Navigation Links
Better CMT outcome measurement is Wayne State University physician's goal

A Wayne State University physician is seeking a better way to determine the effectiveness of treatments for Charcot-Marie-Tooth disease (CMT), or inherited sensory-motor neuropathy, a disease that afflicts one in 2,500 people.

Sindhu Ramchandren, M.D., assistant professor of neurology in WSU's School of Medicine, believes the current lack of effective treatments for CMT may be because researchers are measuring the wrong outcomes. With a four-year, $661,000 Mentored Career Development Award from the National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health, she is working to develop an outcome measurement that accurately reflects CMT progression in children.

CMT refers to a heterozygous group of diseases caused by mutations in more than 50 genes. One of the most common genetic nerve diseases, it affects more than 120,000 Americans and causes progressive muscle weakness, painful foot deformities and walking difficulty.

As the disease progresses, weakness and muscle atrophy occur in the hands, resulting in difficulty with fine motor skills. Symptoms vary from patient to patient, with pain ranging from mild to severe. Some rely on foot or leg braces or other orthopedic devices to maintain mobility.

The identification of disease-causing genes has made the development of rational therapy a possibility in CMT. However, the lack of outcome measures to assess treatment effects in clinical trials is currently limiting therapeutic advances for CMT.

One of the most recent trials spanned several countries and involved ascorbic acid, or vitamin C, after animal models showed dramatic improvement in functioning.

"That gave a lot of hope to a lot of people," Ramchandren said.

One criticism of that group of trials is that they were rushed and used different outcome measures, but she said the rush was necessary because of the concern that CMT patients might medicate themselves with vitamin C in large quantities, and researchers wanted to see if the therapy actually was safe and effective in a randomized trial.

Trials in Australia, France, Italy, England and the Netherlands concluded that ascorbic acid, given as a medication, was safe but ineffective.

"One concern with those trials was that outcome measures varied," Ramchandren said. Some researchers measured a combined outcome score called the Charcot-Marie-Tooth Neuropathy Score, which was developed by Michael Shy, M.D., WSU professor of neurology and Ramchandren's mentor for her current study. Others looked at whether the speed of nerve conduction improved.

Because financial constraints typically limit trials to one or two years, Ramchandren said, an outcome measurement is needed that could change within that time period.

"A good outcome measure will show changes in scores in a short time period so that, when used in a trial, if a drug is effective, we should see those scores improve," she said. "However, if you use an outcome measure that barely budges in a short time period, there's not much chance you will get a dramatic improvement in scores, even if you have a good medication. So, with the recent CMT trials, it may very well be that vitamin C is ineffective, but we can't say for sure when there are doubts about what we are measuring."

With this grant, she will use data from an ongoing consortium study by Shy that collects natural history data on children and adult CMT patients to see how the disease progresses over time. Shy is mentoring Ramchandren as she develops a quality-of-life instrument to measure how CMT impacts children's lives.

Using a questionnaire format, Ramchandren will try to determine what kinds of physical activities CMT restrains. Questions also will address the disease's effects on social roles, such as playing with friends and interaction with families and teachers, as well as emotional behavior, depression and anger.

"We want something that enables children to tell us how this disease impacts their lives at any given point," she said. Questionnaires will be given to all children who come to Wayne State's CMT clinic through the consortium. Scores will be aligned with physical functioning and electrophysiologic studies to spot correlations between how patients feel they are doing and how the disease actually is impacting them neurophysiologically.

"We have shown that quality-of-life scores are low in children with CMT compared to healthy children," Ramchandren said. "We are hoping to show that if those scores change dramatically over the next two to three years, then quality of life might be an outcome measure that can be used in a clinical trial."

Such methodology has worked very well in cancer research, she said, where sometimes quality-of-life scores are first to improve, and then over time researchers see changes in tumor size or disease physiology. Ramchandren believes the same approach could be used for CMT and is working with mentor Lawrence Lum, M.D., professor of oncology at WSU and the Barbara Ann Karmanos Cancer Institute, on early phase clinical trial methodology training. Researchers there take bench work from animal models and translate it into new cancer therapies, she said.

Her eventual goal is to develop a clinical trials unit for all neuromuscular disorders, capable of translating promising animal research into new treatments.

Contact: Julie O'Connor
Wayne State University - Office of the Vice President for Research

Related biology news :

1. Aggression prevents the better part of valor ... in fig wasps
2. Researchers new recipe cooks up better tissue phantoms
3. Better batteries
4. Space shuttle data leads to better model for solar power production in California
5. More power to the cranberry: Study shows juice better than extracts at fighting infections
6. Children with certain dopamine system gene variants respond better to ADHD drug
7. Gene variant leads to better memory via increased brain activation
8. Better ways to predict kidney disease risk for African Americans
9. National labs leading charge on building better batteries
10. Better planning required if EU is to meet energy targets
11. Location matters: For invasive aquatic species, its better to start upstream
Post Your Comments:
(Date:11/4/2015)... 2015 --> ... by Transparency Market Research "Home Security Solutions Market - Global ... - 2022", the global home security solutions market is expected to ... The market is estimated to expand at a CAGR ... 2022. Rising security needs among customers at homes, the ...
(Date:10/29/2015)... 2015   MedNet Solutions , an innovative SaaS-based ... clinical research, is pleased to announce that it has ... as one of only three finalists for a ... and Growing" category. The Tekne Awards honor Minnesota ... technology innovation and leadership. iMedNet™ eClinical ...
(Date:10/29/2015)... 29, 2015 Daon, a global leader in ... released a new version of its IdentityX Platform ... North America have already installed IdentityX v4.0 ... a FIDO UAF certified server component as ... activate FIDO features. These customers include some of the ...
Breaking Biology News(10 mins):
(Date:12/1/2015)... , ... December 01, 2015 , ... ... announces Park NX10 SICM Module, an add-on scanning ion conductance microscopy module to ... of SICM to an AFM. , Park SICM benefits virtually all materials characterization ...
(Date:12/1/2015)... , December 1, 2015 Dr. Harry Lander , President ... serving as Chief Science Officer and recruits five ... Harry Lander , President of Regen, expands his role to ... recruits five distinguished scientists to join advisory team ... expands his role to include serving as ...
(Date:11/30/2015)... ... November 30, 2015 , ... Global Stem Cells Group announced ... new closed system for isolating adipose-derived stem cells. The announcement starts a new phase ... tissue. SVF is a component of the lipoaspirate obtained from liposuction of excess adipose ...
(Date:11/30/2015)... Partnership includes an MPP ... the u niversity , s Solid Drug Nanoparticle ... cale - up through cost ... , where licensees based anywhere in the world will have the right to ... Africa , where licensees based anywhere in the world will have the ...
Breaking Biology Technology: