January 19, 2019 - Tobacco use linked with higher use of opioids and sedatives
January 19, 2019 - Study delves deeper into developmental dyslexia
January 19, 2019 - Anti-vaccination movement one of the top health threats in 2019 says WHO
January 19, 2019 - Newly developed risk score more effective at identifying type 1 diabetes
January 19, 2019 - Highly effective protocol to prepare cannabis samples for THC/CBD analysis
January 19, 2019 - Prinston Pharmaceutical Inc. Issues Voluntary Nationwide Recall of Irbesartan and Irbesartan HCTZ Tablets Due to Detection of a Trace Amount of Unexpected Impurity, N-Nitrosodiethylamine (NDEA) in the Products
January 19, 2019 - How does solid stress from brain tumors cause neuronal loss, neurologic dysfunction?
January 19, 2019 - $14.7 million partnership to supercharge vaccine development
January 19, 2019 - Ian Fotheringham receives Charles Tennant Memorial Lecture award
January 19, 2019 - Brain vital signs detect neurophysiological impairments in players with concussions
January 19, 2019 - Lack of job and poor housing conditions increased likelihood of people attending A&E
January 19, 2019 - Novel targeted drug delivery system improves conventional cancer treatments
January 19, 2019 - Rutgers study finds gene responsible for spread of prostate cancer
January 19, 2019 - Complications Higher Than Expected for Invasive Lung Tests
January 19, 2019 - 3-D printed implant promotes nerve cell growth to treat spinal cord injury
January 19, 2019 - Automated texts lead to improved outcomes after total knee or hip replacement surgery
January 19, 2019 - Poor cardiorespiratory fitness could increase risk of future heart attack, finds new study
January 19, 2019 - Drinking soft drinks while exercising in hot weather may increase risk of kidney disease
January 19, 2019 - Formlabs 3D prints anatomical models
January 19, 2019 - Heart-Healthy Living Also Wards Off Type 2 Diabetes
January 19, 2019 - Teaching Kids to Be Smart About Social Media (for Parents)
January 19, 2019 - Metabolite produced by gut microbiota from pomegranates reduces inflammatory bowel disease
January 19, 2019 - Researchers examine how spray from showers and toilets expose us to disease causing bacteria
January 19, 2019 - Behavioral experiments confirm that additional neurons improve brain function
January 19, 2019 - New study compares performance of real-time infectious disease forecasting models
January 19, 2019 - Obesity can be risk factor for developing renal cell carcinoma, confirms study
January 19, 2019 - New regulation designs on cigarette packs direct smokers’ attention to health warnings
January 19, 2019 - QIAGEN receives first companion diagnostic approval in Japan
January 19, 2019 - Study explores role of Dunning-Kruger effect in anti-vaccine attitudes
January 19, 2019 - Newly identified subset of immune cells may be key to fighting chronic inflammation
January 19, 2019 - New immune response regulators discovered
January 18, 2019 - Poor blood oxygenation during sleep predicts chance of heart-related death
January 18, 2019 - First international consensus on the diagnosis and management of fibromuscular dysplasia
January 18, 2019 - Rapid resistance gene sequencing technology can hasten identification of antibiotic-resistant bacteria
January 18, 2019 - Researchers develop artificial enzymatic pathway for synthesizing isoprenoids in E. coli
January 18, 2019 - Scientists advise caution in immunotherapy research
January 18, 2019 - How children across the world develop language
January 18, 2019 - Columbia Medical Student Receives McDonogh Scholarship
January 18, 2019 - Secretive ‘Rebate Trap’ Keeps Generic Drugs For Diabetes And Other Ills Out Of Reach
January 18, 2019 - Plant based diet could be the best option for the planet says commission
January 18, 2019 - New conservation practice could reduce nitrogen from agricultural drainage, study shows
January 18, 2019 - UIC researchers receive $1.7 million NCI grant to study Southeast Asian fruit
January 18, 2019 - New study determines the fate of DNA derived from genetically modified food
January 18, 2019 - Scientists develop new gene therapy that prevents axon destruction in mice
January 18, 2019 - Study finds critically low HPV vaccination rates among younger adolescents in the U.S.
January 18, 2019 - Brain cells involved in memory play key role in reducing future eating behavior
January 18, 2019 - Risk for Conversion of MS Varies With Different Therapies
January 18, 2019 - Investigational cream may help patients with inflammatory skin disease
January 18, 2019 - Medical school news office receives six writing awards | News Center
January 18, 2019 - County By County, Researchers Link Opioid Deaths To Drugmakers’ Marketing
January 18, 2019 - Research reveals risk for developing more than one mental health disorder
January 18, 2019 - Scientists discover a dramatic pattern of bone growth in female mice
January 18, 2019 - Study finds link between lengthy periods of undisturbed maternal sleep and stillbirths
January 18, 2019 - New nuclear medicine method could improve detection of primary and metastatic melanoma
January 18, 2019 - Combination therapy shows high efficacy in treating people with leishmaniasis and HIV
January 18, 2019 - Health Tip: Don’t Ignore Changes in Skin Color
January 18, 2019 - Dietary Recommendations for Healthy Children
January 18, 2019 - Eliminating the latent reservoir of HIV
January 18, 2019 - Pain From The Government Shutdown Spreads. This Time It’s Food Stamps
January 18, 2019 - Newly discovered regulatory mechanism helps control fat metabolism
January 18, 2019 - New rapid blood tests could speed up TB diagnosis, save the NHS money
January 18, 2019 - Researchers develop intelligent system for ‘tuning’ powered prosthetic knees
January 18, 2019 - Monoclonal antibody pembrolizumab prolongs survival in patients with squamous cell carcinoma
January 18, 2019 - Microrobots could one day deliver drugs inside the body
January 18, 2019 - Maintaining an active lifestyle in older age could prevent dementia
January 18, 2019 - New research detects mosquito known to transmit malaria for the first time in Ethiopia
January 18, 2019 - Researchers identify new genes linked to development of age-related macular degeneration
January 18, 2019 - Computerized method helps better protect pharma patents
January 18, 2019 - New guidelines to make swallowing safer for people in Australian nursing homes
January 18, 2019 - Lumex Instruments’ RA-915AM monitor installed at Hg treatment plant in Almadén, Spain
January 18, 2019 - ACCC survey finds multiple threats to growth of cancer programs
January 18, 2019 - Meeting the challenge of engaging men in HIV prevention and treatment
January 18, 2019 - Furloughed Feds’ Health Coverage Intact, But Shutdown Still Complicates Things
Newly developed drug compound may help treat Charcot-Marie-Tooth disease

Newly developed drug compound may help treat Charcot-Marie-Tooth disease

image_pdfDownload PDFimage_print

Scientists have developed a new drug compound that shows promise as a future treatment for Charcot-Marie-Tooth disease, an inherited, often painful neurodegenerative condition that affects nerves in the hands, arms, feet and legs. The researchers used the compound to treat the nerves of mice harboring the genetic defects that cause the disease.

The new study, from Washington University School of Medicine in St. Louis, challenges some conventional wisdom regarding how patients with this disease lose the ability to move their limbs.

The study appears April 20 in the journal Science.

Charcot-Marie-Tooth is the most common inherited degenerative disease of peripheral nerves. The disease affects about one in 2,500 individuals worldwide, and there are no treatments for it. The researchers studied a form of the condition called Charcot-Marie-Tooth disease type 2A, which is caused by specific genetic mutations.

These patients have inherited mutations that affect mitochondria, the energy factories of cells. Healthy mitochondria fuse together and exchange mitochondrial DNA. This healthy mitochondrial “sex” is impaired in this disease because of mutations in a protein called mitofusin2, which governs mitochondrial fusion.

Because they can’t fuse, the mitochondria of people with this disease appear small, granular and clumped when viewed under a microscope. Until now, the small size was thought to be the main problem in the disorder. Small energy factories can’t produce enough fuel to keep nerves alive, so the cells slowly die off, the thinking went. But senior author Gerald W. Dorn II, MD, the Philip and Sima K. Needleman Professor of Medicine, suspected something else was going on.

Dorn knew the genetic mutations in this disease aren’t confined to nerves; rather, they are present in all of the mitochondria in every cell of the body. Nerve cells and, for example, heart muscle cells burn energy at high rates and need healthy, robust mitochondria for fuel. A cardiologist by training, Dorn wondered why patients with the disease don’t have heart problems.

“This disease starts with nerve loss in the feet, moves up the legs, then to the arms, but it doesn’t have major effects elsewhere,” said Dorn, also director of the School of Medicine’s Center for Pharmacogenomics. “People with Charcot-Marie-Tooth eventually may need wheelchairs, but they have normal lifespans.

“We found that the problem isn’t mitochondria that are too small, but mitochondria that can’t travel distances. In heart cells, mitochondria are packed like sardines and don’t need to move much, so there’s no problem with energy supply,” he said. “But for mitochondria to make it down a person’s leg -; following the sciatic nerve from the lumbar spine to the foot -; that’s akin to a 500-mile trip. If a person can’t constantly renew mitochondria, over the years the nerves start to atrophy. Once the nerves die, the muscles atrophy as well.”

With distance identified as a key factor, the ideal animal model to study this disease, Dorn quipped, is the giraffe. But since that’s not an option and mice don’t develop symptomatic Charcot-Marie-Tooth (because mice are small and their mitochondria don’t have far to go), Dorn and his colleagues extracted sciatic nerves -; the longest nerve in the body -; from mice and set up a way to compare the speeds of mitochondria moving up and down the nerves.

Co-first author Antonietta Franco, PhD, a postdoctoral researcher, found that mitochondria in the mouse nerves with Charcot-Marie-Tooth type 2A mutations were almost static, moving very little in the time frame observed, even when sped up with time-lapse photography. In contrast, mitochondria moving along the nerve axons of normal mice, viewed under the same time-lapse conditions, resembled an aerial shot of a highway.

The researchers then added a drug compound to the nerves with the static mitochondria. This drug, which they designed, works something like a chemical key that unlocks mitofusin2 and boosts mitochondrial fusion. The work developing the drug compound was led by co-first author Agostinho G. Rocha, PhD, a staff scientist.

“After about 15 minutes of exposure to the compound, the mitochondrial traffic began to pick up,” Dorn said. “And after an hour, it looked like the normal nerve. We also found that the drug doesn’t have an effect when added to normal nerves. Mitochondria appear to have a speed limit.”

While the researchers know this drug boosts the ability of diseased mitochondria to fuse to one another, Dorn said it’s possible this is not what lets them move. It may be that the unlocked form of mitofusin2 also lets mitochondria couple to what Dorn calls the railroad tracks of cells. But more research is needed to answer that question.

Dorn said these findings may be relevant for other neurodegenerative disorders in which mitochondria are impaired, including other types of Charcot-Marie-Tooth disease.

Tagged with:

About author

Related Articles